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PubMed1998

Correlation between HPV types associated with oral squamous cell carcinoma and cervicovaginal cytology: An in situ hybridization study.

Epidemiologic and clinical evidence suggests a possible relationship between the human papillomavirus types found in oral squamous cell carcinoma and cervicovaginal cancer. To try to address this question, we analyzed by in situ hybridization 50 paraffin-embedded biopsies of oral squamous cell carcinomas and their corresponding Papanicolaou smears using nonradioactive DNA probes for human papillomavirus type 6/11 and 16/18. This analysis revealed that 70% (35 of 50) of oral squamous cell carcinomas and 56% (28 of 50) of Papanicolaou smears were positive for one or both of these human papillomavirus DNA probes. In 23 of the 28 patients who were positive for human papillomavirus sequences in the cervicovaginal tract, we found the same human papillomavirus type in the oral cavity. Five of the positive in situ hybridization Papanicolaou smears were associated with negative in situ hybridization oral squamous cell carcinomas. Our data suggest that after a primary infection by human papillomavirus, other mucosal sites may eventually become infected. Local environmental factors may contribute to the pathogenesis of lesions such as oral squamous cell carcinoma.

Adult↗

PubMedDate not supplied

Squamous cell carcinoma of the pancreas.

Squamous cell carcinoma of the pancreas is a controversial entity. Although some reports show that it is metastatic from another source, others demonstrate that it is a primary tumor. Between 1988 and 1997, fourteen cases of pancreatic squamous cell carcinoma were identified in the records of our pathology department. In seven instances the features were consistent with squamous cell carcinoma with no adenomatous component. The records of six of these patients were available for review and constitute the basis for this report. Five patients were diagnosed by means of percutaneous CT-guided fine-needle aspiration, whereas the sixth patient was diagnosed using a transduodenal core needle biopsy. At the time of diagnosis four patients had lung lesions, three patients had liver lesions, and two patients had lytic bone lesions. One patient had a 6 cm esophageal lesion. Surgical intervention had no impact on treatment or palliation in one of the patients. Chemotherapy and radiation therapy, alone or in combination, were ineffective in all patients. Median survival from the time of diagnosis was 2 months. We conclude that in cases of squamous cell carcinoma of the pancreas, every effort should be made to exclude adenomatous components histologically within the tumor and to exclude another primary source of squamous cell carcinoma. This will allow a better understanding of this entity and a refinement of therapy.

Adult↗

PubMed2000

Epstein-Barr virus in squamous carcinoma of the anterior nasal cavity.

Squamous carcinoma is the most common malignancy of the head and neck, but it rarely occurs in the nasal vestibule. Epstein-Barr virus (EBV) has been detected in and is causally linked to various head and neck tumors, particularly nasopharyngeal carcinoma. The possible role of EBV in squamous carcinoma of the anterior nasal cavity, particularly of the nasal vestibule, has not been previously investigated. Histologic sections from 17 patients with nasal vestibular squamous carcinoma were examined. Material for EBV detection by immunohistochemistry and by in situ hybridization was available in 15 of the 17 cases. The study group consisted of eight men and nine women ranging in age from 40 to 82 years (mean age, 64 years). None of the patients was of Asian descent. The squamous carcinomas were graded as well differentiated (one case), moderately differentiated (11 cases), and poorly differentiated (five cases). Fourteen patients were smokers; the history of smoking ranged from 20 to 60 pack-years. Treatment modalities included surgical resection, radiation, chemotherapy, or a combined approach. The clinical follow-up periods ranged from 7 months to 16 years. Three patients developed metastases, one of whom died of disease after 1 year. Epstein-Barr virus was not detected in any of the 15 of 17 cases tested by either immunohistochemistry or by in situ hybridization. Squamous carcinoma of the nasal vestibule is an uncommon cancer that is not causally related to EBV.

Adult↗

PubMed1999

Squamous metaplasia of the bladder: findings in 14 patients and review of the literature.

