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PubMed1995

Basaloid-squamous carcinoma of the nasopharynx. An Epstein-Barr virus-associated neoplasm compared with morphologically identical tumors occurring in other sites.

BACKGROUND: Basaloid-squamous carcinoma is a newly characterized, highly aggressive neoplasm occurring mostly in the base of tongue, hypopharynx, larynx, and esophagus. Its occurrence in the nasopharynx is rare. METHODS: The clinicopathologic features of three cases of basaloid-squamous carcinoma of the nasopharynx are described and were studied for the presence of Epstein-Barr virus (EBV) by in situ hybridization for EBV-encoded small nuclear RNA (EBER). For comparison, basaloid-squamous carcinomas occurring in other sites also were studied for the presence of EBV. RESULTS: EBER was detected in all 3 cases of basaloid-squamous carcinoma occurring in the nasopharynx, but in none of the 13 cases from other sites including the esophagus, larynx, pharynx, hypopharynx, and nasal cavity. The nasopharyngeal basaloid-squamous carcinomas occurred in two male and one female patients with an age range of 48-70 years. The serum immunoglobulin A against the EBV-viral capsid antigen was elevated in all three cases. Two patients developed cervical lymph node involvement during the course of the disease. All three patients were treated by radiotherapy and survived for longer than 34 months compared with the average reported median survival of approximately 2 years for basaloid-squamous carcinomas occurring in the usual sites. CONCLUSION: Based on this limited study, basaloid-squamous carcinoma occurring in the nasopharynx appears to be an EBV-associated neoplasm, whereas the same tumor occurring in other sites is not. The prognosis is potentially better for patients with nasopharyngeal basaloid-squamous carcinoma, which appears to be pathogenetically and biologically more related to the much more common nasopharyngeal undifferentiated carcinoma.

Aged↗

PubMed2001

Cutaneous squamous cell carcinoma and p53 codon 72 polymorphism: a need for screening?

The association between human papillomavirus (HPV)-associated cervical cancer and cutaneous squamous cell carcinoma and codon 72 polymorphism in the p53 gene is not unequivocal. Especially, it is not known whether carriers of the arginine form have an increased risk of cancer that necessitates screening. The alternative is that the polymorphism is a tumor marker instead of a risk factor. We set out a case-control study to determine the risk of squamous cell carcinoma of the skin in individuals with the p53 codon 72 arginine genotype in order to establish the possible need for screening. The distribution of the different p53 codon 72 genotypes was examined in 86 subjects with a history of cutaneous squamous cell carcinoma and in 168 controls. Additionally, 121 subjects who had had histologically proven basal cell carcinoma and 108 subjects who had had non-familial malignant melanoma were tested. p53 polymorphism was evaluated by polymerase chain reaction (PCR) using DNA samples from peripheral blood lymphocytes. In a subgroup of patients with squamous cell carcinoma and controls, the presence of epidermodyplasia verruciformis human papillomavirus (EV-HPV) DNA was determined in plucked eyebrow hair. Differences in the distributions of the genotypes among cases and controls were calculated, and univariate and multivariate analyses were performed to assess the risk to develop cutaneous squamous cell carcinoma in the presence of the p53 codon 72 arginine genotype. Frequency distributions of the three different genotypes (homozygous for the arginine allele, heterozygous for the two alleles, and homozygous for the proline allele) were similar among the squamous cell carcinoma group and the control group: 47.1%, 46.0% and 6.9% versus 47.8%, 45.8% and 6.4%, respectively. Statistical analysis showed no significant differences between these groups. In patients with squamous cell carcinoma and controls who harbored EV-HPV DNA in their plucked eyebrow hair, similar results were obtained. The distributions of the p53 codon 72 genotypes in the basal cell carcinoma and malignant melanoma group were also not significantly different from the control group. p53 codon 72 arginine homozygosity does not appear to represent a significant risk factor for cutaneous squamous cell carcinoma and screening seems not to be indicated. Mol. Carcinog. 30:56-61, 2001.

