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PubMed2005

The outcome of advanced or recurrent non-squamous carcinoma of the uterine cervix after platinum-based combination chemotherapy.

BACKGROUND: Data about the outcome and prognostic factors in the group of patients with non-squamous cell advanced or recurrent carcinomas of the uterine cervix are limited. We compared the outcome of patients with non-squamous with that of squamous cell carcinomas after platinum-based combination chemotherapy as first line therapy for stage IV or recurrent cervical carcinoma. PATIENTS AND METHODS: A total of 200 patients with stage IV or recurrent carcinomas of the cervix received platinum-based combination chemotherapy and were included in our analysis. RESULTS: There were 58 patients with non-squamous and 142 patients with squamous cell carcinomas. Response to chemotherapy was 53.5% in non-squamous vs. 43.5% in squamous carcinomas. Histology was not an independent predictor of tumor response (P = 0.797). Response rates were lower in patients with relapse only in a previously irradiated area in both squamous (26.9% vs. 53.5%, P = 0.005) and non-squamous carcinomas (47.1% vs. 65%, P = 0.270). Weight loss was the only significant predictor of survival in non-squamous histology patients (P < 0.0001). There was no significant difference in median survival between squamous (11.57 months [95% CI 9.35-13.79]) and non-squamous carcinomas (19.05 months [95% CI 13.63-24.47]) (P = 0.064). After adjustment for independent prognostic factors (ECOG performance status and weight loss), differences in survival remained not significant. CONCLUSION: Our study showed a similar outcome for both squamous and non-squamous stage IV or recurrent cervical carcinomas treated with platinum-based combination chemotherapy.

Adenocarcinoma↗

PubMed1997

Management of low-grade squamous intraepithelial lesions during pregnancy.

OBJECTIVE: Our purpose was to determine whether prenatal colposcopy is beneficial in pregnant women with squamous atypia, atypical squamous cells of undetermined significance, or low-grade squamous intraepithelial lesions on an initial screening Papanicolaou smear. STUDY DESIGN: A retrospective chart review identified a cohort of pregnant patients referred to the colposcopy clinic at Carolinas Medical Center between October 1991 and December 1994 with squamous atypia, atypical squamous cells of undetermined significance, or low-grade squamous intraepithelial lesions. Results of the colposcopic examination, cervical biopsy specimens, postpartum evaluation, and postpartum treatment were recorded. Descriptive statistics were used to tabulate numbers and percentages for all variables with 95% confidence intervals to determine disease progression. RESULTS: Prenatal colposcopy was performed on 253 women during the study period. The colposcopic impression was normal or consistent with low-grade squamous intraepithelial lesions in 235 (93%) of the women. Of the 67 women who had a cervical biopsy, 6 had a histologic diagnosis of high-grade squamous intraepithelial lesions. Postpartum Papanicolaou smears were obtained in 224 patients; 71 (32%) were normal, 145 (65%) were unchanged, and 8 (3%) showed high-grade squamous intraepithelial lesions. Of the 69 patients who had a postpartum cervical biopsy, 4 were found to have high-grade squamous intraepithelial lesions. Eight of the 10 women with biopsy-proved high-grade squamous intraepithelial lesions were compliant with treatment after delivery. Histologic examination of the cervix with tissue obtained by either loop conization or cold knife conization showed no evidence of invasive carcinoma. CONCLUSION: Squamous atypia, atypical squamous, cells of undetermined significance, or low-grade squamous intraepithelial lesions on a Papanicolaou smear in a pregnant patient does not require colposcopic evaluation during pregnancy. Progression of low-grade dysplasia to carcinoma during pregnancy is unusual, and no patient in this study was found to have invasive cancer.

Adolescent↗

PubMed1997

Correlation of regional formaldehyde flux predictions with the distribution of formaldehyde-induced squamous metaplasia in F344 rat nasal passages.

Squamous epithelium lines the nasal vestibule of the rat, rhesus monkey, and human. Respiratory, transitional, and olfactory epithelia line most areas posterior to the nasal vestibule. Inhaled formaldehyde gas induces squamous metaplasia posterior to the nasal vestibule and does not induce lesions in the nasal vestibule in rats and rhesus monkeys, indicating that squamous epithelium is resistant to irritant effects of formaldehyde and that squamous metaplasia may be an adaptive response. If squamous metaplasia is determined by formaldehyde dosimetry rather than by tissue-specific factors, squamous epithelium may be protective by absorbing less formaldehyde than other epithelial types. In a previous study, a three-dimensional, anatomically accurate computational fluid dynamics (CFD) model of the anterior F344 rat nasal passages was used to simulate inspiratory airflow and inhaled formaldehyde transport. The present study consisted of two related parts. First, the rat CFD model was used to test the hypothesis that the distribution of formaldehyde-induced squamous metaplasia is related to the location of high-flux regions posterior to squamous epithelium. Regional formaldehyde flux into nonsquamous epithelium predicted by the CFD model correlated with regional incidence of formaldehyde-induced squamous metaplasia on the airway perimeter of one cross-sectional level of the noses of F344 rats exposed to 10 and 15 ppm formaldehyde gas for 6 months. Formaldehyde flux into nonsquamous epithelium was estimated to vary by an order of magnitude depending on the degree of formaldehyde absorption by squamous epithelium. These results indicate that the degree to which squamous epithelium absorbs formaldehyde strongly affects the rate and extent of the progression of squamous metaplasia with continued exposure to formaldehyde. In the second part of this study, the CFD model was used to predict squamous metaplasia progression. Data needs for verification of this model prediction are considered. These results indicate that information on the permeability of squamous epithelium in rats, monkeys, and humans is important for accurate prediction of uptake in regions posterior to the nasal vestibule.

