Bcl-2: Bax and Bcl-2: Bcl-x ratios by image cytometric quantitation of immunohistochemical expression in ovarian carcinoma: correlation with prognosis

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Abstract
Bcl‐2 is a proto‐oncogene which is involved in prolonging cell survival by inhibiting programmed cell death. Bax and bcl‐x are members of the bcl‐2 family; when overexpressed, they can counteract the ability of bcl‐2 to inhibit apoptosis. This suggests a model in which the ratios of bcl‐2 to bax and bcl‐x can be used to determine response to therapy and prognosis. The expression of bcl‐2, bax and bcl‐x was studied in 50 ovarian carcinomas. The percentage of positive area immunostained (PPA) in the nucleus and cytoplasm of each ovarian carcinoma was quantitated in 15 high power fields by image cytometry. The ratios were obtained by dividing the PPA of bcl‐2 by the PPA of bax and bcl‐x. 17 of 50 ovarian carcinomas (34%) stained positively for bcl‐2, 39 for bax (78%) and 47 for bcl‐x (94%). Although there is no significant statistical correlation between expression of bcl‐2, bax or bcl‐x and grade (P = 0.15; P = 0.47; P = 0.56), stage (P = 0.71; P = 0.6; P = 0.42), and overall or disease‐free survival (P = 0.26; P = 0.55; P = 0.16), increased bcl‐2 expression was demonstrated in patients with shortened overall and disease‐free survival. Also, increased expression of bax and bcl‐x was associated with increased overall and disease‐free survival. Bcl‐2:bax and bcl‐2:bcl‐x ratios less than 1 are associated with survival advantage, although not statistically significant (P = 0.83; P = 0.93). Image cytometric measurement of bcl‐2, bax, and bcl‐x expression is feasible. There is a tendency for their expression to correlate with prognosis in ovarian carcinomas.Cytometry (Comm. Clin. Cytometry) 42:61–66, 2000