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Human telomerase reverse transcriptase expression and its clinical significance in laryngeal squamous cell carcinoma.

CONCLUSIONS: Upregulation of hTERT mRNA plays an important role during the occurrence and development of laryngeal squamous cell carcinoma. Most hTERT mRNA in plasma from patients with laryngeal squamous cell carcinoma is derived from tumour cells; moreover, the determination of plasma hTERT mRNA contributes to tumour diagnosis and the observation of curative effect. OBJECTIVES: To establish a real-time fluorescent reverse transcriptase polymerase chain reaction (RT-PCR) and to quantitate the level of human telomerase reverse transcriptase (hTERT) mRNA in carcinoma tissue and plasma from patients with laryngeal squamous cell carcinoma. We also wished to evaluate the role that hTERT mRNA expression plays during the occurrence and development of laryngeal squamous cell carcinoma, to probe the correlation between the expression level and the clinical and pathological parameters and to investigate the value of the determination of plasma hTERT mRNA in tumour diagnosis and the observation of curative effect. MATERIAL AND METHODS: A real-time fluorescent RT-PCR and a Lightcycler PCR system were used to quantitate the expression level of hTERT mRNA. RESULTS: The expression levels of hTERT mRNA (NhTERT) from laryngeal squamous cell carcinoma tissue and corresponding adjacent non-cancerous tissue were 62.6 +/- 21.7 and 3.5 +/- 1.9, respectively. NhTERT was significantly elevated in laryngeal squamous cell carcinoma tissue, rising to 17.9-fold on average, but there was no significant correlation between NhTERT and either tumour location, differentiation degree, T grade or N grade. For healthy examinees, NhTERT in plasma was 1.3 +/- 0.9, compared to 13.1 +/- 9.4 and 9.3 +/- 5.8 in patients with laryngeal squamous cell carcinoma examined before and 2 days after surgery, respectively. Compared to healthy examinees, NhTERT in plasma from patients with laryngeal squamous cell carcinoma was significantly elevated; moreover, 2 days after surgery, NhTERT in plasma had decreased significantly in these patients.

Adult↗

Polymorphisms of death pathway genes FAS and FASL in esophageal squamous-cell carcinoma.

BACKGROUND: The FAS receptor-ligand system is a key regulator of apoptotic cell death, and loss of FAS expression and gain of FAS ligand (FASL) expression play important roles in the development and progression of cancer. Single-nucleotide polymorphisms in the promoter region of the FAS (G or A at position -1377 [FAS -1377G/A] and A or G at position -670 [FAS -670A/G]) and FASL (T or C at position -844 [FASL -844T/C]) genes alter the transcriptional activity of these genes. We examined the association between these polymorphisms and risk of the development and metastasis of esophageal squamous-cell carcinoma. METHODS: Genotypes of 588 case patients with esophageal squamous-cell carcinoma and 648 control subjects were determined by polymerase chain reaction-based restriction fragment length polymorphism. Associations with the risk of esophageal squamous-cell carcinoma were estimated by logistic regression. All statistical tests were two-sided. RESULTS: We observed a statistically significantly increased risk of esophageal squamous-cell carcinoma associated with the FAS -1377AA (odds ratio [OR] = 1.79, 95% confidence interval [CI] = 1.29 to 2.48; P<.001) or FAS -670GG (OR = 1.72, 95% CI = 1.26 to 2.34; P<.001) genotype, which are in strong linkage disequilibrium compared with the FAS -1377GA or GG or the FAS -670AG or AA genotype, respectively. An increased risk of esophageal squamous-cell carcinoma was also associated with the FASL -844CC genotype (OR = 2.06, 95% CI = 1.64 to 2.59; P<.001) compared with the FASL -844CT or TT genotype. Gene-gene interactions of FAS and FASL polymorphisms increased the risk of esophageal squamous-cell carcinoma in a multiplicative manner (OR for the presence of both FAS -1377AA and FASL -844CC genotypes = 4.55, 95% CI = 2.75 to 7.48; P =.001, test for homogeneity). Statistically significant interactions were found between these polymorphisms in FAS and FASL and tobacco smoking. None of the polymorphisms was associated with risk of differentiation or metastasis of esophageal squamous-cell carcinoma at diagnosis. CONCLUSION: Genetic polymorphisms in the death pathway genes FAS and FASL appear to be associated with an increased risk of developing esophageal squamous-cell carcinoma.

