Tumor-specific antibodies in sera from patients with squamous cell carcinoma of the uterine cervix

Summary An indirect immunofluorescence assay is described which specifically detects antibodies against cervical carcinoma-associated membrane antigens. Cells from the ME-180 cervical carcinoma cell line were used as target cells. Sera had to be absorbed with pooled tonsillar lymphocytes prior to use, to remove nonspecific antibodies. The antibody was detected in 61 of 74 patients (82%) with invasive squamous cell carcinoma of the uterine cervix and in 5 of 65 controls (8%). A group of 49 patients with early or preneoplastic stages of this tumor (microinvasive carcinoma, carcinome-in-situ, and dysplasia) did not differ from the control group in the incidence of the antibody (5 of 49 patients, 10%). It is concluded that the occurrence of this antibody is specific for cervical carcinoma (P<0.001). However, the assay cannot be used as a diagnostic marker for preneoplastic stages of this tumor.     

Adenocarcinoma of the uterine cervix compared with squamous cell carcinoma: a 12-year study in Southampton and South-west Hampshire

In a 12-year study of the population of Southampton and South-west Hampshire (SSWH), there was no rise or fall in the incidence of adenocarcinoma of the uterine cervix, although the incidence of squamous cell carcinoma fell from 14 to 7.2 per 100000 women years and the overall fall in age-adjusted incidence of cervical carcinoma was commensurate with that of England and Wales. The majority (59%) of adenocarcinomas were seen in women aged less than 50, supporting the concept of a higher risk in young women. Screen-detected carcinomas accounted for 50% of adenocarcinomas and 41% of squamous cell carcinomas in women aged 20-64 (the difference was not significant). There were more screen-detected adenocarcinomas of less than 3 mm depth of invasion and 7 mm lateral extension during the third period of the study (1991-1993). The results are consistent with reports of an increased risk of cervical cancer in women born since 1940, and lesser effectiveness of screening in preventing adenocarcinoma compared with squamous cell carcinoma. High prevalence of early screen-detected carcinomas may have been a factor in recent reports of increased incidence of adenocarcinoma.     

Characterization of a cell line (SW756) derived from a human squamous carcinoma of the uterine cervix

Summary An established cell line, SW756, derived from a primary squamous carcinoma of the uterine cervix is described by its morphology, ultrastructure, karyotype, genetic signature analysis, HLA typing, and tumorigenesis in the nude mouse. Cultured cells obtained from the SW756 derived nude mouse tumor also were studied for chromosome and isozyme markers. The original tumor was poorly differentiated carcinoma with minimal keratinization and is compared with that occurring in the nude mouse after the cultured cells were inoculated. The nude mouse tumor showed similar histological features, but better differentiation than the original tumor. Karyotype analysis of SW756 demonstrated a hyperdiploid stem line number and several marker chromosomes (MI-M6). No HeLa marker chromosomes were identified. The isozyme pattern for SW756 reported by others has been confirmed. The unique chromosome and isozyme features have been identified repeatedly in the cultured cells and, most importantly, in the post nude mouse culture. We recommend SW756 as a defined human tumorigenic cell line derived from a primary squamous carcinoma of the uterine cervix. This investigation was supported in part by Public Health Research Grant CA-06294 from the National Cancer Institute, Department of Health and Human Services.     

Establishment and characterization of cell lines derived from nude mice transplanted squamous cell carcinoma of uterine cervix

Two human cell lines, KIMI-1 and -2 were established from nude mice transplanted tumor originated from a human squamous cell carcinoma of the uterine cervix. These two cell lines have different shapes, chromosome numbers and tumor markers, respectively.     