We have documented the data of squamous metaplasia of the bladder in 14 patients who had undergone cystoscopies for different reasons. In two biopsies, there were marked keratinization and cellular atypia. One of these two subjects was diagnosed as squamous carcinoma of the prostate and transitional cell carcinoma of the bladder. The lesions of 8 female patients were on the trigone and evaluated as normal anatomical variants due to hormonal changes. Three of them were remarkable because of recurrent urinary infections. Apart from the two male patients with squamous cell carcinoma of the prostate the two male patients with current squamous metaplasia have been following up. In this study, we have also reviewed the relationship between squamous metaplasia, infection and malignancy.

Adult↗

PubMed2001

Incidence of squamous neoplasia of the cervix and vagina in women exposed prenatally to diethylstilbestrol (United States).

OBJECTIVES: Women exposed prenatally to diethylstibestrol (DES) have an excess risk of clear-cell adenocarcinoma of the vagina and cervix, but the effect on the incidence of squamous neoplasia is uncertain. The purpose of the current study was to evaluate the long-term risk of developing high-grade squamous neoplasia of the genital tract among women exposed prenatally to DES. METHODS: A cohort comprising 3,899 DES-exposed and 1,374 unexposed daughters was followed for 13 years (1982 1995) for pathology-confirmed diagnoses of high-grade squamous intraepithelial neoplasia (HSIL) of the genital tract. Poisson regression analysis was used to compute relative risks (RR) and 95% confidence intervals (95% CI), adjusting for age, calendar year, and other covariates. RESULTS: The RR (95% CI) among DES-exposed versus unexposed, based on 111 cases of high-grade disease, was 2.1 (1.2-3.8). Adjustment for screening history estimated by the number of years since the last Pap smear had little effect. Risk estimates were higher with earlier intrauterine exposure; the RR (95% CI) for exposure within 7 weeks of the last menstrual period was 2.8 (1.4-5.5). Only two cases of invasive squamous cervical cancer occurred in total, precluding separate analysis. CONCLUSIONS: The findings support an association between in-utero DES exposure and high-grade squamous neoplasia, although a role for more intensive screening among DES-exposed women in the production of this excess could not be completely ruled out.

Carcinoma, Squamous Cell↗

PubMed2003

Small vulvar squamous cell carcinomas and adjacent tissues. A morphologic study.

Vulvar squamous cell carcinomas are of different subtypes and degrees of differentiation, and may be associated with adjacent lichen sclerosus and/or varying degrees of dysplasia. The aim of this investigation was to study small carcinomas with a diameter of less than 2 cm in order to find a possible relation between subtypes of carcinomas and adjacent epithelial changes. Fourteen cases of small vulvar squamous cell carcinomas were totally embedded in paraffin. Serial sectioning made a detailed mapping of all different lesions possible, and a two- and three-dimensional imaging was obtained in each case. Seven patients with keratinizing squamous cell carcinomas (median age 65) had adjacent lichen sclerosus. All carcinomas were completely surrounded by areas of VIN1. VIN2 and VIN3 were not found. Seven patients without lichen sclerosus (median age 58) showed squamous cell carcinomas of the keratinizing type (n=2) or the basaloid type (n=5). Five of these cases were incompletely surrounded by varying degrees of dysplasia, mainly VIN2 and VIN3. Two different pathogenetic pathways for the development of vulvar squamous cell carcinoma are likely.

Adult↗

PubMed2000

Squamous metaplasia of sebaceous gland.

Squamous metaplasia in the skin has been reported in the eccrine ducts as eccrine squamous syringometaplasia (ESS). To our knowledge, squamous metaplasia of sebaceous gland (SMSG) has not been described in human skin. Twenty-two biopsy specimens from patients with pressure lesions after cardiac surgery with extracorporeal circulation were evaluated for the presence of SMSG. Squamous metaplasia of sebaceous gland was identified in five of the eight scalp biopsies and none of the buttock biopsies. The squamous metaplasia began in the germinative outer layer and advanced in a centripetal way. We believe that SMSG is an unspecific change of the sebaceous cells secondary to a chronic injury. Ischemia appears to play a mayor role, but other factors such as chronic trauma or toxicosis can not be ruled out.

Carcinoma, Squamous Cell↗

PubMed2000

Cyclin D1 expression in oral squamous cell carcinomas: clinicopathological relevance and correlation with p53 expression.