Adaptor Proteins, Signal Transducing↗

Squamous mucosal alterations in esophagectomy specimens from patients with end-stage achalasia.

Achalasia is an esophageal motor disorder in which the primary morphologic changes are found in the myenteric plexus. However, a number of secondary alterations are characteristically found in esophagectomy specimens, including the mucosa. In addition, these patients are at increased risk of developing esophageal squamous cell carcinoma. We studied the squamous mucosal alterations in 35 esophagectomy specimens from patients with end-stage achalasia and compared them with those found in the squamous mucosa near the esophagogastric junction from pediatric autopsies (</=18 years) from patients with no known esophageal disease. A representative block was immunostained for p53 (DO7), CD3, and CD20. p53 immunoreactivity was graded as follows: 0 = no staining; 1+ = rare basal cell staining; 2+ = extensive basal cell staining; 3+ = suprabasilar staining. Intraepithelial lymphocyte counts were performed by counting five high power fields (HPF) and calculating an average/HPF. Ages of achalasia patients at esophagectomy ranged from 21 to 78 years (mean 56 years), including 20 men and 15 women. Disease duration ranged from 1 to 44 years (mean 17 years). In all cases the squamous mucosa from achalasia patients was markedly hyperplastic with papillomatosis and basal cell hyperplasia. p53 staining in the squamous mucosa from achalasia patients was significantly more common than in controls (32 of 35 [91%] vs 1 of 17 [6%]; p <0.05). In all achalasia cases CD3+ cells far outnumbered CD20+ cells. There was a significantly greater number of CD3+ cells in achalasia cases (range 32-239/HPF; mean 107/HPF) compared with controls (range 0.8-12/HPF; mean 6/HPF) (p <0.05). In conclusion, the squamous mucosa in esophagectomy specimens from patients with end-stage achalasia shows significant alterations including marked squamous hyperplasia, an increased frequency of p53 immunoreactivity, and increased numbers of CD3+ cells when compared with controls. These changes may be related to the increased risk of squamous cell carcinoma in these patients.

Adolescent↗

Immunohistochemical detection of metallothionein and MIB1 in uterine cervical squamous lesions.

Metallothioneins (MTs) are ubiquitous low molecular weight proteins with a high affinity for heavy metal ions such as zinc, copper, cadmium, and platinum. Immunohistochemically detectable MT overexpression has been demonstrated in a variety of cancers, especially breast carcinoma. In this study, the immunohistochemical expression of MT in normal cervical squamous epithelia, cervical intraepithelial neoplasms (CINs), and invasive cervical squamous carcinomas was investigated. Immunohistochemical staining for proliferating cells using the MIB1 antibody was also performed. In normal squamous epithelia (n = 31), positive staining with MT was confined to basal and parabasal cells. In cases of koilocytosis (n = 14) and CIN I (n = 10), staining was also largely confined to basal and parabasal cells, with only occasional cases of CIN I exhibiting positivity within higher cell layers. Cases of CIN II (n = 14) showed positive staining largely confined to basal and parabasal cells, with staining of higher cell layers in a few cases. In the majority of cases of CIN III (n = 29), there was diffuse positive staining throughout the full epithelial thickness and, in almost all cases, positive staining was present above the basal and parabasal layers. Positive staining was present in 19 of 21 invasive squamous carcinomas. With MIB 1, positivity was confined to the parabasal layer in normal squamous epithelia. In cases of CIN, positive cells were present in progressively higher cell layers, in accordance with the grade of CIN. There was widespread positive staining in all cases of invasive squamous carcinoma. Overexpression of MT, demonstrated immunohistochemically, is associated with CIN III and invasive cervical squamous carcinoma, lesions which exhibit the highest proliferative activity, as shown by MIB1 immunostaining. MT overexpression in cervical squamous lesions appears to occur at some point along the spectrum of high grade CIN and may be related to cell proliferation.