Administration, Inhalation↗

PubMed1997

Pulmonary cystic keratinizing squamous cell lesions of rats after inhalation/instillation of different particles.

Cystic keratinizing squamous cell lesions from three inhalation studies (Study A, B, C) and one intratracheal instillation study (Study D) in rats were reclassified and a certain number of lesions examined immunohistochemically for PCNA (proliferating cell nuclear antigen) as a marker of cellular proliferation. The following classification was used: squamous cell metaplasia with marked keratinization, keratinizing cyst, cystic keratinizing epithelioma, cystic keratinizing squamous cell carcinoma, keratinizing squamous cell carcinoma and non-keratinizing squamous cell carcinoma. In study A (inhalation of coal oven exhaust and subcutaneous injection of a high dose of DB (ah)A) 49.3% of rats developed cystic keratinizing squamous cell carcinomas. Inhalation of coal oven exhaust gas together with intratracheal instillation of crocidolite or subcutaneous injection of a low dose DB(ah)A (dibenz(ah)anthracene) resulted in cystic keratinizing squamous cell carcinomas in 23% to 24% of the rats. High incidences of cystic squamous cell carcinomas in the range of 31.9% to 76.4% were observed in rats of Study B1 after a 10-months exposure to tar/pitch condensation aerosol (different B(a)P (benzo(a)pyrene) concentrations) with added carbon black in some groups. After a 20-months exposure period to the same inhalation atmospheres (Study B2) the incidence of squamous cell carcinomas was increased up to 95.8%. Exposure of rats to various concentrations of unfiltered diesel exhaust (Study C) resulted in incidences of cystic keratinizing epitheliomas ranging from 2.5% (2.5 mg/m3) to 10.7% (7.5 mg/m3). Epitheliomas were also observed in 16.2% of carbon black and 16.0% of titanium dioxide exposed rats. Only a few cystic keratinizing squamous cell carcinomas occurred. In the intratrachel instillation study (Study D) increased incidences of cystic keratinizing epitheliomas occurred in rats exposed to native diesel exhaust particles (16.7%), high dose of extracted diesel exhaust particles (14.6%), extracted printex 90-carbon black particles (18.8%), and extracted printex 90-carbon black particles + B(a)P (18.8%). High indicences of cystic keratinizing squamous cell carcinomas were noted in rats that received 15 mg B(a)P (14.6%) or 30 mg B(a)P (72.7%) intratracheally. Immunohistochemical labeling of nuclei with PCNA demonstrated proliferative activity in one or two (and focally more than two) peripheral cell layers of cystic keratinizing epitheliomas and in more than three peripheral cell layers of cystic keratinizing squamous cell carcinomas and keratinizing squamous cell carcinomas. The wall of keratinizing cysts showed no or a weak reaction.

Administration, Inhalation↗

PubMed2000

Somatic mutations of Fas (Apo-1/CD95) gene in cutaneous squamous cell carcinoma arising from a burn scar.

Fas (Apo-1/CD95) is a cell-surface receptor involved in cell death signaling, and recent reports have suggested that defects within the Fas receptor pathway such as Fas mutation play an important part in the development and progression of human tumors. Burn scar-related squamous cell carcinoma of skin is a unique subtype of cutaneous squamous cell carcinoma, and tends to be more aggressive in nature than conventional squamous cell carcinoma. The molecular mechanisms underlying the development and progression of burn scar-related squamous cell carcinoma, however, are not clear. In this study, we analyzed the entire coding region and all splice sites of the Fas gene for the detection of the somatic mutations in a series of 50 conventional squamous cell carcinomas and 21 burn scar-related squamous cell carcinomas by polymerase chain reaction, single strand conformation polymorphism, and DNA sequencing. We detected mis-sense mutations in three of 21 burn scar-related squamous cell carcinomas (14.3%), whereas no mutation was detected in 50 conventional squamous cell carcinomas. Of the three Fas mutations detected in the burn scar-related squamous cell carcinomas, one was found in Fas ligand-binding domain, another one was identified in the death domain known to be involved in the transduction of an apoptotic signal, and the other one was found in the transmembrane domain. Our data show that some burn scar-related squamous cell carcinomas have Fas gene mutations in important regions for the apoptosis function and suggest that these mutations might be involved in the pathogenesis of burn scar-related squamous cell carcinomas. In addition, our results provide an important clue to understanding the difference between burn scar-related squamous cell carcinoma and conventional squamous cell carcinoma at the molecular level.

