Protein kinase C isoform expression in ovarian carcinoma correlates with indicators of poor prognosis.
In this study expression of protein kinase C alpha (PKCalpha), delta (PKCdelta) and iota (PKCiota) was determined immunohistochemically in formalin-fixed paraffin-embedded tissue specimen of ovarian cystadenomas (n=7), borderline tumours of the ovary (n=8), primary (n=54) and recurrent invasive ovarian carcinomas (n=13). The expression was correlated with clinicopathological parameters and patient survival. In addition, expression of PKCiota was assessed in 3 ovarian carcinoma cell lines (OVCAR-3, SKOV-3, OAW-42) and in one human ovarian surface epithelium (HOSE) cell line. We found expression of PKCalpha in 71.4% of cystadenomas, 50% of borderline tumours, 53.7% of primary and 38.5% of recurrent ovarian carcinomas. PKCdelta was not expressed in epithelium of adenomas, borderline tumours, primary and recurrent ovarian carcinomas. PKCiota was expressed in 51.9% of primary and 46.2% of recurrent ovarian carcinomas but not in cystadenomas and borderline tumours of the ovary. Consistent with these findings ovarian carcinoma cell lines showed strong expression of PKCiota whereas HOSE cells did not. Correlation of PKCalpha and PKCiota expression and clinicopathological features revealed a significant negative correlation of PKCalpha with histopathological grading and a significant positive correlation of PKCiota with histopathological grading and FIGO stage as well as a borderline significant positive correlation with proliferation index. Univariate survival analysis showed that amongst other yet known prognostic parameters (FIGO stage, histopathological grading, proliferation index) PKCiota expression in primary ovarian carcinomas correlated significantly (p=0.024) with a reduced median survival time, but was not an independent prognostic factor. The findings of this study, together with data from functional studies by other groups suggest that alteration of PKC isoform expression may be involved in progression of ovarian carcinomas.
Weichert
Wilko
W
Institute of Pathology, Charité Hospital, Schumannstrasse 20/21, 10117 Berlin, Germany. weichert@charite.de
Gekeler
Volker
V
Denkert
Carsten
C
Dietel
Manfred
M
Hauptmann
Steffen
S
D002277:Carcinoma / Q000175:diagnosis / Q000201:enzymology; D002460:Cell Line; D045744:Cell Line, Tumor; D018450:Disease Progression; D004847:Epithelial Cells / Q000378:metabolism; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007527:Isoenzymes / Q000096:biosynthesis*; D008856:Microscopy, Fluorescence; D010051:Ovarian Neoplasms / Q000175:diagnosis / Q000201:enzymology*; D010053:Ovary / Q000378:metabolism; D011379:Prognosis; D020033:Protein Isoforms; D011493:Protein Kinase C / Q000096:biosynthesis* / Q000737:chemistry*; D051571:Protein Kinase C-alpha; D051745:Protein Kinase C-delta; D013997:Time Factors; D000099293:Protein Kinase C-lambda
D007527:Isoenzymes; D020033:Protein Isoforms; D011493:Protein Kinase C; D051571:Protein Kinase C-alpha; D051745:Protein Kinase C-delta; D000099293:Protein Kinase C-lambda; C496628:PRKCA protein, human; C497258:PRKCD protein, human