Adult↗

PubMed2006

The utility of GLUT-1 immunolocalization in cell blocks: An adjunct to the fine needle aspiration diagnosis of cystic squamous lesions of the head and neck.

BACKGROUND: Cytologic distinction of metastatic cystic squamous cell carcinoma (SCC) from benign squamous cell lesions, especially the ones with superimposed inflammatory atypia, can be very challenging. The authors evaluated the usefulness of glucose transporter-1 (GLUT-1) immunostaining as an adjunct to fine-needle aspirations of squamous lesions of the head and neck. METHODS: Immunohistochemical staining for GLUT-1 was performed on paraffin-embedded cell blocks of 28 cases with the following cytologic diagnoses: 1) metastatic SCC (11 cases); 2) atypical squamous cells, SCC [corrected] cannot be excluded (6 cases); and 3) cytologic findings consistent with branchial cleft cyst (BCC) (11 cases). RESULTS: All 11 cases with an unequivocal cytologic diagnosis of metastatic SCC were positive for GLUT-1. Tissue follow-up confirmed metastatic SCC in all 11 cases. The squamous cells in all 11 cases with cytologic findings consistent with BCC were negative for GLUT-1; tissue follow-up confirmed diagnoses of BCC in 8 cases. In the remaining 3 cases, excision was not performed, and, clinically, no recurrences were identified at 28, 20, and 16 months of follow-up. Of the 6 cases with cytologic diagnosis of atypical squamous cells, 3 were negative and 3 were positive for GLUT-1. Subsequent excisional biopsies in these cases revealed 4 cases of metastatic SCC (3 positive and 1 negative for GLUT-1), 1 case of BCC (negative for GLUT-1), and 1 case of thyroglossal duct cyst (negative for GLUT-1). CONCLUSION: GLUT-1 immunostaining is a useful adjunct in differentiating benign and malignant squamous lesions in cell-block material. Although negative staining for GLUT-1 does not exclude malignancy, positive immunoreactivity for GLUT-1 may aid in accurate diagnosis of malignancy in cytomorphologically equivocal squamous lesions of the head and neck.

Biopsy, Fine-Needle↗

PubMed2001

A comparison of ovarian metastasis between squamous cell carcinoma and adenocarcinoma of the uterine cervix.

OBJECTIVE: The purpose of our study was to investigate a possible difference in ovarian metastasis between squamous cell carcinoma and adenocarcinoma of the uterine cervix and to confirm clinicopathological variables associated with the metastases. METHODS: Clinical and pathological variables of 1064 patients with invasive squamous cell carcinoma and 240 with adenocarcinoma were studied. RESULTS: Ovarian metastasis was found in 14 patients (1.3%) with squamous cell carcinoma and 15 (6.3%) with adenocarcinoma. The mean age of patients with ovarian metastasis of squamous cell carcinoma was 57.4 years, compared to 50.2 years for adenocarcinoma. Ovarian metastasis of adenocarcinoma was more likely to be visible (40.0%) and present in both ovaries (66.7%), while these two characteristics occurred in only 21.4 and 36.7% of patients with squamous cell carcinoma. A logistic regression analysis with clinical variables indicated that clinical stage beyond IIb was a significant variable of squamous cell carcinoma, and more than 30-mm tumor size was significant in adenocarcinoma. CONCLUSION: The incidence of ovarian metastasis of adenocarcinoma of the uterine cervix was significantly higher than that of squamous cell carcinoma. The incidence of adenocarcinoma was associated more closely with tumor size than clinical stage, whereas it was more associated with clinical stage in squamous cell carcinoma. The results thus suggested that the differences in ovarian metastases were caused by the different characteristics of the two types of carcinoma.

Adenocarcinoma↗

PubMed2001

Adenosquamous and squamous carcinoma of the colon and upper rectum: a clinical and histopathologic study.

