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PubMed1990

Detection of human papillomavirus DNA in squamous bronchial metaplasia and squamous cell carcinomas of the lung by in situ hybridization using biotinylated probes in paraffin-embedded specimens.

We examined a series of paraffin-embedded tissue specimens from 10 cases of squamous bronchial metaplasia and 33 cases of squamous cell carcinoma of the lung for histologic characteristics and for the presence and typing of human papillomavirus (HPV) by molecular in situ hybridization with biotinylated probes types 6, 11, 16 and 18 under stringent conditions (temperature, 19 degrees C). Fourteen of these lesions (32.5%) showed typical condylomatous histologic changes. Human papillomavirus DNA was present in seven (16%) specimens. Type 6 HPV DNA was detected in one of the squamous bronchial metaplasia cases. In six of the squamous cell carcinomas cases (18%), HPV DNA was identified (type 18, three cases; type 16, one case; type 11, one case; and type 6, one case); one of the squamous cell carcinoma specimens contained both HPV types 16 and 18. Our data confirm the presence of HPV DNA in squamous metaplastic bronchial mucosa and epidermoid lung carcinoma on paraffin-embedded tissues. This suggests that an HPV infection with benign or potentially oncogenic HPV types could be associated not only with genital tumors, but also with bronchial and lung tumors. The role of HPV DNA in the process of malignancy conversion is not yet known; HPV DNA could possibly be a cocarcinogenic factor. In situ hybridization with biotinylated probes is a useful and appropriate method of retrospective analysis of HPV DNA sequences in routinely paraffin-embedded lesions. It may be used to identify patients at risk of more serious or possibly malignant progression.

Biotin↗

PubMed1998

C-erbB-2 protein expression in oesophageal squamous epithelium from oesophageal squamous cell carcinomas, with special reference to histological grade of carcinoma and pre-invasive lesions.

AIMS: C-erbB-2, an oncogene, is member of the growth factor receptor family. Its role in activation of oesophageal squamous cell carcinoma is poorly understood. The aim of this study was to evaluate the part played by c-erbB-2 in oesophageal squamous cell carcinoma in Hong Kong Chinese patients. METHODS: We examined the expression of the c-erbB-2 oncoprotein in 104 oesophageal squamous cell carcinomas from 89 men and 15 women, ranging in age from 41 to 89 years (mean 63). C-ercB-2 expression was studied with monoclonal antibody, using an antigen retrieval method. RESULTS: Focal c-erbB-2 membrane staining was present in 10 (10%) of 104 squamous cell carcinomas. Staining was also noted in the adjacent dysplastic epithelium (n=2) and non-tumour inflamed epithelium (n=2). In carcinomas, the c-erbB-2 membrane staining was identified only in superficial well-differentiated tumour cells and the expression did not predict biological behaviour. CONCLUSIONS: We conclude that the c-erbB-2 oncoprotein is expressed in a portion of oesophageal squamous cell carcinomas and precursor lesions. This suggests that c-erbB-2 activation plays a certain role, mostly probably during the early stages, in carcinogenesis in oesophageal squamous cell carcinomas from Hong Kong Chinese patients.

Adult↗

PubMed1998

A study of a new tumour marker, CYFRA 21-1, in squamous cell carcinoma of the head and neck, and comparison with squamous cell carcinoma antigen.

CYFRA 21-1 (CYFRA) is a newly developed tumour marker which is useful in evaluating large cell lung carcinoma, especially the squamous cell type. The purpose of this study was to assess the clinical value of CYFRA for squamous cell carcinoma of the head and neck and compare the results with squamous cell carcinoma antigen (SCCA). Serum levels of CYFRA were measured in 168 patients with a newly diagnosed head and neck squamous carcinoma. In addition, 77 patients without evidence of neoplasm were included as controls. At the same time, SCCA was also determined. The cut-off values of CYFRA and SCCA, determined at the 95th percentile of the standard Gaussian variate of controls, were 2.48 ng/ml and 1.49 ng/ml respectively. The diagnostic sensitivity of CYFRA was superior to that of SCCA, especially for nasopharyngeal carcinoma. The sensitivity of CYFRA for nasopharyngeal carcinoma was much higher (58.3%) than that of SCCA (15.5%). However, the sensitivity of CYFRA is not satisfactory in all types of squamous carcinoma. For oral cancer, the sensitivity is only 25.6%. CYFRA is a useful serum marker for patients with certain types of head and neck squamous carcinoma, such as nasopharyngeal carcinoma and hypopharyngeal carcinoma. In addition, CYFRA may be also useful in monitoring recurrence of certain types of SCCHN, which are sometimes difficult to detect.

