Mullerin neoplasia of the ovaries

Abstract

In order to develop models of human ovarian cancer, attempts were made to establish a variety of neoplastic ovarian tissues as cell lines and as xenografts in nude mice. The ig_yitrg and in_yiyg phenotype of these cells was then characterised using cytogenetics, and DNA flow cytometry. A number of differentiation and tumour progression-related cell surface and cytoplasmic markers were also monitored. Cell invasive properties were studied using" two recently developed 'techniques to investigate metastatic behaviour. Preliminary efforts were made to develop monoclonal antibodies to the JoN cell line. Long-term cell and xenograft lines were successfully established from a high proportion of ovarian carcinoma patients studied, whether derived from solid tumours or malignant effusions. All cell lines grew as monolayers with variable doubling time and morphology. There were seven serous carcinomas (JN, JC, JC P/E, NW, JV, JG and LMcM), two carcinosarcomas (JoN and NF) and one clear cell carcinoma (GG) established and characterised. In the case of the JoN cell line two subpopulations separated by density—gradient centrifugation were established as cell lines and xenografts. Primary cultures (up to three months) were also established from five borderline ovarian tumours and from normal fetal and post—menopausal ovary. In general all the lines and cultures were similar morphologically to their tumours of origin, however the carcinosarcoma-derived lines showed predominantly epithelial features. Regardless of the DNA content of the original tumour, as monitored by flow cytometry, none of the lines established in culture remained diploid beyond the first 3-4 passages. The commonest cytogenetic abnormalities among the cultured cell lines were deletions of chromosome 1, followed by chromosomes 3, 4 and 7. Double minutes were frequent and a 13p duplication developed during culture of one line (JON). There was no single cytogenetic abnormality common to all lines. Epithelial membrane antigen (EMA) and keratin were commonly expressed among the established cell lines, especially in those from serous borderline tumours. Vimentin was detected in six lines, usually in conjunction with keratin. In contrast to the serous carcinoma lines, one subline of the JoN carcinosarcoma line (HDF) stained positive with desmin

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