The aim of the present study is to study the relationship between cyclin D1 and the clinicopathological features of oral squamous cell carcinomas. The cyclin D1 and p53 expression in oral squamous cell carcinomas from 56 patients (45 men, 11 women) was studied by immunohistochemistry using monoclonal antibodies. The correlation between cyclin D1 and the clinicopathological features of the oral cancers was evaluated. Cyclin D1 expression was found in 63% of oral squamous cell carcinomas; it was often weak but was more frequently positive in high-grade lesions (P=0.019). The expression was positively correlated with p53 expression (P= 0.06). Radiation therapy did not alter the expression of either cyclin D1 or p53 proteins. Expression of these proteins was not related to the age, gender or survival of the patients, or to stages of the tumors. The cyclin D1 expression was more frequently seen in patients with squamous cell carcinomas of oropharynx, palate, floor of mouth and gingiva. To conclude, cyclin D1 was frequently expressed in oral squamous cell carcinomas. This expression was related to the grade of the tumors and was not similar in various regions in the oral cavity, which may indicate the different tumor biology of cancers from these regions.

Adult↗

PubMed2002

Subcellular localization of beta-catenin in malignant cell lines and squamous cell carcinomas of the oral cavity.

BACKGROUND: Beta-catenin, an E-cadherin-associated protein involved in cell-cell adhesion and signaling, has been hypothesized to translocate to the nucleus and activate transcription in several human cancers, including oral squamous cell carcinomas (OSCC). METHODS: In the present study, we analyzed the subcellular localization of beta-catenin in cultures of human oral normal and malignant (cell lines SCC15 and SCC25) keratinocytes and in 24 frozen samples of oral squamous cell carcinomas by a double-staining technique for nucleic acids and beta-catenin. Growth potential, as assessed by cell count at different time periods, was established for normal, SCC15 and SCC25 cell lines; oral squamous cell carcinomas were classified according to the histopathological and malignancy indexes. RESULTS: Beta-catenin localized at the plasma membrane in the normal and SCC15 cells, not in the SCC25 cells, where it localized mostly in the perinuclear and nuclear areas. In the growth assays, SCC25 cell lines proliferated faster than in normal and SCC15 cells over a period of 6 days (cell numbers were significantly different, P < 0.0001). Carcinoma sections showed a combination of membranous, cytoplasmic and, in few invading epithelial islands of two tumors, nuclear localization of beta-catenin. CONCLUSIONS: In oral squamous cell carcinomas, nuclear beta-catenin staining was observed only within invading islands of two carcinomas deep in the underlying connective tissue. On the basis of this study, we conclude that intranuclear beta-catenin does not appear to be a common finding in oral squamous cell carcinomas and that a clear association between intranuclear beta-catenin and histopathological and malignancy indexes in vivo could not be established.

Adolescent↗

PubMed2000

p53, cyclin-D1, PCNA, AgNOR expression in squamous cell cancer of the lip: a multicenter study.

BACKGROUND: The development of squamous cell carcinoma of the lower lip is an interesting model of photocarcinogenesis because of the structural and topographic characteristics of the lips. The purpose of this study was to evaluate the expression of immunohistochemical markers on the lips of patients with lower lip squamous cell carcinoma (LLSCC), compared with a control population. METHODS: Of the 98 subjects involved in the study, 58 were suffering from squamous cell carcinoma of the lower lip. The remaining 40 acted as a control. The case studies were taken from six university and hospital dermatology and plastic surgery departments. Questionnaires were administered to assess the risk factors for LLSCC. The cases involving squamous cell carcinoma underwent surgical excision and punch biopsy specimens were obtained from 20 control patients. Tissues were prepared in 5-microm-thick sections to carry out the following immunohistochemical study: PCNA, p53, AgNOR, cyclin-D1, bcl-2. RESULTS: The lower lip was the predominant location of squamous cell carcinoma, with the following factors playing important roles: chronic sun exposure, history of smoking, alcohol use and familial risk of cutaneous tumors. The male/female ratio in our survey was 5:1. The p53 protein was positive in approximately 50% of SCC cases and in 20% of controls. This protein is mostly associated with chronically photoexposed skin areas. AgNOR positivity increased with the loss of cellular differentiation; a progressive increase in size and a poorly defined shape were evident in poorly differentiated carcinomas. CONCLUSIONS: The results of this multicenter study showed that there is a noticeable difference in the expression of PCNA, p53, cyclin-D1, and AgNOR in tissues from patients with LLSCC and controls.