Antigens, Nuclear↗

Squamous cell carcinoma of the prostate.

Eleven case of squamous cell carcinoma of the prostate have been divided into four groups according to their histological features and natural history: a pure squamous cell carcinoma of the prostate (one case); b common prostatic adenocarcinoma with malignant squamous component after oestrogen treatment (two); c urothelial carcinoma of the prostate with malignant squamous cell metaplasia (four); and d urothelial carcinoma of the urinary bladder with squamous cell metaplasia growing into the prostate (four). The squamous portions may spread to invade the fibromuscular stroma and grow in prostatic ducts. Necrosis of comedo type and inflammatory infiltrates appeared in a number of cases. The survival times of nine patients ranged from 1 to 17 months. Squamous components were shown by immunohistochemistry to contain various keratin types, carcino-embryonic antigen and peanut agglutinin binding sites. Whenever a squamous cell carcinoma in the prostate is diagnosed histologically various possibilities as to its origin should be considered.

Aged↗

nm23-H1 protein immunoreactivity in intraepithelial neoplasia and invasive squamous cell carcinoma of the uterine cervix.

Differences in the immunohistochemical expression of the 17 kDa protein encoded by the human nm23-H1 gene were studied in premalignant lesions and invasive squamous cell carcinoma (SCC) (N = 8) of the cervix using routine streptavidin-biotin immunohistochemistry and a polyclonal antibody to the nm23-H1 protein. The premalignant lesions were koilocytic atypia due to wart virus infection (N = 5), low-grade cervical intraepithelial neoplasia (CIN) (N = 7) and high-grade CIN (N = 7). The carcinomas were either moderately (N = 3) or poorly differentiated (N = 5). The non-neoplastic controls were normal squamous epithelium from cases with uterine prolapse (N = 7) and normal squamous epithelium not affected by the infective or neoplastic areas of some of the cases with wart virus infection (N = 2) and carcinoma (N = 2). Moderate to strong cytoplasmic and, occasionally, nuclear immunostaining for the nm23-H1 protein was seen in all cells above the basal layer of the normal squamous epithelium. However, most of the cervical SCC show a relative reduction in nm23-H1 immunoreactivity (7/8 cases; 88%). This difference in nm23-H1 expression was statistically significant (P = 0.0006; Chi-squared test with continuity correction). All of the cases with wart virus infection (N = 5; 100%) displayed moderately strong nm23-H1 immunostaining throughout the squamous epithelium except for the basal layer where no staining was observed. The cases that had low-grade squamous dysplasia of the cervix (CIN I-II) (N = 7; 100%) also displayed moderate to strong nm23-H1 immunoreactivity in the epithelium except for the basal layer (CIN I) or the lower two-thirds of the epithelium (CIN II). nm23-H1 Immunoreactivity was either absent or was significantly reduced in all of the high-grade CIN (CIN III) cases (N = 7; 100%) in which only the non-dysplastic superficial third of the squamous epithelium displayed nm23-H1 immunolabeling. The difference in nm23-H1 expression between low-grade and high-grade CIN cases was statistically significant (P = 0.0013; Chi-squared test with continuity correction). Similarly, the difference between low-grade CIN and SCC cases in the expression of nm23-H1 was also significant (P = 0.0041; Chi-squared test with continuity correction). However, no statistically significant difference in nm23-H1 immunoreactivity was found between cases of high-grade CIN and SCC. In conclusion, nm23-H1 protein immunoreactivity is reduced in high-grade CIN and cervical SCC but not in low-grade CIN. These findings suggest that reduced expression of the protein may be important early in the sequential development of cervical squamous neoplasia.