Antigens, Neoplasm↗

PubMed1998

Telomerase expression in normal epithelium, reactive atypia, squamous dysplasia, and squamous cell carcinoma of the uterine cervix.

Telomerase activity has been detected in a broad range of human malignant neoplasms, and its expression may represent an essential step in the malignant transformation of tissues; however, the expression of telomerase in premalignant lesions remains relatively unexplored. We tested tissue sections of cervical squamous cell carcinomas and squamous intraepithelial lesions, samples of benign reactive atypia, and normal cervical mucosa from hysterectomy and cone biopsy specimens for the expression of telomerase. Mirror-image sections from each sample were paraffin embedded and processed for histologic analysis. The test samples of cervical tissue were crushed under liquid nitrogen, and telomerase activity was determined by the telomeric repeat amplification protocol. Telomerase activity was detected in 18 of 18 cases (100%) of invasive squamous cell carcinoma. Twenty-five of 26 samples (96%) of high-grade squamous intraepithelial lesion also tested positively for telomerase activity, including 10 of 10 samples of moderate dysplasia, 12 of 13 samples of severe dysplasia, and 3 of 3 samples of carcinoma in situ. Telomerase activity was detected in 14 of 25 samples (56%) of low-grade squamous intraepithelial lesion and in 10 of 18 samples (56%) of reactive atypia but was detected in only 9 of 50 samples (18%) of histologically normal cervical mucosa. These results suggest that telomerase expression may be a marker of premalignant and malignant squamous cell lesions of the uterine cervix, although it is also expressed in a high proportion of cases of reactive atypia.

Carcinoma, Squamous Cell↗

PubMed1983

Mucoepidermoid and squamous cell carcinomas of breast with reference to squamous metaplasia and giant cell tumors.

Clinical and pathologic features of five low-grade mucoepidermoid and a similar number of squamous cell carcinomas of breast are presented. Three of each were retrieved from 55 cases of invasive breast cancer previously assessed to exhibit squamous metaplasia. Although the estimated incidence of low-grade mucoepidermoid cancers is approximately 0.2%, they may be more frequent, masquerading under designations of squamous metaplasia or intracystic carcinomas. All patients with low-grade mucoepidermoid cancer, and the two recorded previously, were free of recurrence for 4-10 years. No high-grade mucoepidermoid cancers were found. Squamous cell cancers frequently have a phyllode configuration (carcinoma phyllodes). Two examined by electron microscopy revealed a commonality of ultrastructural features with similar tumors of other sites. None exhibited glandular differentiation or tinctorial evidence of mucin secretion. One squamous cell carcinoma contained both malignant epithelial and banal, osteoclast-like, stromal giant cells. Only the latter were identified in tissue culture. This experience and review of the literature prompted a nosologic characterization of giant cell lesions of breast. One patient with squamous cell carcinoma succumbed because of her disease; the remainder are either free of or alive with recurrence at 4 and 10 years.

Adult↗

PubMed2005

Pulmonary squamous cell carcinoma following head and neck squamous cell carcinoma: metastasis or second primary?