Aged↗

PubMed1989

Gene amplification and overexpression of EGF receptor in squamous cell carcinomas of the head and neck.

Tumours of the head and neck were examined for gene amplification and expression of the epidermal growth factor (EGF) receptor by Southern blot and Western blot analyses. The EGF receptor gene was found to be amplified in four (19%) of 21 squamous cell carcinomas. The EGF receptor was overexpressed in eight (53%) of 15 squamous cell carcinomas examined, including all four tumours showing gene amplification. No amplification or overexpression of the EGF receptor gene was detected in any of nine malignant or eight benign tumours of other types of the head and neck. The tumours showing amplification and/or overexpression of the EGF receptor gene (8/15) were all identified histologically as well differentiated squamous cell carcinomas, whereas none of the histologically less differentiated squamous cell carcinomas (0/9) showed amplification and/or overexpression of the EGF receptor gene. Within our sample set, no correlation was evident between amplification and/or overexpression and the clinical stage or tumour site. Our results support the possible involvement of gene amplification and overexpression of the EGF receptor in a subclass of squamous cell carcinomas of the head and neck.

Adult↗

PubMed2005

Distinction of pulmonary small cell carcinoma from poorly differentiated squamous cell carcinoma: an immunohistochemical approach.

Accurate morphologic distinction between small cell carcinoma and poorly differentiated squamous cell carcinoma has critical therapeutic significance, but can be limited by crush artifact, tumor necrosis, limited tumor representation, and overlapping morphologic features. We evaluated a panel of antibodies for their efficacy in distinguishing between these neoplasms. Formalin-fixed paraffin-embedded tissue sections of small cell carcinomas and poorly differentiated squamous cell carcinomas underwent immunohistochemical staining with antibodies to thyroid transcription factor-1, p63, high molecular weight keratin, and p16(INK4A). Of 28 small cell carcinomas, 26 (93%) small cell carcinomas showed diffuse moderate or strong staining for thyroid transcription factor-1 with no staining for high molecular weight keratin and p63. In contrast, 27/28 (96%) poorly differentiated squamous cell carcinomas manifested opposite immunoreactivities, with diffuse moderate or strong staining for high molecular weight keratin and p63, and no or minimal staining for thyroid transcription factor-1. In two additional cases originally interpreted as small cell carcinoma, high molecular weight keratin highlighted small numbers of neoplastic large cells, leading to reclassification as combined small cell and non-small cell carcinomas. p16(INK4A) expression varied widely in poorly differentiated squamous cell carcinomas, but was consistently moderate or strong and diffuse in small cell carcinomas, and proved helpful in the two thyroid transcription factor-1-negative small cell carcinomas. This study demonstrates that a panel consisting of antibodies to thyroid transcription factor-1, p63, high molecular weight keratin, and p16(INK4A) is highly effective for distinguishing between small cell carcinoma and poorly differentiated squamous cell carcinoma. This panel also facilitates diagnosis of combined small cell and non-small cell carcinomas.

Carcinoma, Small Cell↗

PubMed2005

Nuclear galectin-3 expression is an independent predictive factor of recurrence for adenocarcinoma and squamous cell carcinoma of the lung.