Adolescent↗

PubMed2002

Incidence and risk factors associated with a second squamous cell carcinoma or basal cell carcinoma in psoralen + ultraviolet a light-treated psoriasis patients.

Psoralen + ultraviolet A-treated psoriasis patients are at increased risk for squamous cell carcinomas and basal cell carcinomas; however, the incidence and risk factors associated with second squamous cell carcinomas and basal cell carcinomas in this population are not well qualified. Incidence and risk factors for second squamous cell carcinomas and basal cell carcinomas were studied in a cohort of 1380 psoralen + ultraviolet A-treated psoriasis patients prospectively followed for over 20 y; 264 had a squamous cell carcinoma and 258 a basal cell carcinoma after beginning psoralen + ultraviolet A therapy. After a first squamous cell carcinoma, the risk of a second squamous cell carcinoma was 26% at 1 y, 62% at 5 y, and 75% at 10 y. Risk increased with high psoralen + ultraviolet A exposure prior to the first squamous cell carcinoma (hazard ratio 3.32, 95% confidence interval 1.53, 7.18). Higher rates of post-first squamous cell carcinoma psoralen + ultraviolet A treatment also were associated with greater risk (hazard ratio 1.56 for every additional 10 treatments per year for patients with low pre-first squamous cell carcinoma psoralen + ultraviolet A exposure, 95% confidence interval 1.35, 1.81). Patients exposed to high levels of tar and/or ultraviolet B before a first squamous cell carcinoma were also at higher risk (hazard ratio 1.72, 95% confidence interval 1.14-2.60). Risk of a second basal cell carcinoma was 21% at 1 y, 49% at 5 y, and 61% at 10 y. There was some evidence that high exposure to psoralen + ultraviolet A before a first basal cell carcinoma was associated with increased risk of second basal cell carcinoma (hazard ratio 1.45, 95% confidence interval 0.97-2.17). Higher post-first tumor psoralen + ultraviolet A treatment rates also increased risk (hazard ratio 1.24 for every additional 10 treatments per year, 95% confidence interval 1.06-1.47). Psoralen + ultraviolet A-treated psoriasis patients appear to have a greatly increased incidence of second squamous cell carcinoma compared with the general population. Patients who develop a squamous cell carcinoma after starting psoralen + ultraviolet A therapy should be closely monitored for a subsequent squamous cell carcinoma.

Aged↗

PubMed2002

Association of multiple Lugol-voiding lesions with synchronous and metachronous esophageal squamous cell carcinoma in patients with head and neck cancer.

BACKGROUND: Patients with squamous cell carcinoma of the head and neck have a high prevalence of second primary esophageal squamous cell carcinomas. This study assessed the risk of developing second primary esophageal squamous cell carcinomas in patients with squamous cell carcinoma of the head and neck based on multiplicity of Lugol-voiding lesions observed by chromoendoscopy and patient characteristics. METHODS: Three hundred eighty-nine patients with newly diagnosed squamous cell carcinoma of the head and neck were divided into 4 groups: no Lugol-voiding lesions; several (</=10) small Lugol-voiding lesions; many (>10) small Lugol-voiding lesions; and many irregularly shaped, multiform Lugol-voiding lesions. Relative risk for the development of synchronous second primary esophageal squamous cell carcinomas was investigated by using univariate and multivariate analysis. Metachronous second primary esophageal squamous cell carcinomas was also studied among 227 patients followed more than 1 year after initial examination. RESULTS: Fifty-four (14%) of the 389 patients were found to have synchronous second primary esophageal squamous cell carcinomas. In particular, 55% of the patients with many irregular-shaped multiform Lugol-voiding lesions had synchronous second primary esophageal squamous cell carcinomas. Univariate analysis showed that the presence of many irregular-shaped multiform Lugol-voiding lesions, drinking habit, male gender, and smoking were significant risk factors for the development of synchronous second primary esophageal squamous cell carcinomas. Multivariate analysis also revealed that many irregular-shaped multiform Lugol-voiding lesions (odds ratio: 21.4; p < 0.001) and drinking habit (odds ratio: 3.3; p < 0.02) were independent risk factors. During follow-up, 7 patients (3%) had metachronous second primary esophageal squamous cell carcinomas; 6 had many irregular-shaped multiform Lugol-voiding lesions and the seventh had many small Lugol-voiding lesions in the background mucosa. CONCLUSIONS: The presence of numerous irregular-shaped multiform Lugol-voiding lesions was closely associated with second primary esophageal squamous cell carcinomas in patients with squamous cell carcinoma of the head and neck. This might be explained by the concept of "field cancerization." Ingestion of alcohol may play an important role in the occurrence of this phenomenon.