PURPOSE: To distinguish a metastasis from a second primary tumor in patients with a history of head and neck squamous cell carcinoma and subsequent pulmonary squamous cell carcinoma. EXPERIMENTAL DESIGN: For 44 patients with a primary squamous cell carcinoma of the head and neck followed by a squamous cell carcinoma of the lung, clinical data, histology, and analysis of loss of heterozygosity (LOH) were used to differentiate metastases from second primary tumors. RESULTS: Clinical evaluation suggested 38 patients with metastases and 6 with second primaries. We developed a novel interpretation strategy based on biological insight and on our observation that multiple LOH on different chromosome arms are not independent. LOH analysis indicated metastatic disease in 19 cases and second primary squamous cell carcinoma in 24 cases. In one case, LOH analysis was inconclusive. For 25 patients, LOH supported the clinical scoring, and in 18 cases, it did not. These 18 discordant cases were all considered to be second primary tumors by LOH analysis. CONCLUSIONS: A considerable number of squamous cell lung lesions (50% in this study), clinically interpreted as metastases, are suggested to be second primaries by LOH analysis. For these patients, a surgical approach with curative intent may be justified.

Adult↗

PubMed1999

Nitric oxide synthase type 3 is increased in squamous hyperplasia, dysplasia, and squamous cell carcinoma of the head and neck.

The implication of nitric oxide (NO*) in the multistep process of carcinogenesis prompted us to examine the expression of endothelial constitutive nitric oxide synthase (NOS3) in head and neck squamous cell carcinoma (HNSCCa). Eleven paraffin-embedded samples of normal oral mucosa, 3 reactive oral lesions, 13 samples of squamous dysplasia, and 120 specimens of HNSCCa were immunostained with an anti-NOS3 monoclonal antibody and graded on a 0 to 4+ scale of intensity. Normal squamous mucosa demonstrated very little NOS3 expression. Areas of normal mucosa, reactive mucosa, and dysplastic lesions associated with inflammation tended to demonstrate regional expression of NOS3. Reactive mucosal lesions, squamous dysplasia, and HNSCCa demonstrated a significant (p<.0001) increase in global expression of NOS3. Therefore, NOS3 is expressed very little in histologically normal squamous mucosa, while squamous hyperplasia, dysplasia, and HNSCCa express significantly more NOS3. Regional variation in NOS3 expression appears to be associated with perilesional inflammation.

Antibodies, Monoclonal↗

PubMed2004

Regulation of squamous cell carcinoma antigen production by E-cadherin mediated cell-cell adhesion in squamous cell carcinoma cell line.

Squamous cell carcinoma antigen (SCCA) is a useful tumor marker for diagnosis and management of squamous cell carcinoma. It is well known that cell-cell adhesion is important for progression of cancer. However, it is not clarified whether cell-cell adhesion affects SCCA production in squamous cell carcinoma. The present study was, therefore, undertaken to investigate whether E-cadherin-mediated cell-cell adhesion affects SCCA production in squamous cell carcinoma of the uterine cervix. SKG-IIIa cells or CaSki cells, cervical squamous cell carcinoma cell lines, were treated with anti-E-cadherin antibodies (1 microg/ml) up to 72 h. The cells were dissociated, and SCCA content in the cytosol and SCCA mRNA levels were significantly decreased compared to the control group treated with mouse IgG. Secondly, the signaling pathway for SCCA production mediated by E-cadherin was examined. Phosphatidylinositol (PI) 3-kinase is a well-known mediator of E-cadherin-mediated biological events. The treatment with a PI 3-kinase inhibitor suppressed SCCA production in SKG-IIIa cells. It is concluded that E-cadherin mediated cell-cell adhesion maintains SCCA production through PI 3-kinase in squamous cell carcinoma.

Antibodies, Neoplasm↗

PubMed2006

Different expression patterns of intact forms of squamous cell carcinoma antigens between normal and malignant cervical squamous epithelial tissues: nondenaturing polyacrylamide gel electrophoretic analysis.