PURPOSE: Squamous and adenosquamous carcinoma of the colon and proximal rectum are rare neoplasms in which the clinicopathologic behavior and the most appropriate management are unknown. The purpose of this study was to review the histology and clinical course of the largest series of cases ever reported from a single center on this rare condition. METHOD: The Mayo Clinic tissue registry was searched for all primary cases of squamous and adenosquamous carcinoma of the colon or rectum proximal to 8 cm from the dentate and presenting before December 31, 1992. Of the 52 identified cases there was adequate histologic material for review in 44 cases. These cases were divided into pure squamous-cell carcinoma (n = 11), mixed adenosquamous carcinoma (n = 31), and adenocarcinoma with benign-appearing squamous metaplasia (adenoacanthoma; n = 2). Squamous-cell carcinomas were examined for evidence of human papilloma virus by in situ hybridization. A retrospective review of medical records was undertaken in all 52 cases with respect to predisposing factors, clinicopathologic behavior, prognostic features, and treatment with adjuvant therapy. RESULTS: The charts of 52 patients (20 females), with a mean age of 58.6 (range, 19-90) years, were reviewed. Right-sided lesions were the most common (43 percent). Metastatic disease was evident at presentation in 49 percent of patients, the most common sites in order being liver, peritoneal, and lung. The five-year overall survival rate was 34 percent, Stage I to III disease had a 65 percent five-year survival rate, and Stage IV mean survival time was 8.5 months. For node-positive and node-negative disease, 23 and 85 percent, respectively, survived five years. There was no evidence of human papilloma virus in the six squamous-cell carcinomas examined. CONCLUSION: Squamous and adenosquamous carcinomas of the colon and rectum are rare neoplasms. Although a poor prognosis can be expected for node-positive disease, patients with negative nodes do generally the same as patients with adenocarcinoma histology. Based on advances made with multimodality therapy of squamous-cell cancer of the anus and adenocarcinoma of the rectum, further studies should define the role of postoperative therapies for these lesions.

Adenocarcinoma↗

PubMed2004

Radiotherapy for locally advanced basal cell and squamous cell carcinomas of the skin.

PURPOSE: To determine the outcomes of patients with locally advanced basal cell and squamous cell carcinomas of the skin treated with radiotherapy. METHODS AND MATERIALS: A retrospective review of the outcomes of patients with basal cell and squamous cell carcinomas treated with radical radiotherapy was conducted. Patients with T2 or more advanced disease or nodal disease were included. The clinical course after radiotherapy and factors that can affect locoregional control were analyzed. RESULTS: Four-year locoregional controls for basal cell and squamous cell carcinomas are 86% and 58%, respectively. The median time to recurrence of basal cell and squamous cell carcinomas are 40.5 months and 5.0 months, respectively. No deaths resulted from basal cell carcinomas, but 65% (30/46) of all patients with locoregional recurrent squamous cell cancers died from the disease. Uncontrolled locoregional disease was the cause of death in 81% (30/37) of all patients who died of squamous cell cancers. CONCLUSIONS: Basal cell carcinomas can be well controlled with radiotherapy even when locally advanced. Squamous cell carcinomas have a much poorer outcome and can recur quickly after radiotherapy. Locoregional failure remains the predominant cause of death in recurrent squamous cell carcinomas.

Adult↗

PubMed2000

Matrix metalloproteinases and tissue inhibitors of metalloproteinases in bronchial squamous preinvasive lesions.