Antigens, Neoplasm↗

A rapid serological detection method for squamous cell carcinoma.

OBJECTIVE: We conjugated the squamous cell carcinoma (CA)-associated antibody (anti-YM antibody) with gelatin particles. We found that these particles reacted specifically with the tumor-associated antigen (YM antigen) in serum samples from patients with squamous cell CA of the uterine cervix and various organs (GPA reaction). METHODS: 1) We performed immunohistochemical studies of the YM antigen in dysplasia and invasive squamous cell CA of the uterine cervix; 2) We measured the GPA reaction in various malignant and non-malignant gynecologic diseases. RESULTS: 1) Immunohistochemical localization of the YM antigen was over 75% in cases of dysplasia and invasive squamous cell CA of the uterine cervix, and was 21% in normal squamous epithelium of the uterine cervix. 2) The GPA reaction in gynecologic diseases was positive in 57.1% of the dysplasia cases; in CIS cases, 69.2%; in cervical CA, 83.0%; in corpus CA, 25.0%; in leiomyoma 16.7%; and in pregnant serum samples, 66.7%, 3) GPA reactions in non-ob-gyn cases were positive in 68.8% of the cases of squamous cell CA of the head and neck; 66.7% in cases of squamous cell CA of the lung; and 25.0% in adenoCA of the lungs whereas the sera of patients with benign tumors and of healthy persons were free of the YM antigen. CONCLUSION: We concluded that this newly developed GPA-reaction measurement is a simple and reliable serologic test for detecting the initial stage of squamous cell CA of various organs and for monitoring its postoperative status.

Agglutination Tests↗

Intraepithelial elastic fibers and intracytoplasmic glycogen: diagnostic aids in differentiating keratoacanthoma from squamous cell carcinoma.

A significant statistical difference was found between the incidence of intraepithelial elastic fibers in keratoacanthoma and squamous cell carcinoma arising in actinic keratosis (P < 0.001). There was no significant difference when keratoacanthoma was compared to adenoid squamous cell carcinoma (P = 0.13) and de novo squamous cell carcinoma (P = 0.73). However, in keratoacanthoma intraepithelial elastic fibers were found in areas of pseudoepitheliomatous hyperplasia and in the central keratin plug, as well as in areas of infiltrating, peripheral keratinocytes. In adenoid squamous cell carcinoma and de novo squamous cell carcinoma, the intraepithelial elastic fibers were found only in areas of atypical epithelial cells at the margin of the neoplasm. Intracytoplasmic glycogen was found to be statistically more abundant in keratoacanthoma than in squamous cell carcinoma arising in actinic keratosis (P < 0.001), adenoid squamous cell carcinoma (P < 0.001), and in de novo squamous cell carcinoma (P < 0.001)

Carcinoma, Squamous Cell↗

Morules in endometrial carcinoma and benign endometrial lesions differ from squamous differentiation tissue and are not infected with human papillomavirus.

BACKGROUND: Squamous differentiation/squamous metaplasia is often associated with endometrial adenocarcinoma and benign lesions, such as endometrial hyperplasia and chronic endometritis. Morules have distinct histological characteristics, and are referred to as squamous metaplasia or squamoid metaplasia. AIM: To focus on the histological characteristics of morules and clarify the difference between morules and squamous differentiation. MATERIALS/METHODS: Twenty endometrioid carcinomas with morules or squamous differentiation, five adenosquamous carcinomas, and eight non-carcinomatous endometrial lesions with morules were investigated. Numerous antibodies for epithelial membrane antigen (EMA), involucrin, cytokeratins, neuropeptides, and oncofetal antigens were used for immunohistochemistry. In situ hybridisation and polymerase chain reaction were used to detect human papillomavirus (HPV). RESULTS: The morules observed were uniform cell clusters, with no squamous differentiation. They were immunonegative for epithelial antigens including involucrin, EMA, and cytokeratins, but were positive for neurone specific enolase. A few morules were immunopositive for acetylcholine esterase, and one case was positive for somatostatin; neither oncofetal nor proliferative cell markers, including blood group A, B, and AB, or other neuropeptides were demonstrated in the morules. HPV DNA was not found in either the morules in the carcinomas or in the benign lesions. However, true squamous differentiation tissue in four endometrioid carcinomas and two adenosquamous carcinomas was HPV positive using in situ hybridisation. CONCLUSION: Morules are histologically distinct from squamous metaplasia/squamous differentiation tissue. Morules are thought to be neuroectodermal-like cell clusters, and are not infected with HPV. In contrast, some of the true squamous differentiation tissue was associated with HPV infection.