The tumor stage is the most powerful prognostic tool for predicting the survival rates of lung carcinoma patients. However, prognosis of individual patients is difficult in part because of the marked clinical heterogeneity among such patients. Galectins are involved in cell growth, apoptosis and cell migration features, and their diagnostic and prognostic values have already been demonstrated in various types of cancers. In the present paper we analyze the potential prognostic value of immunohistochemical galectin-3 expression in lung adenocarcinomas and squamous cell carcinomas. In all, 165 squamous cell carcinomas and 121 adenocarcinomas were immunostained for galectin-3. In each case the immunohistochemical analyses consisted of an evaluation of the percentage of tumor cells stained and the intensity of staining. An IP score (ie Intensity x Percentage) was thus determined for each lung carcinoma. A large majority of cases displayed galectin-3 expression. While the cytoplasmic staining in the squamous cell carcinomas was focal and moderately intense, the staining in the adenocarcinomas was diffuse and intense. The IP scores were significantly (P=0.0001) higher in the adenocarcinomas than in the squamous cell carcinomas. The difference in nuclear expression profiles between the two cancer types was statistically significant (P=0.0005). Cox multivariate analysis carried out on the patients' genders, the TNM classification and the galectin-3-related variables showed that of the galectin-3-related variables, only the nuclear location of galectin-3 was identified as a prognostic indicator of recurrence independent of the clinicopathological features characterizing the patients (P=0.02). The prognostic contribution of this latter variable was enhanced when the patients with relapse-free follow-ups longer than 8 months were considered (P=0.005). Galectin-3 immunohistochemical expression differs between squamous cell carcinomas and adenocarcinomas, but the nuclear expression of galectin-3 behaves as a significant prognostic predictor for all the cases as a group.

Adenocarcinoma↗

PubMed2006

Squamous cell carcinoma: from precursor lesions to high-risk variants.

Cutaneous squamous cell carcinoma is second only to basal cell carcinoma in its incidence within our population. It is among the most common types of neoplasm afflicting the human race. Most cases are related to exposure to sunlight. This initial portion of the chapter will focus upon the biologic progression that results in the ultimate development of fully formed squamous cell carcinoma. The latter portion will focus upon the histologic features of squamous cell carcinoma, which may be potential prognostic indicators. While pathologists currently provide clinicians with information about many histologic features that may affect the outcome for patients with melanoma, there is little impetus for similar behavior on the part of pathologists when diagnosing squamous cell carcinomas. This is largely due to the relatively low metastasis rate for these tumors compared with melanomas; however, it may be possible for pathologists to separate out those squamous cell carcinomas with a higher chance for recurrence and metastasis. This chapter will examine many of these histologic features and propose a rationale for including this information in pathology reports.

Carcinoma, Squamous Cell↗

PubMed2006

The diagnostic utility of immunohistochemistry in distinguishing between epithelioid mesotheliomas and squamous carcinomas of the lung: a comparative study.

As both mesotheliomas and squamous carcinomas can present a wide variety of morphological patterns, they can on occasion be confused. Recently, some groups of investigators have called attention to the difficulties that sometimes exist in distinguishing between these malignancies and the need to define a panel of markers that can assist in reaching the correct diagnosis. The aim of the present study is to compare the value of the various immunohistochemical markers currently available for the diagnosis of mesothelioma and squamous carcinoma of the lung. A total of 30 epithelioid pleural mesotheliomas exhibiting a solid or predominantly solid pattern, and 30 nonkeratinizing squamous carcinomas of the lung were investigated for the expression of the following markers: podoplanin, calretinin, mesothelin, WT1, keratin 5/6, keratin 7, p63, carcinoembryonic antigen (CEA), MOC-31, Ber-EP4, B72.3, BG-8 (Lewis(y)), leu-M1 (CD15), and thyroid transcription factor-1 (TTF-1). All 30 (100%) of the mesotheliomas reacted for calretinin, mesothelin and keratin 7, 93% each for podoplanin, WT1 and keratin 5/6, 13% for Ber-EP4, 7% each for p63, MOC-31 and BG-8, and 0% for B72.3, CEA, leu-M1 and TTF-1. All 30 (100%) of the squamous carcinomas were positive for p63 and keratin 5/6, 97% for MOC-31, 87% for Ber-EP4, 80% for BG-8, 77% for CEA, 57% for keratin 7, 40% for calretinin and B72.3, 30% for leu-M1, 27% for mesothelin, 15% for podoplanin, and 0% for WT 1 and TTF-1. After analyzing the results, it is concluded that from a practical point-of-view, a combination of two positive mesothelioma markers (WT1 and calretinin or mesothelin) with two negative mesothelioma markers (p63 and MOC-31) would allow the differential diagnosis to be established between epithelioid mesotheliomas and squamous carcinomas of the lung in nearly all instances.

Biomarkers, Tumor↗

PubMed2006

Detection of EGFR- and HER2-activating mutations in squamous cell carcinoma involving the head and neck.