Metalloproteinases and their inhibitors are known to play an important role in the extracellular matrix remodeling associated with preinvasive lesions and invasive carcinomas; however, little is known about their role in early lung carcinoma. Immunohistochemical studies were made of the reactivity of bronchial squamous preneoplastic lesions from cigarette smokers, including basal cell hyperplasia, squamous metaplasia, dysplasia, carcinoma in situ, and invasive squamous cell carcinoma for matrix metalloproteinases (MMPs), their tissue inhibitors (TIMPs), and type IV collagen in 13 patients. Staining for type IV collagen disclosed discontinuities in basement membranes from basal cell hyperplasia to dysplasia, progressing to destruction in carcinoma in situ and invasive carcinoma. Reactivity for MMP-9 was mild in basal cell hyperplasia and squamous metaplasia, increasing in carcinoma in situ and invasive carcinoma. In contrast, reactivity for MMP-1 was strong in basal cell hyperplasia and squamous metaplasia, decreasing in carcinoma in situ and invasive carcinoma. Some neoplastic cells in carcinoma in situ and invasive carcinoma were MMP-3 positive. Staining for MMP-2 and TIMP-1 was moderate to strong in all squamous preinvasive lesions. Confocal microscopy showed MMP-9-positive cells passing through fragmented basement membranes in which type IV collagen and MMP-9 were colocalized. Type IV collagen colocalized with MMP-2 in all lesions and with TIMP-1 in basal cell hyperplasia and squamous metaplasia. The inverse relationships between the reactivity for MMP-1 and MMP-9 with progression of bronchial squamous preinvasive lesions suggest important roles for these MMPs in basement membrane remodeling in these lesions.

Aged↗

PubMed2003

Endocrine tumors of the uterine cervix: incidence, demographics, and survival with comparison to squamous cell carcinoma.

OBJECTIVE: The aim was to describe the epidemiology of endocrine tumors of the cervix in comparison with invasive squamous cell carcinomas using population-based data reported to the Surveillance, Epidemiology and End-Results (SEER) program. METHODS: Retrospective analysis of actively followed cases reported to SEER from 1973 to 1998. Incidence, demographic characteristics, and survival were compared for endocrine and squamous tumors. RESULTS: There were 239 cases of endocrine tumors and 18,458 cases of invasive squamous cell carcinoma of the cervix included in the study. Mean age at diagnosis was 49 years for endocrine tumors versus 52 years for squamous cell carcinoma (P < 0.01). Endocrine tumors were more likely to present at a later FIGO stage (P < 0.01), and to have lymph node involvement at diagnosis (57 vs 18%, P < 0.01) compared to squamous cell carcinoma. Observed median survival for women with endocrine tumors was 22 months versus 10 years for women with squamous cell carcinoma. Age and FIGO stage-adjusted hazards of death were 1.84 times greater for endocrine tumors than for squamous cell carcinoma (95% CI 1.52-2.23). At all stages of disease, survival was worse for women with endocrine tumors compared to women with squamous cell carcinomas. CONCLUSIONS: Endocrine tumors of the cervix are extremely aggressive and survival is poor regardless of stage at diagnosis.

Adult↗

PubMed2002

Keratinising squamous metaplasia of the bladder: natural history and rationalization of management based on review of 54 years experience.

OBJECTIVE: To review our experience of keratinising squamous metaplasia of the bladder as a predictor for the development of cancer and other complications, and formulate a policy for its management. MATERIALS AND METHODS: A retrospective review (1945-1999) identified 34 patients with histologically proven keratinising squamous metaplasia (27 males and 7 females, average age 50 years, range 13-80 years). The histological criteria used to diagnose keratinising squamous metaplasia were squamous metaplasia of the urothelium with keratinisation and/or hyperkeratosis and/or acanthosis. Female patients with non-keratinising squamous metaplasia (vaginal metaplasia) were excluded. RESULTS: Four patients had synchronous bladder carcinoma (three advanced with early death; one localised, cured by cystectomy). Another 14 patients had extensive metaplasia (Group A, >50% of mucosal involvement). Three cases had cystectomy and cure. Six cases (out of 11) developed subsequent cancer (4 advanced and early death, two localised and cured by cystectomy). One other case died of obstructive uropathy secondary to squamous metaplasia. Two cases died of unrelated causes. Sixteen patients had limited squamous metaplasia (Group B, <50% involvement mucosal surface). Twelve patients had endoscopic resection, extraction bladder calculus etc. with no further complications. Another two patients underwent urinary diversion. Two patients (out of 16) developed subsequent cancer both with advanced disease and early death. CONCLUSION: Keratinising squamous metaplasia of the bladder is a significant risk factor for vesical carcinoma and complications, such as bladder contracture and ureteral obstruction. This risk of complications increases with more extensive bladder mucosal involvement. The wide variation in lag time to the development of complications necessitates indefinite follow-up. Selected patients with extensive bladder involvement and long life expectancy should be offered cystectomy.