Adenocarcinoma↗

Comprehensive characterization of annexin I alterations in esophageal squamous cell carcinoma.

PURPOSE: The purpose is to characterize alterations of the annexin I gene, its mRNA, and protein expression in esophageal squamous cell carcinoma. EXPERIMENTAL DESIGN: Fifty-six cases of esophageal squamous cell carcinoma were analyzed using four microsatellite markers flanking the annexin I gene (9q11-q21) to identify loss of heterozygosity. In addition, we performed (a) single-strand conformation polymorphism and DNA sequencing along the entire promoter sequence and coding region to identify mutations, (b) real-time quantitative reverse transcription-PCR of RNA from frozen esophageal squamous cell carcinoma tissue (n = 37) and in situ hybridization (n = 5) on selected cases to assess mRNA expression, and (c) immunohistochemistry (n = 44) to evaluate protein expression. The prevalence of the allelic variants identified in the first 56 patients was refined in 80 additional esophageal squamous cell carcinoma patients and 232 healthy individuals. RESULTS: Forty-six of 56 (82%) esophageal squamous cell carcinoma patients showed loss of an allele at one or more of the four microsatellite markers; however, only one (silent) mutation was seen. Two intragenic variants were identified with high frequency of allelic loss (A58G, 64%; L109L, 69%). Thirty of 37 (81%) esophageal squamous cell carcinoma patients showed reduced annexin I mRNA expression, which was confirmed by in situ hybridization, whereas annexin I protein expression was reduced in 79% of poorly differentiated tumor cell foci but in only 5% of well-differentiated tumor foci, although allelic loss on chromosome 9 was found in both tumor grades. CONCLUSIONS: Allelic loss of annexin I occurs frequently, whereas somatic mutations are rare, suggesting that annexin I is not inactivated in esophageal squamous cell carcinoma via a two-hit mechanism. A decrease in annexin I protein expression was confirmed, consistent with a quantitative decrease in mRNA expression, and appeared to be related to tumor cell differentiation. We conclude that annexin I is not the tumor suppressor gene corresponding to the high levels of loss of heterozygosity observed on chromosome 9 in esophageal squamous cell carcinoma; however, dysregulation of mRNA and protein levels is associated with this tumor type.

Alleles↗

Atypical squamous cells as a diagnostic pitfall in pulmonary Wegener's granulomatosis. A case report.

BACKGROUND: Wegener's granulomatosis (WG) is characterized by systemic, necrotizing, granulomatous inflammation accompanied by vasculitis. It classically involves the triad of the upper respiratory tract, lungs and kidneys. Isolated pulmonary lesions of WG may present in some patients as pulmonary masses, simulating neoplasms. The features of WG can be suggested by cytologic study. Atypical epithelial cells associated with WG have previously been reported as a cause of a false positive diagnosis of bronchoalveolar carcinoma. CASE: In this case the cytologic findings included atypical squamous cells in a background of acute, chronic and granulomatous inflammation. In several respiratory specimens the atypical squamous cells were incorrectly interpreted as diagnostic of squamous cell carcinoma. The correct diagnosis of WG was confirmed with open lung biopsy, which demonstrated necrotizing granulomatous inflammation with geographic necrosis and associated vasculitis. CONCLUSION: Markedly atypical squamous cells mimicking squamous cell carcinoma can be found accompanying the inflammatory process associated with WG and are a possible diagnostic pitfall. The possibility of WG as well as other inflammatory processes should always be considered in the differential diagnosis of squamous cell carcinoma of the lung. This case is the only reported case of WG in which atypical squamous cells were a diagnostic pitfall, initially suggesting a diagnosis of squamous cell carcinoma.