Squamous cell carcinoma antigen (SCCA), a 45-kDa tumor-associated serpin, mainly consists of two highly homologous molecules, SCCA1 and SCCA2, which possess unique proteinase inhibitory properties. Importantly, our previous study demonstrated that an intact structure of SCCAs, and not a cleaved form yielded by interacting with target proteinase, is essential for their function as a serpin. The aim of this study is therefore, to develop a simple method of analyzing expression patterns of intact forms of SCCAs (functional SCCAs) in cervical squamous epithelial tissues and to investigate whether there are any differences in the expression of intact forms of SCCAs between normal and malignant cervical squamous epithelial tissues. We used nondenaturing polyacrylamide gel electrophoresis (PAGE) with immunoblotting. The newly generated antibody, Pab Y2, recognizes only intact form of SCCAs, while the conventional antibody, Mab 27, reacts with the cleaved form of SCCA1 as well as intact forms of SCCAs. Nondenaturing PAGE using Pab Y2 showed that an intact form of SCCAs in the heat-treated tissue extract at 60 degrees C for 2 h was separated into at least five bands, termed as bands A-E from cathode to anode. By comparison with two-dimensional electrophoresis patterns of SCCAs, it was found that the first three bands, i.e. bands A-C, are derived from the intact form of SCCA1, while the other two bands, i.e. band D and E are from the intact form of SCCA2. Specifically, band E, but not band D, of SCCA2 is apparently increased in squamous cell carcinomas compared with normal squamous epithelium. In conclusion, this novel analytical approach will be useful for investigating the different expression patterns of functional SCCAs between normal and malignant cervical squamous epithelial tissues.

Antigens, Neoplasm↗

PubMed1991

Clinical usefulness of serum squamous cell carcinoma antigen for early detection of squamous cell carcinoma arising in mature cystic teratoma of the ovary.

Squamous cell carcinoma arising in mature cystic teratoma of the ovary is rarely diagnosed preoperatively. We measured the pre-treatment serum levels of squamous cell carcinoma antigen in three stage I patients in order to evaluate its usefulness as a tumor marker for early detection of the disease. The serum levels were elevated in each case, to 26.9, 5.1, and 3.2 ng/mL, respectively, and rapidly dropped to within the normal range after treatment. All patients are recovered and show no evidence of recurrence, and the levels of serum squamous cell carcinoma antigen have remained within normal limits. These results suggest that measurement of the serum squamous cell carcinoma antigen level may be useful in diagnosing an early-stage primary squamous cell carcinoma arising in a mature cystic teratoma of the ovary. An elevated preoperative serum level of squamous cell carcinoma antigen may indicate the need for a rapid pathologic examination of the tumor to look for malignant elements and may influence the surgical regimen.

Adult↗

PubMed1990

Squamous cell carcinoma antigen in oral squamous cell carcinomas.

Squamous cell carcinoma (SCC) antigen is a tumor-associated antigen isolated from the squamous cell carcinoma of the uterine cervix. In order to estimate the usefulness of the SCC antigen in monitoring the clinical behaviors of oral squamous cell carcinomas, we analyzed clinicopathologically and immunohistochemically 54 cases of squamous cell carcinoma of the oral cavity. Elevated serum SCC antigen levels were detected in 23 (42.6%) out of 54 oral squamous cell carcinomas. The positive rate of serum SCC antigen levels was significantly higher in the patients with advanced clinical stages and poorly differentiated carcinoma. The serum levels declined rapidly after the surgical operation. It is considered that the serum SCC antigen levels could be useful in monitoring the extension, effectiveness of therapy, recurrence and metastases of the oral squamous cell carcinomas. Immunohistochemically, strong staining was seen in the cytoplasm of the well-differentiated carcinoma cells.

Antigens, Neoplasm↗

PubMed1984

[Prostatic squamous cell cancer and its differential diagnostic contrast with squamous cell metaplasia].

Thirteen (2.2%) squamous-cell carcinomas were found among 600 autopsy cases of prostatic carcinoma. In the surgical material squamous-cell carcinoma was observed in 3 cases (1.7%). Clinical and morphological analysis of these 16 cases together with the published observations shows squamous-cell carcinoma of the prostate to have a grave clinical course and bad prognosis. One observation of the erroneous histologic diagnosis of carcinoma in case of squamous-cell duct and gland metaplasia of the prostate is reported. The differential-diagnostic differences between dyshormonal squamous-cell metaplasia and squamous-cell carcinoma of the prostate are described.