Adolescent↗

PubMed1997

Mutated and wild-type p53 expression and HPV integration in proliferative verrucous leukoplakia and oral squamous cell carcinoma.

The frequencies of overexpression and mutation in the p53 tumor suppressor gene were examined in proliferative verrucous leukoplakia and oral squamous cell carcinoma with immunohistochemistry and single-strand conformation polymorphism analysis of DNA fragments amplified by polymerase chain reaction. Ten samples each of normal oral mucosa, proliferative verrucous leukoplakia, and squamous cell carcinoma were immunostained with antibodies against p53 protein; 8 of 10 cases of proliferative verrucous leukoplakia cases and 7 of 10 cases of oral squamous cell carcinoma were positive for p53 protein. Minimal staining was observed in normal oral tissues. The quantified labeling indexes demonstrated a range that corresponded to lesion progression. Single-strand conformation polymorphism analysis revealed p53 gene mutations within exons 5 to 8 in 40% (4 of 10) of the squamous cell carcinoma samples. Two of the 4 mutated squamous cell carcinoma samples lacked p53 expression. No p53 mutations were detected in proliferative verrucous leukoplakia tissues. Human papillomavirus 16 was identified in 2 of 7 p53 positive oral squamous cell carcinoma samples. Human papillomavirus 16 and 18 were identified in two of eight p53 positive proliferative verrucous leukoplakia samples. One p53 negative squamous cell carcinoma sample was positive for human papillomavirus 16 and had a mutation in exon 6 of the p53 gene. Human papillomavirus infection along with p53 expression plays a yet to be defined role in the pathogenesis of a limited number of cases of proliferative verrucous leukoplakia and squamous cell carcinoma. p53 immunohistochemistry, p53 gene mutations, and human papillomavirus infection prevalence do not provide a means to differentiate between leukoplakia and carcinoma and do not provide a predictive test for progression of leukoplakia to carcinoma.

Carcinoma, Squamous Cell↗

PubMed1990

Cellular localisation of tumour antigen (TA-4) in normal, dysplastic and neoplastic squamous epithelia of the upper aerodigestive tract.

We report the use of tumour antigen (TA-4) polyclonal antiserum to assess the level and pattern of TA-4 antigen expression in formalin-fixed paraffin-embedded tissue sections from 110 patients with a range of normal, dysplastic and malignant squamous epithelia from various sites in the upper aerodigestive tract. There was a high degree of TA-4 antigen expression in the superficial layers of normal squamous epithelium and in well-differentiated squamous cell cancers (SCC). TA-4 expression was consistently absent in dysplastic oral squamous epithelium and in poorly differentiated SCCs. The degree of cellular heterogeneity in moderately differentiated SCCs was such that morphologically identical squamous cancer cells could be distinguished on the basis of TA-4 expression. Immuno-electron microscopy localised TA-4 antigen to tonofibrils in both normal buccal (squamous) cells and in squamous cancer cells. Results of Western blotting confirmed the presence of a 48 kDa protein consistent with TA-4 antigen in both SCCs and in normal buccal mucosa. We conclude that TA-4 protein is a normal cellular component, that cellular TA-4 expression is related to the level of cellular differentiation in squamous epithelia and that it is not likely to be useful as an independent index of cellular proliferation or malignant behaviour.

Adult↗

PubMed2004

Metalloproteinase-2 expression correlates with aggressiveness of cutaneous squamous cell carcinomas.