Adult↗

P53 in squamous metaplasia: a marker for risk of respiratory tract carcinoma.

Dysplasia in squamous metaplasia of the respiratory tract was believed to be a reversible premalignant lesion. Recently, presumably irreversible genetic alterations have been demonstrated in squamous metaplasia with dysplasia in lung-resection specimens. The genetic alterations were closely similar to those in adjacent bronchial carcinoma. There remains the question of which changes in squamous metaplastic lesions are premalignant, and which of these changes predict the occurrence of carcinoma of the respiratory tract. The purpose of this study was to determine the positive predictive value for respiratory-tract malignancy of the grade of dysplasia, p53 immunoreactivity, proliferative activity, and Bcl-2 in bronchial biopsy specimens exhibiting squamous metaplasia. Bronchial biopsies of 51 patients with squamous metaplasia diagnosed between 1982 and 1993 were used. Immunohistochemistry was done after microwave pretreatment of the biopsy specimens. Only unequivocally stained nuclei were counted. Normal bronchial epithelium obtained from autopsies was used as a control. In 31 patients, a synchronous or metachronous carcinoma was present (61%). Positive p53 immunoreactivity was found in 22 of the 51 patients (43%). The positive predictive values of p53 and of a high grade of dysplasia for carcinoma of the respiratory tract were 91% and 80%, respectively. Although the hyperproliferative state of squamous metaplastic lesions was clearly established, neither the percentage of MIB-1 labelling nor the mitotic index distinguished patient groups with and without carcinoma. No increased Bcl-2 immunostaining was found in squamous metaplasia. In conclusion, p53 immunoreactivity in squamous metaplastic lesions in bronchial biopsies is a marker of carcinoma of the respiratory tract.

Adenocarcinoma↗

Lectin histochemistry on squamous metaplasia in different epithelial tumors of dogs.

Biotinylated lectins and avidin-biotin-peroxidase complex were used to study the correlation between cellular glycoconjugates' expression and squamous maturation in normal canine skin and in various epithelial neoplasms. Normal skin tissue was obtained from five, male, random-source dogs, 5 to 7 years old. The tumors tested, selected from the files of our Department, were fifteen squamous cell carcinomas from different tissue origin, five hepatoid perianal gland adenocarcinomas with squamous metaplasia, and fourteen solid mammary carcinomas with and without histologic evidence of squamous metaplasia. Except for mammary gland carcinomas, all tumors had been surgically excised from male dogs. Intermediate filament aggregation of twelve solid mammary gland carcinomas were studied electron microscopically. The basal and the lower spinous cells in normal skin and the less differentiated cells in squamous cell carcinomas stained moderately with Griffonia simplicifolia agglutinin-I. Spinous and granular cell layers stained strongly with Phytolacca americana mitogen and Arachis hypogaea agglutinin. Both lectins stained well-differentiated cells in squamous cell carcinomas. The electron microscopic study carried out in solid carcinomas of mammary glands revealed some relationship between the presence of intracytoplasmic tonofibrils and the binding of Griffonia simplicifolia agglutinin-I and Phytolacca americana mitogen to the tumors tested. Our results suggest that the glycosylation pattern occurring during normal keratinocyte differentiation is conserved in squamous cell carcinomas and that Griffonia simplicifolia agglutinin-I and Phytolacca americana mitogen may represent useful tools in distinguishing poorly differentiated squamous cell carcinomas from other poorly differentiated mammary epithelial tumors.

Adenocarcinoma↗

Human papillomavirus in sinonasal papillomas and squamous cell carcinoma.