Adult↗

PubMed1995

High frequency of chromosome 9p allelic loss and CDKN2 tumor suppressor gene alterations in squamous cell carcinoma of the bladder.

BACKGROUND: In the Western Hemisphere, 90% of bladder cancers are transitional cell carcinomas, while only 7% are classified as squamous cell carcinomas. In contrast, in Egypt and regions of the Middle East and Africa, where infection by the trematode Schistosoma haematobium is endemic, squamous cell carcinoma is the most common bladder cancer as well as the most common cancer in men. PURPOSE: We planned experiments to understand the genetic defects underlying the development of squamous cell carcinoma and to determine if the morphologically and clinically distinct squamous cell carcinoma and transitional cell carcinoma of the bladder evolve following different genetic alterations. METHODS: Squamous cell carcinoma specimens from high-risk (Egypt, n = 19) and low-risk (Sweden, n = 12) populations were examined for genetic defects known to be involved in transitional cell carcinoma tumorigenesis. Homozygous deletions of the CDKN2 tumor suppressor gene were detected by comparative multiplex polymerase chain reaction. Mutations in the CDKN2 and p53 (also known as TP53) genes were analyzed by single-strand conformation polymorphism and DNA sequencing. Immunohistochemical staining of p53 protein was also performed. Allelic losses in chromosome arms 9p, 9q, and 17p were determined by microsatellite analysis. RESULTS: Homozygous deletions and sequence mutations in the CDKN2 gene were found in 67% (eight of 12) of squamous cell carcinoma specimens, a frequency three times higher than that reported for uncultured transitional cell carcinomas (P = .009). Hemizygous and homozygous deletions in 9p, where CDKN2 resides, were found in 92% (11 of 12) of uncultured squamous cell carcinomas, while only about 39% (35 of 90) of transitional cell carcinomas showed these losses (P = .001). Deletions in 9p with no change in 9q were found in 92% (10 of 11) of squamous cell carcinomas compared with only 10% (11 of 110) of transitional cell carcinomas (P < .001) reported in the literature. The frequency of p53 mutations in squamous cell carcinomas was similar to that reported for invasive transitional cell carcinomas (60%), but the type and position of mutations differed between the two tumor types. Allelic losses in chromosome arm 17p, where the p53 gene resides, were found to be less frequent in squamous cell carcinomas (38%) than in invasive transitional cell carcinomas (60%). CONCLUSIONS: Our results suggest that a putative tumor suppressor gene on 9p, possibly CDKN2, may contribute to squamous cell carcinoma tumorigenesis. Our data on squamous cell carcinoma and previously reported data on transitional cell carcinoma indicate that these two bladder carcinomas differ in their genetic alterations, suggesting that distinct underlying genetic defects may explain, at least in part, the pathological differences between the two tumors of the bladder epithelium. IMPLICATIONS: Development of diagnostic and therapeutic strategies for squamous cell carcinoma of the bladder based on its distinct genetic alterations is warranted.

Alleles↗

PubMed2004

Basaloid squamous cell carcinoma of the head and neck.

PURPOSE OF REVIEW: Basaloid squamous cell carcinoma is an uncommon variant of squamous cell carcinoma and was first described as a distinct entity in 1986. Basaloid squamous cell carcinoma seems to have a poorer survival rate than classical squamous cell carcinoma. On the basis of a critical literature survey, we attempt to evaluate if basaloid squamous cell carcinoma is really more aggressive and presents a poorer outcome than squamous cell carcinoma. RECENT FINDINGS: All papers are retrospective, and most include small numbers of cases, which are further diminished when subdivided according to specific sites. Only in three studies was basaloid squamous cell carcinoma of the head and neck region compared with matched squamous cell carcinoma controls. These studies did not show a uniform tendency regarding the aggressiveness and outcome of basaloid squamous cell carcinoma. In addition, several recent papers confirmed the presumed greater aggressiveness and worse outcome, and other recent papers questioned these characteristics. SUMMARY: The presented literature survey does not permit conclusions regarding the aggressiveness and outcome of basaloid squamous cell carcinoma compared with squamous cell carcinoma. Greater numbers of basaloid squamous cell carcinoma should be studied and compared with site-matched, stage-matched, and age-matched controls of conventional squamous cell carcinoma.

Carcinoma, Squamous Cell↗

PubMed1998

Inter- and intra-observer variation in the histopathological reporting of cervical squamous intraepithelial lesions using a modified Bethesda grading system.