Matrix metalloproteinases compose a family of enzymes involved in degradation of the extracellular matrix. Tumor cells must penetrate the basement membrane and traverse the extracellular matrix in order to invade surrounding structures and metastasize to distant sites. Gelatinases, particularly gelatinase A (matrix metalloproteinase-2), demonstrate degradative activity against components of the basement membrane and may be involved in the progression of in situ squamous cell carcinoma lesions. Matrix metalloproteinase-2 overexpression has been correlated with tumor invasiveness and metastasis in a wide variety of cancer types, including squamous cell carcinoma arising on mucous membranes. However, correlation between matrix metalloproteinase-2 overexpression and the spread and prognosis of cutaneous squamous cell carcinoma has not been characterized in the literature at present. In this study, we used immunohistochemical techniques to examine the expression of matrix metalloproteinase-2 in 10 actinic keratosis, 15 in situ, 13 invasive, 13 primary (with documented metastatic disease), 11 metastatic, and 8 recurrent squamous cell carcinoma cases. We found that while the average staining intensity (scale 0-3+, 3+ being strongest) of actinic keratosis and in situ lesions was not statistically significant (0.87-1.3 and 0.75-1.4, respectively), the average staining intensity of invasive squamous cell carcinomas (1.6-2.5) was significantly greater than that of actinic keratosis and in situ lesions. Likewise, while the average staining intensity of primary squamous cell carcinomas and metastatic squamous cell carcinomas was not found to be statistically significant (3.1-3.5 and 3.1-3.8, respectively), the average staining intensity of these lesions was significantly higher than that of invasive lesions. We also found that the intensity of matrix metalloproteinase-2 staining correlates with cellular atypia, inflammation, neovascularization, and the invasive tumor front, as well as tumor aggressiveness, and may play a role in the pathogenesis, invasion, and metastasis of cutaneous squamous cell carcinoma.

Carcinoma, Squamous Cell↗

PubMed2003

Oesophageal squamous cell neoplasia in head and neck cancer patients: upregulation of COX-2 during carcinogenesis.

Patients with (previous) head and neck cancer (HNC) are at high risk for developing second squamous cell cancer of the oesophagus. The role of cyclooxygenase-2 (COX-2) in oesophageal squamous carcinogenesis has not yet been investigated in this high-risk group. Therefore, this study examined COX-2 mRNA and protein expression in oesophageal biopsies and resected tissues of 44 HNC patients. The evaluation covered 55 oesophageal tissue samples (18 invasive oesophageal squamous cell cancers, four high- and eight low-grade dysplasias, 25 normal squamous epithelia) from the 44 patients. mRNA levels of COX-2 were measured by real-time PCR using a LightCycler. COX-2 protein expression was studied immunohistochemically and graded by a staining score. COX-2 mRNA was detected in all samples, and its levels correlated positively with the immunohistochemical staining score (P<0.05). COX-2 expression was upregulated during oesophageal squamous carcinogenesis in HNC patients, that is COX-2 expression increased significantly from normal oesophageal squamous epithelium to low- and high-grade dysplasia and finally to invasive squamous cell cancer (P<0.001). Our findings suggest that COX-2 upregulation contributes to oesophageal squamous carcinogenesis in HNC patients. Prospective studies are needed to evaluate the chemopreventive potential of COX-2 inhibitors in this high-risk group.

Base Sequence↗

PubMed2002

Squamous cell carcinoma arising from a seminal vesicular cyst: possible relationship between chronic inflammation and tumor development.

A case of squamous cell carcinoma arising within an acquired seminal vesicular cyst is described. A 61-year-old man was hospitalized because of hemospermia and dysuria. Under the diagnosis of a left seminal vesicular cyst, surgical resection was performed. Pathological examination revealed squamous cell carcinoma within a seminal vesicular cyst, along with squamous metaplastic foci and severe chronic inflammation. Cell proliferation, determined with reference to MIB-1 labeling indices, showed a stepwise increase from normal columnar epithelium, through squamous metaplasia, to squamous cell carcinoma. Sporadic p53 protein accumulation without evident gene mutations was also apparent in both the carcinoma and squamous metaplastic lesions. We therefore concluded that the squamous cell carcinoma might have developed from squamous metaplastic foci associated with chronic inflammatory stimulation, within a seminal vesicular cyst.