The diagnostic and prognostic relevance of human papillomavirus (HPV) types 6, 11, 16, and 18 in squamous papilloma, inverted papilloma, and squamous carcinoma of the sinonasal epithelium was examined using the polymerase chain reaction (PCR) technique. Four (15%) of 26 squamous papillomas, 7 (24%) of 29 inverted papillomas, and 1 (4%) of 24 squamous carcinomas were positive for HPV when examined using the PCR amplification technique. Human papillomavirus 6 was present in 5 specimens (3 squamous and 2 inverted papillomas); HPV-11 was present in 6 specimens (1 squamous and 5 inverted papillomas); and HPV-18 was present in 1 of 24 squamous carcinomas. HPV-16 was not identified in any specimen. The proportion of tissue samples showing HPV presence, and the association of HPV types 6 and 11 with benign lesions and HPV-18 with malignant lesions, are both in accord with findings from prior investigations. Two major questions regarding nasal papilloma are the probability for lesion recurrence after surgical excision and the risk for malignant transformation. There is no unanimity of opinion regarding the prognostic value of histopathologic dysplasia to forecast these outcomes. HPV is etiologically related to a subset of sinonasal papillomas and squamous carcinoma, and those with benign and malignant clinical course are separable on basis of HPV type. Because of the paucity of these nasal lesions, a multi-institutional prospective collaborative study is the ideal way to address these questions.

Carcinoma, Squamous Cell↗

Immunohistochemical analysis of cyclin A, cyclin D1 and P53 in mammary tumors, squamous cell carcinomas and basal cell tumors of dogs and cats.

The involvement of cyclin A, cyclin D1 and p53 proteins in canine and feline tumorigenesis was analyzed immunohistochemically. In the present study, a total of 176 cases were examined, among which there were 108 canine cases (75 mammary lesions, 16 squamous cell carcinomas and 17 basal cell tumors) and 68 feline cases (43 mammary lesions, 20 squamous cell carcinomas and 5 basal cell tumors). Speckled nuclear staining for cyclin A was observed in 19/38 (50%) canine malignant mammary tumors and 18/37 (48.6%) feline mammary carcinomas, while this was not seen in benign mammary tumors of either dogs or cats. Marked intense nuclear cyclin A staining was seen in 7/16 (43.8%) canine squamous cell carcinomas and 18/20 (90.0%) feline squamous cell carcinomas. Only 3/17 (17.6%) canine basal cell tumors showed slight and scattered staining for cyclin A. Expression of cyclin D1 was very rare in both canine and feline tumors. Nuclear staining of p53 was found in 7/37 (18.9%) feline mammary carcinomas. Intense immunoreactivity for p53 was found in 6/16 (37.5%) canine squamous cell carcinomas and 8/20 (40%) feline squamous cell carcinomas. These results suggest that cyclin A may have a role in the proliferation of canine malignant mammary tumors, feline mammary carcinomas and squamous cell carcinomas of dogs and cats, and p53 may associate with the tumorigenesis of feline mammary carcinomas and squamous cell carcinomas of dogs and cats.

Animals↗

Oncogene expressions detected by in situ hybridization of squamous metaplasia, dysplasia and primary lung cancer in human.

In order to elucidate the dynamic changes of oncogene expression in the sequential cascade of squamous metaplasia, dysplasia, and squamous cell carcinoma of the bronchial epithelium, hybridization in situ was employed with a biotinylated oncogene probe. The expression of c-myc was localized exclusively in nuclei. While normal bronchial epithelium revealed no discernible clumps of c-myc grains, except occasional grains less than 3 per cell, squamous metaplasia showed increased number of grains and a few clusters of c-myc grains. In dysplasia, c-myc expression was more intensive than in squamous metaplasia. Approximately, 1/3 to 2/3 of tumor cell populations of squamous cell carcinomas of the lung revealed tremendously increased c-myc expression. In addition clumpy grains of c-myc in squamous cell carcinoma appeared more frequently than in squamous metaplasia or dysplasia. The c-myc expression was found to vary between different samples and within each cancer, and not all cancer cells expressed c-myc. These data indicate that c-myc oncogene plays it's role on reprogramming for growth control of cell populations particularly in multistage carcinogenesis and progression of lung cancer. These dynamic alterations of c-myc expression suggest that neoplastic transformation may occur conceivably at the dysplastic phase eventually resulting in carcinoma in situ. This means, in turn, squamous dysplasia is a putative precancerous lesion of the human lung.