OBJECTIVE: 1. To assess inter- and intra-observer variation in the histopathological reporting of cervical colposcopic biopsies using a histologic modification of the cytological Bethesda grading system; 2. to determine the histologic profile of those cases which resulted in diagnostic disagreement. METHODS: Consecutive cervical colposcopic biopsies (n = 125) were assessed independently by six experienced histopathologists. Cases were classified as normal, low grade squamous intraepithelial lesion or high grade squamous intraepithelial lesion. Six months later the process was repeated. The degree of inter and intra-observer variation was assessed by kappa statistics. All cases in which there was less than perfect inter and intra-observer agreement were reviewed by the coordinator of the study. RESULTS: In the first round of the study inter-observer agreement was generally poor, with unweighted and weighted kappa values ranging from 0.15 to 0.58 (average 0.30) and from 0.21 to 0.61 (average 0.36) respectively. In the second round inter-observer agreement was better, with unweighted and weighted kappa values ranging from 0.08 to 0.55 (average 0.33) and from 0.22 to 0.59 (average 0.42). Ten of the 15 pairs of observers achieved fair inter-observer agreement using weighted kappa analysis. The degree of intra-observer agreement was better, unweighted and weighted kappa values ranging from 0.26 to 0.61 (average 0.47) and from 0.34 to 0.62 (average 0.51) respectively. Two of the six participants achieved fair intra-observer agreement and two achieved good intra-observer agreement using weighted kappa analysis. There were marked difficulties in the separation of normal squamous epithelium from low grade squamous intraepithelial lesion and in the separation of low grade from high grade squamous intraepithelial lesions. Histopathological review revealed that many of the difficulties in the separation of normal and low grade squamous intraepithelial lesion were in the distinction between superficial vacuolated cells and true koilocytes. Difficulties also resulted in the separation of basal cell hyperplasia, inflammatory associated changes and immature squamous metaplasia from low grade squamous intraepithelial lesion. Conditions which resulted in difficulty in the separation of low grade and high grade squamous intraepithelial lesions included florid koilocytotic change and immature metaplastic squamous epithelium with atypia. In some cases, there was a full spectrum of diagnoses from normal to high grade squamous intraepithelial lesion. These were largely cases of immature metaplastic squamous epithelium with atypia and of thin or atrophic squamous epithelium with atypia. CONCLUSIONS: Most pairs of observers can achieve fair inter-observer agreement in the reporting of cervical colposcopic biopsies using a modified Bethesda system. Intra-observer agreement is also generally fair to good using this system. It may be that a two tier grading system is more appropriate for the histopathological reporting of these biopsies than the traditional three-tier intraepithelial neoplasia (CIN) system.

Biopsy↗

PubMedDate not supplied

Gene expression of human squamous cell carcinoma antigens 1 and 2 in human cell lines.

The squamous cell carcinoma antigen (SCCA) serves as a serological marker for squamous cell carcinomas. Molecular cloning of the SCCA genomic region has revealed the presence of two tandemly arrayed genes, SCCA1 and SCCA2. SCCA1 is a papain-like cysteine proteinase inhibitor, while SCCA2 is a chymotrypsin-like serine proteinase inhibitor. Little is known concerning how expression of the SCCA1 and SCCA2 genes is regulated in human cell lines. The purpose of this study was to determine whether the SCCA1 gene or SCCA2 gene is more strongly expressed in human cell lines. Squamous cell carcinoma cell lines secreted respectively 4 times and 50 times as much SCCA proteins into medium as normal human keratinocyte and non-squamous cell carcinoma cell lines, as measured by enzyme-linked immunosorbent assay. Quantitative RT-PCR ELISA digoxigenin-labeling assay demonstrated that SCCA1 mRNA expression in squamous cell carcinoma cell lines was respectively 2.8 times and 42 times that in keratinocyte and non-squamous cell carcinoma cell lines. The ratio of SCCA1 to SCCA2 mRNA expression differed distinctly among squamous cell carcinoma, keratinocyte and non-squamous cell carcinoma cell lines (2.8, squamous; 24.1, keratinocyte; 11.0, non-squamous). These findings suggest that SCCA1 is mainly expressed in squamous cell carcinoma, keratinocyte and non-squamous cell carcinoma cell lines and that the ratio of SCCA1 to SCCA2 expression might be a novel marker for the detection of squamous cell carcinoma.

Adenocarcinoma↗

PubMed1988

Squamous differentiation in carcinoma of the endometrium: a critical appraisal of adenoacanthoma and adenosquamous carcinoma.

Although squamous differentiation within endometrial carcinomas has long been recognized by pathologists, its biologic significance has been the subject of continued debate. While some authors have found a worsened prognosis for women who have tumors with squamous elements, others have reported the prognosis to be better than conventional endometrial adenocarcinomas. Persisting confusion and disagreement about the use of the terms adenoacanthoma and adenosquamous carcinoma have complicated the issue. In this article we review the literature on the pathogenesis of squamous differentiation in the endometrium and discuss the histologic features, prevalence, and biologic behavior of adenocarcinoma with squamous differentiation. We conclude that keratin is a constituent of normal and neoplastic endometrial epithelial cells, and that overt squamous differentiation occurs by a mechanism that is currently unknown. Squamous differentiation is present in about 25% of endometrial adenocarcinomas, a frequency that appears to have been constant for the past 50 years. The squamous component of endometrial carcinomas may histologically appear benign, malignant, or indeterminant, and in the majority of instances closely parallels the differentiation of the glandular component. Endometrial adenocarcinomas with malignant-appearing squamous elements usually have poorly differentiated glandular components and have a prognosis identical to that of poorly differentiated adenocarcinoma without squamous differentiation. Endometrial adenocarcinomas with benign-appearing squamous elements are usually associated with well-differentiated glandular components and have a prognosis identical to that of typical well-differentiated adenocarcinoma. Some endometrial adenocarcinomas contain foci of squamous differentiation that appear neither clearly benign nor malignant. These often are associated with moderately differentiated glandular components; the prognosis for these women is not yet clearly defined. At the present time we are unable to attribute any prognostic significance to the presence of squamous differentiation in endometrial carcinomas. Because of the confusion and semantic arguments that revolve about the use of the terms adenoacanthoma and adenosquamous carcinomas, we recommend that those terms be abandoned and be replaced by the single term adenocarcinoma with squamous differentiation. As for any other endometrial tumor, the pathologist should provide information on histological grade, depth of myometrial invasion, and presence of vascular involvement or spread to the cervix in order to guide the gynecologist in determining appropriate therapy.