Antigens, Nuclear↗

PubMed2001

Cancer cell expression of urokinase-type plasminogen activator receptor mRNA in squamous cell carcinomas of the skin.

In this study we have used in situ hybridization with radiolabeled antisense RNA probes to examine the expression of mRNA for urokinase-type plasminogen activator and its receptor in histologic samples of squamous cell (n = 7) and basal cell (n = 7) carcinomas of the skin. Messenger RNA for both urokinase-type plasminogen activator and its receptor were expressed in all of the squamous cell carcinomas, but could not be detected in the basal cell carcinomas. In all of the seven squamous cell carcinomas a signal for urokinase-type plasminogen activator receptor mRNA was detected focally in well-differentiated cancer cells surrounding keratinized pearls, and in four specimens urokinase-type plasminogen activator receptor mRNA was in addition expressed by cancer cells at the edge of invasively growing strands of tumor. Urokinase-type plasminogen activator mRNA expression was found in virtually all the cancer cells of the squamous cell carcinomas, and importantly we found, by hybridizations for urokinase-type plasminogen activator and its receptor mRNA on adjacent sections of squamous cell carcinomas, that it was exactly the invading cancer cells that simultaneously expressed both these components required for plasmin-mediated proteolysis at the cell surface. We have previously shown that both urokinase-type plasminogen activator and its receptor mRNA are expressed by the leading-edge keratinocytes in regenerating epidermis during mouse skin wound healing, and that wound healing is impaired in mice made deficient in plasminogen by targeted gene disruption. We propose that there are similarities between the mechanisms of generation and regulation of extracellular proteolysis during skin re-epithelialization and squamous cell carcinoma invasion. The ability of the squamous carcinoma cells to mimic the "invasive" phenotype of re-epithelializing keratinocytes may be one of the factors that make squamous cell carcinomas more aggressive tumors than basal cell carcinomas.

Basal Cell Carcinoma↗

PubMed2002

P63 in pulmonary epithelium, pulmonary squamous neoplasms, and other pulmonary tumors.

p63 is a p53-homologous nuclear protein that appears to play a crucial role in regulation of stem cell commitment in squamous and other epithelia. In this study, p63 expression was examined in benign lung and in neoplasms of pulmonary origin. Eighty sections from routinely fixed and processed archival bronchoscopic biopsy or lobectomy specimens were pretreated with citric acid (pH 6.0) for antigen retrieval, then incubated overnight with anti-p63 monoclonal antibody 4A4. Slides were stained using a streptavidin-biotin kit and diaminobenzidine as chromagen, and were counterstained with hematoxylin. In normal lung, p63 intensely stained nuclei of bronchial reserve cells but did not stain ciliated cells, alveolar epithelial cells, or nonepithelial cells. The lower strata of squamous metaplastic bronchial epithelium stained positively. All squamous-cell carcinomas stained positively (n = 30). In some well-differentiated carcinomas, staining was found at the periphery of tumor nests but was negative in central zones showing squamous maturation. Poorly differentiated carcinomas showed very high proportions (80% to 100%) of p63-positive nuclei. All small-cell carcinomas were p63 negative (n = 9). Staining of bronchioloalveolar carcinomas (n = 7) and adenocarcinomas (n = 23) was variable: some tumors showed no detectable staining, others showed heterogeneously positive staining. Adenosquamous carcinomas (n = 5) displayed a unique basalar staining pattern. Carcinoid tumors were almost entirely negative (n = 5). We conclude that p63 is expressed in benign bronchial stem cells, in neoplastic cells with either squamous differentiation or squamous differentiating potential, and in a subpopulation of adenocarcinomas. p63 immunostaining may also aid in some histopathologic distinctions, such as in small biopsies where the differential diagnosis is poorly differentiated squamous carcinoma versus small-cell carcinoma. A stem cell biology-based classification system for squamous carcinomas is proposed.