Recent reports have indicated that mutations in the epidermal growth factor receptor-1 (EGFR) occur in about 7% of patients with squamous cell carcinoma of the head and neck. It is known that many patients with non-small-cell lung cancer who respond to the EGFR inhibitors gefitinib and erlotinib have tumors with EGFR-activating mutations. This might suggest that patients with head and neck squamous carcinoma, who also have tumors with EGFR-activating mutations, might represent a patient population who could benefit from gefitinib or erlotinib therapy. High-resolution melting amplicon analysis (HRMAA) is a recently described technique which can be used for screening tumor DNA isolated from paraffin blocks for tyrosine kinase-activating mutations. In this report we screened 24 cases of squamous cell carcinoma, either primary in the head and neck or secondarily involving the head and neck area, for activating mutations in EGFR exons 18, 19, 20, 21, and for HER2 exons 19 and 20. All cases were followed up by direct DNA sequencing. Two (8%) of the 24 cases were positive. One case was a maxillary sinus tumor which contained an exon 20-activating mutation (N771YinsG). Surprisingly, the other case was a primary squamous cell carcinoma of the skin which invaded the head and neck area only secondarily. This tumor contained an exon 19-activating mutation (G729E). No HER2-activating mutations were found. The presence of a small number of squamous cell carcinomas in the head and neck area with EGFR-activating mutations suggests the existence of a population of patients who could derive benefit from gefitinib or erlotinib therapy. HRMAA could serve as a screening method to easily and rapidly identify these patients.

Adult↗

PubMed2002

Reduced apoptotic levels in squamous but not basal cell carcinomas correlates with detection of cutaneous human papillomavirus.

We have investigated the apoptotic levels and expression of the apoptotic inducer Bak in non-melanoma skin cancers. Squamous cell carcinomas of known human papillomavirus status from immunocompetent patients were analysed for the expression of the Bak protein, and the expression profile was compared both to the presence of apoptotic cells and the proliferation marker Ki-67. We demonstrate an inverse correlation between human papillomavirus positivity and Bak expression in squamous cell carcinomas, with concomitantly fewer apoptoic cells being detected in the human papillomavirus positive tumours. Bak expression was not observed in basal cell carcinomas irrespective of human papillomavirus status, suggesting that Bak only plays a role in signalling apoptosis in squamous, but not basal, cell cancers. No differences were observed in the proliferation rates between papillomavirus positive and negative squamous cell tumours. However, a significant decrease in the number of apoptotic cells was observed in human papillomavirus-positive squamous cell carcinomas which suggests that the virus may have significantly altered the relationship between proliferation and apoptosis in a proportion of these tumours.

Apoptosis↗

PubMed2003

Prognostic value of nuclear survivin expression in oesophageal squamous cell carcinoma.

Survivin, a new member of the family of apoptosis inhibitors, is expressed almost exclusively in proliferating cells, above all in cancers. Subcellular localisation and prognostic implications of the survivin protein have not yet been determined in oesophageal squamous cell carcinoma. The survival of 84 patients with oesophageal squamous cell carcinomas was correlated with the extent of immunohistochemical survivin expression in tumour cell nuclei. Tumours were scored positive when >5% cells stained positive. Patients were followed up for at least 5 years or until death. In normal oesophageal squamous cell epithelium, some cytoplasmic survivin expression was detected in the basal cells, whereas proliferating cells showed nuclear staining of survivin. Nuclear expression of survivin was also detected in 67 cancers (80%). The mean survival for patients of this group (28 months, range 20-36) was significantly less than that for patients without survivin expression in the tumour cell nuclei (108 months, range 62-154, P=0.003). Using univariate analysis, nuclear survivin expression (P=0.003), tumour depth (P=0.001), lymph node metastasis (P=0.003) and stage (P<0.001) were the best predictors of survival. In contrast, cytoplasmic survivin staining was noted in 53 (63%) tumours and had no prognostic relevance. In conclusion, the analysis of nuclear survivin expression identifies subgroups in oesophageal squamous cell cancer with favourable (survivin(-)) or with poor prognosis (survivin(+)). We suggest that the determination of nuclear survivin expression could be used to individualise therapeutic strategies in oesophageal squamous cell cancer in the future.

Adult↗