Adenocarcinoma↗

PubMed1998

Comparison of estrogen and progesterone receptor, Ki-67, and p53 immunoreactivity in uterine endometrioid carcinoma and endometrioid carcinoma with squamous, mucinous, secretory, and ciliated cell differentiation.

An analysis of 77 uterine endometrioid carcinomas was performed to compare pure endometrioid carcinomas and endometrioid carcinomas with various types of cellular differentiation for the expression of estrogen (ER) and progesterone (PR) receptors, p53, and Ki-67 and to correlate these findings with clinicopathologic features. Forty-three pure endometrioid carcinomas and 34 endometrioid carcinomas displaying additional types of cellular differentiation in at least 10% of the tumor (16 squamous, 11 mucinous, four ciliated cell, and three secretory) were analyzed. In 8 of the 16 tumors with squamous differentiation, the squamous component was histologically benign (low grade), and in eight tumors it was histologically malignant (high grade). In tumors showing various types of cellular differentiation except those with a high-grade squamous component, comparison of the endometrioid glandular component with the squamous, mucinous, secretory, and ciliated cell components showed that ER/PR, Ki-67, and p53 expression were generally higher in the glandular component compared with the various differentiated components. These findings parallel the changes that occur in the endometrium in the secretory phase of the menstrual cycle and, therefore, suggest that the differentiated components have undergone terminal differentiation. In contrast, in endometrioid carcinomas with a high-grade squamous component, Ki-67 and p53 expression were the same in the glandular and squamous components suggesting that squamous epithelium in these tumors represented another pathway of cellular differentiation but not one that was terminally differentiated. Endometrioid carcinomas with a high-grade squamous component had significantly higher grade (P = .002), stage (P < .001), cellular proliferation index (P = .0005), and worse outcome (P = .0009) compared with tumors with the other types of cellular differentiation, including those with a low-grade squamous component and pure low-grade endometrioid carcinomas. In addition, carcinomas with a high-grade squamous component occurred in older women and were more frequently associated with atrophic endometrium and less replacement hormone therapy, but the differences were not statistically significant. In conclusion, endometrioid carcinomas with various types of cellular differentiation can be broadly divided into two groups. Tumors with mucinous, secretory, and ciliated cell differentiation and those with a low-grade squamous component are similar to pure low-grade endometrioid carcinomas in that most have high ER and PR expression, low cellular proliferation indices, low p53 immunoreactivity, and good prognosis. In contrast, endometrioid carcinomas with a high-grade squamous component lack expression of ER and PR, have high cellular proliferation indices, often express p53, and have a prognosis similar to poorly differentiated endometrioid carcinomas.

Adult↗

PubMed2001

Increased telomerase activity and elevated hTERT mRNA expression during multistage carcinogenesis of squamous cell carcinoma of the lung.