Adenocarcinoma↗

PubMed2003

Reporting of atypical squamous cells, cannot exclude a high-grade squamous intraepithelial lesion (ASC-H) on cervical samples: is it significant?

"Atypical squamous cells, cannot exclude a high-grade squamous intraepithelial lesion (ASC-H)" is a new diagnostic category in the 2001 Bethesda nomenclature system for cervical cytology. The purpose of this 7-mo retrospective study (March 1, 2002-September 30, 2002) was to evaluate the significance of ASC-H on cervical Thin Prep Pap Tests. During this period, 25 (0.27%) of 9,214 Pap Tests were diagnosed as ASC-H, 22 of which resulted in either follow-up cervical biopsies and/or cervical cones, and which formed the basis of this study. Tissue specimens (22 cases) were negative in 5 cases (23%) and positive in 17 cases (77%). Of the positive specimens, there were 2 (12%) low-grade squamous intraepithelial lesions (LSIL) and 15 (88%) high-grade squamous intraepithelial lesions (HSIL). Of the 22 cases, ASC-H diagnoses included immature/atypical squamous metaplasia vs. a squamous intraepithelial lesion (SIL) in 19 (86%) cases, and tight clusters of small cells with a high nuclear to cytoplasmic ratio in 3 (14%) cases. The results of this study indicate that the reporting of ASC-H on cervical samples does lead to the detection of HSILs in a significant number of cases (68% in this study). Therefore, further evaluation of the patient is warranted.

Adult↗

PubMed1997

[Basaloid squamous epithelial carcinoma (basaloid-squamous carcinoma) of the mouth floor. Differential diagnosis and response to neoadjuvant chemotherapy].

The basaloid squamous cell carcinoma (BSCC) is a variant of squamous cell carcinoma, having histologically distinctive features and appearing in the oral cavity, upper respiratory tract and esophagus. Histological hallmarks are the presence of a basaloid component in intimate association with squamous cell carcinoma. The basaloid component is characterized by tightly packed nests of cells with scant cytoplasm and hyperchromic nuclei without visible nucleoli and an increased mitosis rate. Basaloid squamous cell carcinoma is said to have a higher malignant potential than common oral squamous cell carcinoma with an increased incidence of regional lymph-node metastases and distant metastases. Our finding of a Ki-67 index of 30% and the immunohistochemical demonstration of p53 protein speaks well for enhanced aggressive biological behavior. The differential diagnosis includes the adenoid cystic, mucoepidermoid, neuroendocrine, adenosquamous and conventional oral squamous cell carcinoma. Because of early dissemination, radical surgical treatment and additional radiation therapy are considered necessary. Our findings indicate that partial clinical and histological tumor regression occurs after systemic neoadjuvant chemotherapy.

Biomarkers, Tumor↗

PubMed1993

Morphological comparison between benign keratinizing cystic squamous cell tumours of the lung and squamous lesions of the skin in rats.

Approximately 700 cases of keratinizing cystic squamous lung lesions in rats were investigated by light microscopy in order to clarify the nomenclature and classification of these lesions. The structure of benign keratinizing cystic squamous cell tumours of the lung was compared to that of cystic squamous lesions in the skin of rats, with consideration of data from the literature. We conclude that the reviewed keratinizing cystic squamous cell lesions of the lung are true neoplasms and that the growth pattern of these cystic lesions is inconsistent with that of a simple cyst. In the development of squamous lung cancer, a continuum of proliferation from exaggerated metaplasia through benign cystic tumours to invasive squamous cell carcinomas can be observed.

Animals↗

PubMed1988

Posttraumatic lobular squamous metaplasia of breast. An unusual pseudocarcinomatous metaplasia resembling squamous (necrotizing) sialometaplasia of the salivary gland.

