Changes in expression of differentiation markers between normal ovarian cells and derived tumors.

The marker profile of 18 samples of normal human ovarian tissues and 138 samples of their derived tumors was established using 51 monoclonal antibodies directed against intermediate filaments, ovarian carcinoma-specific antigens, general tumor-associated antigens and MHC-I/II antigens. Our data show that vimentin and keratins 7, 8, 18, and 19 were found in both epithelial and some nonepithelial ovarian tumors. Several tumor samples contained additional keratins 4, 10, 13, and 14, as well as desmin. BW 495/36 and to a lesser extent HMFG-2 were usually found in all ovarian tumors that contained simple epithelial keratins, except the absence of HMFG-2 in gonadal tumors as well as in dysgerminomas. In contrast to the keratin antibodies, these two panepithelial antibodies were negative in normal mesothelial cells and granulosa cells of the ovarian follicles. In general, the marker TAG-72 appeared useful for its discrimination between positively stained mucinous adenomas, the ovarian carcinomas as well as germ cell tumors, and the negatively stained gonadal tumors, serous adenomas, and cystomas. OV632 appeared useful in the distinction between negatively stained serous adenomas and positively stained serous carcinomas. In contrast, the monoclonal antibodies OC 125, OV-TL 3, OV-TL 16, and MOv 18 can be considered as pan-ovarian carcinoma markers, however without the discriminative capability as seen for OV632. These ovarian carcinoma-associated antigens were hardly found expressed in gonadal and germ cell tumors, except in the group of endodermal sinus tumors. HLA-I was found to be expressed in almost all nucleated cells, although loss of HLA-I expression was seen in areas of tumor cells. HLA-DR was negative in normal ovarian tissue, but heterogeneous expression was noticed in most of the epithelial tumors.

Intermediate filament proteins in spindle cell carcinoma of the larynx and tongue.

In an analysis of intermediate filament protein expression of spindle cell carcinoma, a variant of squamous cell carcinoma, occurring in larynx and tongue, vimentin positivity was found in sarcomatoid areas in 12 of 13 patients. Scattered expression of keratin was observed in sarcomatoid areas in tumours of 10 patients. However, large parts of sarcomatoid areas of such tumours were negative for keratin. Overlying dysplastic epithelium and squamous cell carcinoma components were positive for keratin. In a number of cases there was a strong indication of co-expression of keratin and vimentin in parts of cells that, on histological grounds, belong to sarcomatoid areas or to cells in the interface between carcinoma and spindle cell area. The use of keratin and vimentin type intermediate filament antibodies could be of great help for the correct classification of these tumours.

Application of antibodies to intermediate filament proteins in simple and complex tumors of the female genital tract.

Polyclonal antibodies to cytokeratins, vimentin, and desmin and monoclonal antibodies to vimentin and to individual cytokeratin polypeptides, specific for glandular epithelia (RGE 53) or kertinizing stratified squamous epithelia (RKSE 60), have been applied in gynecological tumors with simple or complex composition. In general, tumors with simple composition showed reaction patterns fitting their known epithelial or mesenchymal nature, i.e., cytokeratin positivity in epithelial tumors only, vimentin positivity in mesenchymal tumors, and expression of desmin and vimentin in muscle cell tumors. Rather frequently, coexpression of cytokeratins and vimentin was noted in endometrial adenocarcinomas. Tumors with complex composition, such as müllerian mesodermal mixed tumors (MMMTs), that may pose considerable problems in conventional histopathology revealed various reaction patterns, with either expression of only cytokeratins or coexpression of cytokeratins and vimentin in carcinomatous areas and expression of only vimentin in sarcomatous areas. However, in addition, some MMMTs contained cells that were also positive for desmin. Intermediate filament protein immunohistochemistry appeared to be helpful in establishing a diagnosis of MMMT and in characterizing the different tumor components, which may prove to be useful in the evaluation of gynecological treatment protocols.

Co-expression of glial fibrillary acidic protein- and vimentin-type intermediate filaments in human astrocytomas.

The expression of intermediate filament (IF) proteins was studied in 71 cases of malignant human astrocytoma and in 17 cases of reactive gliosis, using immunocytochemical techniques with polyclonal and monoclonal antibodies to glial fibrillary acidic protein (GFAP) and vimentin. In all cases of astrocytoma, varying in degree of malignancy from grade I to grade IV, co-expression of GFAP and vimentin was found. No change in vimentin- or GFAP-IF expression with increasing anaplasia was seen. In addition astrocytic cells in reactive gliosis showed simultaneous expression of GFAP and vimentin. The intracellular distribution of these IF proteins differed. Vimentin was found to be located in a more juxta-nuclear position, whereas GFAP immunoreactivity showed a more intense staining of the cellular processes. Astrocytes in reactive gliosis behaved more or less like neoplastic cells. However, thin cell processes of reactive astrocytes in the cortex and superficial white matter only contained GFAP immunoreactivity. Simultaneous expression of GFAP and vimentin and their proportion in malignant and reactive glial cells are discussed in the light of earlier reports on the IF content of glial cells during development and maturation, in which vimentin precedes GFAP-expression. The existence of two separate (functional) IF systems in astroglia is suggested.