BACKGROUND: Telomerase activation is believed to play a critical role in the immortalization of cells and carcinogenesis. Telomerase activity is undetectable in normal somatic cells (except for those cells undergoing proliferation) but is expressed in the majority of human tumors including lung carcinoma. The expression of hTERT mRNA has been found to be correlated with telomerase activity. In the current study, the authors analyzed telomerase activity and hTERT mRNA expression in preinvasive bronchial lesions using biopsy specimens obtained by fluorescence bronchoscopy. METHODS: The authors studied 150 bronchial biopsy specimens obtained by fluorescence bronchoscopy. The intensity of telomerase activity was determined by the fluorescence-based telomeric repeat amplification protocol method in 74 bronchial biopsy specimens (22 normal bronchial epithelium or bronchitis cases, 15 squamous metaplasia cases, 23 dysplasia cases, and 14 squamous cell carcinoma cases), and the level of hTERT mRNA was analyzed in another 76 specimens (24 normal bronchial epithelium or bronchitis cases, 15 squamous metaplasia cases, 20 dysplasia cases, and 17 squamous cell carcinoma cases) by real-time polymerase chain reaction. RESULTS: The mean values (+/- the standard deviation [SD]) of telomerase activity in normal bronchial epithelium or bronchitis, squamous metaplasia, dysplasia, and squamous cell carcinoma cases were 6.2 +/- 7.5, 13.9 +/- 14.8, 18.5 +/- 20.8, and 54.5 +/- 22.3 U/microg protein, respectively. The upper limit of telomerase activity in normal bronchial epithelium or bronchitis was 21 U/microg protein (mean + 2SD). It is interesting to note that, 5 of 15 squamous metaplasia biopsies (33%), 8 of 23 dysplasia biopsies (35%), and all squamous cell carcinoma biopsies (100%) exhibited levels of telomerase activity that were > 21 U/microg protein. The mean levels of hTERT mRNA in normal bronchial epithelium or bronchitis, squamous metaplasia, dysplasia, and squamous cell carcinoma cases were 891 +/- 840, 1936 +/- 1704, 3019 +/- 2607, and 12965 +/- 18008 copies/microg total RNA, respectively. Telomerase activity and hTERT mRNA expression were found to increase in proportion to the severity of histologic change from normal bronchial epithelium or bronchitis to squamous cell carcinoma. CONCLUSIONS: These results suggest that an increase in telomerase activity and hTERT mRNA expression are features of the early stages of the development of squamous cell carcinoma of the lung, with strong telomerase activity and hTERT mRNA expression being prominent during the latter stages.

Adult↗

PubMed2002

Pagetoid variant of actinic keratosis with or without squamous cell carcinoma of sun-exposed skin: a lesion simulating extramammary Paget's disease.

BACKGROUND: Extramammary Paget's disease usually occurs in anogenital skin. We present five cases of squamous cell carcinoma in situ of sun-exposed skin and non-squamous cell carcinoma in situ actinic keratosis that displayed atypical keratinocytes disposed in intraepithelial cell nests and immunohistochemical staining simulating extramammary Paget's disease. METHODS AND RESULTS: Two pilot cases--one squamous cell carcinoma in situ and one non-squamous cell carcinoma in situ actinic keratosis with formation of intra-epidermal nests of atypical keratinocytes with a pagetoid spread pattern--were encountered at our institution. Fifty-four consecutive cases of squamous cell carcinoma in situ including bowenoid actinic keratosis and 34 cases of non-squamous cell carcinoma in situ actinic keratosis were reviewed to identify pagetoid spread of atypical cells. Representative sections of all cases with pagetoid spread of atypical keratinocytes were submitted for special stains for mucin, and immunostaining for cytokeratin 7 (CK7), cytokeratin 20 (CK20), cytokeratin CAM 5.2 (CAM 5.2), carcinoembryonic antigen (CEA), vimentin and S100 protein. In the group of squamous cell carcinoma in situ, 10 cases displayed pagetoid spread of atypical keratinocytes with cytoplasm ranging from clear to pale and atypical hyperchromatic nuclei. One review squamous cell carcinoma in situ was multicentric with three separate lesions. The atypical keratinocytes tended to form well to poorly defined cell groups extending from the basal cell layer to the corneal layer. No similar cases were identified in the group of non-squamous cell carcinoma in situ actinic keratosis. Two pilot cases and three of 10 review cases with a total of seven separate lesions displayed a moderate to marked immunohistochemical reactivity for CK7 similar to extramammary Paget's disease. CEA immunoreactivity was also detected in two of these cases. In addition, two of 44 squamous cell carcinomas in situ without pagetoid spread of atypical keratinocytes showed a moderate reactivity for CK7 in very occasional atypical keratinocytes. The remaining seven squamous cell carcinomas in situ with pagetoid spread of atypical keratinocytes were not immunoreactive for CEA and CK7. Immunostaining for CK20, vimentin, S100 protein was negative in all atypical cells in all study cases. CONCLUSIONS: Actinic keratosis, particularly squamous cell carcinoma in situ of sun-exposed skin, may have histopathological and immunohistochemical features similar to extramammary Paget's disease and probably represents a variant of actinic keratosis. Awareness of the pagetoid variant of actinic keratosis arising in sun-exposed skin is helpful to avoid the over-diagnosis of extramammary Paget's disease.

Adult↗

PubMed1991

Probable nonpapillomavirus etiology of squamous cell carcinoma of the vulva in older women: a clinicopathologic study using in situ hybridization and polymerase chain reaction.

