KEY WORDSBRK
Research PaperThe BRK Tyrosine Kinase is Expressed in High-Grade Serous Carcinoma of the Ovary ABSTRACT Background: We identified the BRK tyrosine kinase in a PCR-based screen of tyrosine kinases expressed by ovarian tumors. BRK expression is restricted to normal differentiating epithelial cells and its overexpression may play a role in processes related to tumor development and growth. Its expression in normal ovary and ovarian tumors has not previously been described, and is the focus of this study.Methods: BRK expression levels were determined in 14 normal ovaries and 138 high-grade, late stage serous carcinomas of the ovary by immunohistochemical analysis, and in 19 ovarian cancer cell lines and immortalized ovarian surface epithelium by Western blot analysis. Furthermore, BRK/PTK6 gene copy number was determined in seven primary serous carcinomas by fluorescence in situ hybridization.Results: Immunohistochemical studies indicate that BRK is highly expressed in 97/138 (70%) of high-grade, serous carcinomas of the ovary, but is absent in normal ovarian surface epithelia. BRK is also expressed by 9/19 of ovarian cancer cell lines, but is undetectable in immortalized ovarian surface epithelium. Interestingly, the BRK gene has been mapped to chromosome 20q13.3, a site frequently amplified in ovarian cancers, and associated with poor prognosis. We have determined by fluorescence in situ hybridization (FISH) that BRK is specifically amplified at low levels in 6/7 primary ovarian carcinomas.Conclusions: The amplification of the BRK gene and overexpression of BRK protein in the majority of high-grade serous carcinomas and ovarian cancer cell lines suggest that BRK may play a role in the development and growth of ovarian tumors.
Glutathione-S-transferase pi (GST pi) is a multifunctional protein that acts as an enzyme, involved in the detoxification of drugs and carcinogens. It has been implicated both in drug resistance and malignant transformation of epithelium. Using an indirect immunohistochemical technique, we have evaluated cytoplasmic and nuclear staining in normal urothelium, 23 superficial bladder tumours and 26 invasive tumours. All 26 invasive tumours had been treated with platinum-based chemotherapy. Cytoplasmic staining was seen in normal urothelium and all bladder tumours. Nuclear staining was seen in 1 superficial tumour and in 13 invasive tumours. There was no association between nuclear staining and response to chemotherapy. Nuclear staining was seen in 1 area of dysplasia and in 2 of 3 areas of carcinoma in situ. GST pi expression is not a predictor of response to chemotherapy. Increased intra-nuclear expression of GST pi may be associated with progression of transitional cell carcinoma of the bladder.
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