Bronchial Neoplasms↗

Papillary squamous cell carcinoma of the cervix in Uganda: a report of 20 cases.

BACKGROUND: Non-glandular papillary carcinoma of the cervix are uncommon tumours. In Uganda where cervical carcinoma is very common, no cases of papillary squamous cell carcinoma of the cervix has been reported. OBJECTIVES: To ascertain the occurrence and describe the clinicopathological features of papillary squamous cell carcinoma of the cervix in Uganda. STUDY DESIGN: Retrospective review of histologically diagnosed cases of squamous cell carcinoma of cervix with papillary structures. METHODS: Retrospective review of cases of cervical carcinoma diagnosed in the Pathology Department, Makerere University from 1968 to 1973 was done. Cases with features of squamous differentiation and forming papillary pattern were then selected. RESULTS: Twenty cases were encountered and the ages of the patients ranged from 22 to 70 years (mean 46.6 years). Histologically, the tumours had thin to broad fibrovascular cores covered by multilayered squamous epithelium. In five cases, there were areas with very delicate fibrovascular cores covered by monolayered epithelial cells. CONCLUSION: The results of this study show that in Uganda, papillary squamous cell carcinoma of the cervix does occur and is predominantly a disease of older women. The results also confirm that papillary squamous cell carcinoma is a distinct subtype with some variants, and support the hypothesis that squamous cell carcinoma of the cervix is heterogeneous group of tumuors.

Adult↗

Cd44: a marker of squamous differentiation in adenosquamous neoplasms.

OBJECTIVE: To test the hypothesis that CD44 standard (CD44[s]) and its other variants, CD44v6 and CD44v7-8, might be useful markers of squamous differentiation in epithelial tumors. DESIGN: We studied expression of CD44(s), CD44v6, and CD44v7-8 using immunohistochemistry in human tumors that had squamous differentiation, glandular differentiation, or both arising in the colon, stomach, esophagus, lung, pancreas, gallbladder, or uterus/cervix, as well as in adjacent nonneoplastic tissues. Formalin-fixed, paraffin-embedded archival tissue specimens of 33 adenosquamous tumors were used. All were stained with monoclonal antibodies against a conserved portion of CD44(s) and its variants, CD44v6 and CD44v7-8, using the avidin-biotin peroxidase method. RESULTS: CD44(s) and its variants consistently and strongly stained areas of tumors with well-developed squamous differentiation. These markers also consistently and strongly stained normal squamous mucosa. Reactivity for CD44 and its variants was lacking in normal glandular type epithelium and in adenocarcinomas composed entirely of well-differentiated mucin-producing glands. Areas of well-differentiated carcinoma, both squamous and adenocarcinoma, were consistent with respect to both extent and intensity of staining. Staining in lymph nodes was similar to that in the primary tumors, with well-differentiated squamous foci being consistently positive, well-differentiated mucin-producing adenocarcinoma foci consistently negative, and poorly differentiated foci showing variable staining. Although staining was less intense with the variants, it followed the same staining pattern as found for CD44(s). No differences in the extent or intensity of staining were identified in the metastatic versus primary tumor foci, nor was any difference identified between superficial and deeply invasive areas of primary tumors. CONCLUSIONS: Our study shows that CD44(s) and its variants are good markers of squamous epithelial differentiation in several types of normal epithelium and tumors, and that these markers can identify areas of well- to moderately differentiated elements in adenosquamous neoplasms. However, poorly differentiated tumors show an inconsistent staining pattern with CD44, such that it cannot be used as a reliable and practical marker of squamous differentiation in poorly differentiated neoplasms.

Adenocarcinoma↗