Squamous metaplasia arising in nonneoplastic breast parenchyma is reportedly rare. We present a unique case which occurred following severe blunt trauma to the right breast of a 59-yr-old woman. The lesion contained sheets of squamous cells with a lobular growth pattern, bland cytology with few mitoses, and keratin and keratohyalin granules. It bore a striking resemblance to squamous (necrotizing) sialometaplasia of the salivary gland in that it exhibited lobular, pseudocarcinomatous growth. The patient has remained free of disease 49 mo after segmental resection of the lesion. Four previous cases of squamous metaplasia of the female breast have been reported, though none presented with a history of trauma or previous surgical manipulation. It is important to differentiate this entity from pure squamous cell carcinoma, and metaplastic change in ductal breast carcinoma, fibroadenoma, and other lesions. Breast aspiration biopsies revealing squamous cells cannot exclude carcinoma; thus, caution must be exercised.

Breast↗

PubMed1993

Basaloid squamous carcinoma of the head and neck. Immunohistochemical comparison with adenoid cystic carcinoma and squamous cell carcinoma.

Basaloid squamous carcinoma (BSC) is a rare distinct variant of squamous cell carcinoma of the head and neck region. This entity may commonly pose diagnostic difficulties, especially on small biopsy material. We report the clinicopathological characteristics of 12 new cases and compare their immunohistochemical features with those of solid adenoid cystic carcinomas and conventional squamous cell carcinomas. Our results show that neoplastic BSCs and squamous cell carcinomas do not react to vimentin and S100 protein, while adenoid cystic carcinomas manifest both. The BSCs, however, are S100 protein-positive in intratumoral dendritic Langerhans' cells that are lacking in squamous cell and adenoid cystic carcinomas. Our findings indicate that the immunohistochemical differences between BSC and adenoid cystic carcinoma could assist in their differential diagnosis.

Aged↗

PubMed1999

Histology correlation with atypical squamous cells of undetermined significance (ASCUS) and low-grade squamous intraepithelial lesion (LSIL) cytology diagnoses: An argument to ensure ASCUS follow-up that is as aggressive as that for LSIL.

The purpose of the present study was to compare histology outcomes of cytological atypical squamous cells of undetermined significance (ASCUS) to the histology outcomes of cytological low-grade squamous intraepithelial lesion (LSIL). Cases with a cytology diagnosis of ASCUS and LSIL that had correlative histology obtained within 3 mo of the cervico-vaginal smear were accrued from the files of the Cytology and Histology Departments of Mercy Hospital Medical Center (Des Moines, IA). All of the cytology cases were examined by a cytotechnologist, a cytopathologist, and the histopathologist who signed out the biopsy material. The laboratory's benign: ASCUS: LSIL: HSIL + ratio was 94.0%: 3.8%: 1.5%: 0.7% for the time period of this analysis; its ASCUS:SIL proportion was 1.76. Histology correlations to 249 ASCUS cases showed 45 (18%) CIN2s (cervical intraepithelial neoplasm 2) or CIN3s, 134 (54%) CIN1s, and 70 (28%) nonneoplastic biopsies. Ten of 24 (42%) ASCUS cases that showed histological CIN3 and seven of 21 (33%) ASCUS cases that showed histological CIN2 contained atypical immature squamous metaplastic cells, while the remainder showed squamous cells with mature, superficial/intermediate-type cytoplasm. Histology correlations to 576 LSIL cases showed 96 (17%) CIN2s or CIN3s, 397 (69%) CIN1s, and 83 (14%) nonneoplastic biopsies. One hundred forty-six (59%) ASCUS and 424 (74%) LSILs had histological koilocytosis with nuclear atypia (KA); the sole histological finding of KA was seen among 76 (30.5%) ASCUS and 146 (25.3%) LSIL cases. The majority of cytological ASCUS and LSIL cases selected by clinicians for biopsy have histological CIN and a substantial minority show CIN2 and CIN3, which, in the case of ASCUS, is frequently associated with atypical immature squamous metaplastic cells. There is a high prevalence of histological KA among ASCUS and LSIL cases. Diagn. Cytopathol. 21:292-295, 1999.

Cervix Uteri↗