Adenocarcinoma↗

PubMed2002

Immunohistochemical localization of growth factors fibroblast growth factor-1 and fibroblast growth factor-2 and receptors fibroblast growth factor receptor-2 and fibroblast growth factor receptor-3 in normal oral epithelium, epithelial dysplasias, and squamous cell carcinoma.

OBJECTIVES: Fibroblast growth factors (FGFs) and their receptors (FGFRs) have been identified in a variety of carcinomas, but there are few studies concerning their presence in oral cancers. The objective of this study was to determine whether FGF-1, FGF-2, and high affinity receptors FGFR2 and FGFR3 are present in the pathogenesis of oral epithelial dysplasias and oral squamous cell carcinoma. STUDY DESIGN: Sections from formalin-fixed, paraffin-embedded samples of oral normal mucosa (n = 14), epithelial dysplasia (n = 20), carcinoma in situ (n = 10), and squamous cell carcinoma (n = 12) were tested for cytoplasmic staining by standard in situ immunohistochemistry with antibodies for FGF-1, FGF-2, FGFR2, and FGFR3. RESULTS: Staining for FGF-1 is decreased or lost in the development of epithelial dysplasia and carcinoma. Staining for FGF-2 showed increased intensity (although not statistically significant) in oral epithelial dysplasias and squamous cell carcinomas and showed a significant increased expression in the upper layers of dysplasias and stratum spinosum-like cells in squamous cell carcinomas. Staining for FGFR2 showed a statistically significant increase in intensity in all layers of epithelial dysplasias and squamous cell carcinomas. Staining for FGFR3 was found in the upper stratum spinosum cells of normal and dysplastic epithelium and well-differentiated squamous cells in squamous cell carcinomas, with a statistically significant increase in staining intensity in dysplastic and carcinomatous tissues. CONCLUSIONS: The loss of FGF-1 is consistent with loss of differentiation in dysplasias and some squamous cell carcinomas. Changes in the localization of FGF-2 and FGFR2 into upper epithelial layers with increasing dysplasia suggest increased mitotic potential of high level cells. The co-localization of FGF-2 and its high affinity receptors in neoplastic tissues suggests an autocrine mechanism of influence on carcinogenesis.

Antibodies↗

PubMed2006

The role of smoking and alcohol intake in the development of high-grade squamous intraepithelial lesions among high-risk HPV-positive women.

BACKGROUND: Infection with human papillomavirus is considered a necessary factor in developing high-grade squamous intraepithelial lesions of the cervix. However, most human papillomavirus positive women do not develop high-grade squamous intraepithelial lesions and other factors may be important for this transition. The objective of the present study was to examine if smoking and alcohol intake are associated with the risk of developing high-grade squamous intraepithelial lesions in women positive for high-risk human papillomavirus types. METHODS: We used baseline information on exposures on 548 high-risk human papillomavirus positive women with normal cytology, comparing 94 women who developed high-grade squamous intraepithelial lesions with 454 women who remained cytologically normal. Logistic regression was applied for statistical analysis. RESULTS: Compared with never smokers, the odds ratio for high-grade squamous intraepithelial lesions among current smokers was 1.99 (95% CI: 1.21-3.28). Among current smokers, number of cigarettes, years of smoking, and early age at smoking initiation were associated with increased risk. However, when modeled simultaneously, it seemed that smoking duration and age at smoking initiation were more associated with risk of high-grade squamous intraepithelial lesions than amount of smoking. Alcohol intake was not associated with risk of high-grade squamous intraepithelial lesions among these women. CONCLUSION: Smoking is associated with an increased risk of developing high-grade squamous intraepithelial lesions in women who are infected with oncogenic human papillomavirus.

Adult↗