Report on a long-term trial of CYBEST Model 2 for prescreening for squamous cell carcinoma of the uterine cervix

The results of a 12 year field trial, on a large patient base, of the CYBEST Model 2, an automated screening system using an image analysis method, are summarized. The cell specimens were stained by a conventional Papanicolaou method. Individual cellular atypism was determined from the sum of the nuclear area, the N/C ratio, the mean nuclear optical density, and the nuclear roundness with an ambiguity function value of 0.4295. CYBEST's final assessment as 'suspicious' or 'normal' was statistically determined from a cumulative histogram of the cellular atypism of a maximum 300 detected cells for each cell population using the Kolmogrov-Smirnov test, and those of unsatisfactory samples were automatically classed as 'rejected', which occurred in 6% of the study. A total of 84 atypical preparations including 17 histologically proven carcinoma patients were encountered during the entire test period from 1977 to 1988, and the overall false negative rate was 1.19% (1/84). Among the results on a total of 42,988 slides during the test period of the last 9 years from 1980 to 1988, the false positives occurred at a rate of 30.7% (12,383/40,307 of non-dysplastic slides) and the false negatives at approximately 2% (1/55 of dysplastic slides). These results are compared with those of other important systems.     

Glassy cell carcinoma of the uterine cervix. Report of a case with cytohistologic and immunohistochemical study

BACKGROUND: Glassy cell carcinomas of the uterine cervix are poorly differentiated carcinomas composed of cells with a large, round to oval nucleus containing one or multiple prominent nucleoli, finely vacuolated eosinophilic to amphophilic cytoplasm and distinct cell borders. These cells occur in sheets and chords, with fibrovascular septae presenting a mixed inflammatory infiltrate. This neoplasm has a poor response to radiotherapy and a worse prognosis than the usual types of adenocarcinoma and squamous cell carcinoma. There are few reports on the cytologic and histopathologic features of this neoplasm. CASE: A 56-year-old woman presented with a large, exophytic cervical tumor. Exfoliative cytology showed clusters of cells and single cells with large, round to oval nuclei, with one or multiple nucleoli and moderate to large, finely granulated cytoplasm with distinct cell borders. The background of the smears had a polymorphous inflammatory infiltrate, necrotic debris and proteinaceous material. A high mitotic rate was observed, as were rare bizarre and atypical multinucleated cells. There was no evidence of koilocytes. These findings were highly suggestive of glassy cell carcinoma and were confirmed by the histologic and immunocytochemical findings, with positivity for cytokeratin (MNF116), vimentin and carcinoembryonic antigen and negativity for HMB-45. CONCLUSION: Glassy cell carcinoma of the cervix presents a cytologic picture that can be highly suggestive of the diagnosis in typical cases; however, in difficult cases ancillary techniques, such as immunocytochemistry, as well as histologic findings might confirm the diagnosis.     

Neuroendocrine small cell carcinoma of the cervix associated with endocervical adenocarcinoma: a case report

BACKGROUND: Small-cell carcinoma (SCC) of the cervix is an uncommon member of the neuroendocrine group of cervical carcinomas that is frequently intermixed with a non-SCC component in the form of an adenocarcinoma (ADC) or squamous carcinoma. CASE: Colposcopy revealed a cervical mass in a 41-year-old woman and a Pap smear the presence of some tumor cells from SCC, which was confirmed by subsequent biopsy. The patient received 3 cycles of chemotherapy and then underwent major surgery. The cervical samples showed areas of endocervical ADC adjacent to and intermixed with the SCC. Reviewing the Pap smear, a previously missed malignancy was recognized. On subsequent molecular investigation to assess clonality by microsatellite analysis, the presence of HR-HPV DNA18 on real-time polymerase chain reaction, p16(INK4a) fluorescence in situ hybridization status and the corresponding immunohistochemical expression supported the hypothesis that the two components of the tumor shared the same cell origin. CONCLUSION: SCC of the cervix is a rare but distinct HR-HPV-18-related cervical carcinoma often intermixed with a clonally related non-small cell component consisting of an ADC or squamous carcinoma. The presence of SCC tumor cells in a cervical smear should prompt a search for malignant glandular or squamous tumor cells.     