A clinical, pathologic, and molecular virologic analysis of 30 cases of invasive squamous cell carcinoma of the vulva was undertaken to investigate the relationship of human papillomavirus (HPV) to this neoplasm. The presence of the virus was detected by the polymerase chain reaction and localized in the tumor and in the adjacent epithelium by in situ hybridization of paraffin sections of vulvectomy specimens. Specimens were examined for nucleic acid sequences of HPVs 6, 11, 16, and 18 were detected by in situ hybridization utilizing 35S-labeled antisense RNA probes and by polymerase chain reaction using HPV type-specific primers for a segment of the E6 gene followed by Southern hybridization of the amplified products. The cases were classified as typical squamous cell carcinoma, basaloid carcinoma, and warty carcinoma. Typical squamous cell carcinoma shows varying degrees of squamous maturation, whereas basaloid carcinoma is characterized by immature basal-type cells showing minimal or no squamous maturation. Warty carcinoma displays an exophytic condylomatous appearance. The squamous cells of this tumor are mature, and many show koilocytotic atypia characterized by a variable degree of nuclear atypia and cytoplasmic vacuolization. The adjacent epithelium was classified as squamous hyperplasia, lichen sclerosus, or vulvar intraepithelial neoplasia (VIN). VIN was subdivided into basaloid or warty VIN using similar criteria as for the invasive carcinomas. Overall, HPV 16 was detected in 11 cases and HPV 18 in two; none of the cases were positive for HPVs 6/11. HPV was detected in four (21%) of 19 squamous cell carcinomas, six (75%) of eight basaloid carcinomas, and three (100%) of three warty carcinomas. The adjacent epithelial lesions also showed a close correlation with the tumor type and presence of HPV. Fourteen (74%) squamous cell carcinomas had adjacent squamous hyperplasia; all of these squamous hyperplasias were negative for HPV. In contrast, seven (87%) of the basaloid carcinomas had adjacent basaloid-VIN and HPV 16 was detected within the VIN in three. Three warty carcinomas (100%) had adjacent warty VIN or basaloid VIN, and HPV was detected within VIN in two. The mean age of women with squamous cell carcinoma was 77 years, for women with basaloid carcinoma 54 years, and for those with warty carcinoma 47 years. The mean age of women with HPV-negative tumors was 77 years compared with 55 years for women with HPV-positive tumors (p less than 0.01). Thus, there appears to be a close correlation between the presence of HPV, specific subsets of invasive carcinoma and VIN, and age.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗

PubMed1996

The many faces of squamous cell carcinoma.

BACKGROUND: Cutaneous squamous cell carcinoma is a disease that has a multitude of clinical, histologic, and etiologic subtypes, all of which are of significance to the clinician. OBJECTIVE: Ten of the most common and clinically significant subtypes of squamous cell carcinoma are presented to emphasize the clinical importance of each and to emphasize and contrast their differences. METHODS: The literature of each subtype of squamous cell carcinoma is reviewed and capsulized. RESULTS: Appropriate diagnosis, therapy, and postoperative management of all subtypes of squamous cell carcinomas are dependent upon the understanding of their unique characteristics. CONCLUSION: The 10 common variants of squamous cell carcinoma presented in this paper: neurotrophic squamous cell carcinoma, Bowen's disease, squamous cell carcinoma in transplant patients, keratoacanthoma-like squamous cell carcinoma, squamous cell carcinoma of the lip, adenoid squamous cell carcinoma, spindle cell squamous cell carcinoma, radiation-induced squamous cell carcinoma, verrucous carcinoma, and Marjolin's ulcer, have unique etiologic, histologic, and clinical features that significantly influence their diagnosis, treatment, and subsequent management. It is imperative that physicians responsible for the care of these patients understand the implication of these unique characteristics.

Carcinoma, Squamous Cell↗

PubMed1998

Patterns of expressions of transforming growth factor and epidermal growth factor receptor in squamous cell lesions of the urinary bladder.

AIM: To investigate the patterns of expression of transforming growth factor alpha (TGF-alpha) and epidermal growth factor receptor (EGFR) in squamous metaplasia and squamous cell carcinomas of the urinary bladder with and without schistosomiasis. METHODS: Immunohistochemical study of the expression of TGF-alpha and EGFR in squamous metaplasias (n = 12) and various grades of squamous cell carcinomas (n = 21) of the bladder with and without schistosomiasis. RESULTS: Focal cytoplasmic and membranous positivity for EGFR and TGF-alpha was seen in all cases of squamous metaplasia. The markers were diffusely coexpressed in a concordant pattern in areas of hyperplastic keratinising squamous metaplasia. A similar pattern of positivity was seen in verrucous carcinomas (n = 2) and well differentiated squamous carcinomas (n = 6). Progressive loss of differentiation was associated with increasing loss of EGFR staining while TGF-alpha staining was retained. Squamous cell carcinoma in situ (n = 2) showed focal positivity for TGF-alpha and EGFR. There were no differences in staining patterns between cases with and without schistosomiasis. CONCLUSIONS: The coexpression of TGF-alpha and EGFR by well differentiated squamous cell carcinomas and hyperplastic keratinising squamous metaplasia is consistent with the active regulatory role exerted by this autocrine loop. There is regional absence of expression of EGFR but not of TGF-alpha in squamous cell carcinomas of lesser differentiation, suggesting heterogeneity of such control in these tumours. The focal expression of the two markers in squamous cell carcinomas in situ indicates a possible second pathway of oncogenesis for less differentiated tumours. These observations may have important implications for the effectiveness of putative growth factor based treatments.

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