The expression of HPV-16 E5 protein in squamous neoplastic changes in the uterine cervix

To investigate the expression of human papillomavirus type 16 (HPV-16) E5 protein in squamous neoplastic changes in the uterine cervix, the specific E5 antibody was generated and used to identify the expression of E5 protein in 40 cases of HPV-16-positive tissues and 5 previously identified HPV-negative normal cervical tissues. The results revealed that E5 protein was primarily expressed in the lower third of the epithelium in low-grade squamous intraepithelial lesions (SILs) and throughout the whole epithelium in high-grade SILs. In invasive squamous carcinoma, 60% of HPV-16-infected cancers which contained the episomal viral genome had the E5 gene, and could express E5 protein which was located throughout the whole epithelium. Previously, we documented the expression of type I growth factor receptors [ERBB1/EGFR (epidermal growth factor receptor), ERBB2, ERBB3 and ERBB4] in the full range of cervical neoplasias by immunohistochemistry assay. Hence, in this study, we extensively analyzed the correlation between the expression of E5 protein and the expression of type I growth factor receptors. Among 40 HPV-16- infected cervical neoplasias, we found that the expression of E5 protein was significantly correlated with either the expression of the ERBB1 or the ERBB4 receptor.     

Immunomorphological studies of the antigen associated with squamous cell cancer of the human cervix uteri]

The existence of the antigen associated with human cervical squamous cell cancer in normal and pathologically changed cervical epithelium was studied. Immunocytochemical and immunohistochemical methods were used. It is shown that the levels of the antigen increase significantly as the severity of dysplastic changes in epithelial stratum grows and tumor invasive growth begins. The data obtained indicate that the above tumor-associated marker can be useful in the follow-up for prognosticating a course of cervical cancer and dysplasia.     

Cytokeratin expression in squamous metaplasia of the human uterine cervix

The expression of cytokeratin polypeptides in squamous metaplasia of the human uterine cervix was investigated by immunocytochemical labeling with polypeptide-specific antibodies against cytokeratins. Immunofluorescence microscopic examination of cervical tissues using various monoclonal antibodies indicated that squamous cervical metaplasia expresses a unique set of cytokeratin polypeptides, this being distinctively different from that expressed by all of the normal epithelial elements of the exo- and endocervix. The development of metaplastic foci was accompanied by the expression of cytokeratin polypeptide no. 13, which is commonly detected in stratified epithelia, and by a reduction in the level of polypeptide no. 18, which is typical of simple epithelia. The 40-kilodalton cytokeratin (no. 19) described by Moll et al., which is abundant in the columnar and reserve cells of the endocervix, was found throughout the metaplastic lesions. Only in 'well-differentiated' metaplasias did we detect polarity of cytokeratin expression reminiscent of the staining patterns in the exocervix. This was manifested by the exclusive labeling of the basal cell layer(s) with antibodies KB 8.37 and KM 4.62, which stain the basal cells of the exocervix. Furthermore, a comparison of cervical metaplasia with squamous areas occurring within endometrial adenocarcinomas pointed to a close similarity in the cytokeratin expression of the two. We discuss the use of cytokeratins as specific markers of squamous differentiation, the relationships between squamous metaplasia and cervical neoplasia, and the involvement of reserve cells in the metaplastic process.     

3-D analysis of the invasion front in squamous cell carcinoma of the uterine cervix: histopathologic evidence for collective invasion per continuitatem

OBJECTIVE: To investigate spatial tumor invasion using ex vivo specimens and pursue a new morphometric approach for a quantitative assessment of the invasion front. STUDY DESIGN: Based on histologic serial sections with up to 500 slices stained with hematoxylin-eosin, volumes of interest of the tumor invasion front were 3-D reconstructed for 13 specimens from patients with squamous cell carcinoma (SCC) of the uterine cervix. Starting from very sensitive automatic tumor segmentation, 404 presumptive loci of isolated tumor islets were detected within the reconstructed volume data sets. These loci were microscopically inspected on the slides utilizing the volume date set's coordinates. RESULTS: A single detached tumor cell cluster within the stroma could be verified and, additionally, 4 tumor emboli within lymph vessels. The main cause of all other suspect islets (false positive segmentations) was peritumoral inflammatory response. Spatial invasion front quantification was done using discrete compactness (3-D C(D)). A comparison with 2-D C(D) values from single slides yielded strong correlation (correlation coefficient: r = 0.94; p < 0.001). CONCLUSION: Collective migration in SCC of the cervix mainly occurs per continuitatem. 2-D C(D) appears adequate and applicable for the morphometry of tumor invasion front phenotypes.