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An Immunohistochemical Comparison of P53 and Bcl-2 as Apoptotic and MIB1 as Proliferative Markers in Low-Grade and High-Grade Ovarian Serous Carcinomas

Background: Traditionally, ovarian serous carcinomas (OSCs) have been graded using a 3-tiered system, as well differentiated, moderately differentiated, and poorly differentiated. Recently, a 2-tiered system has been proposed depending on the nuclear atypia and mitotic count. The dualistic pathway of ovarian serous carcinogenesis with accumulating molecular genetic evidence forms the basis for this grading system. Objective: To investigate the expression of apoptotic proteins, p53 and bcl-2, and MIB1 index in low-grade and high-grade OSCs. Methods: Eighteen cases of low-grade OSCs and 28 cases of high-grade OSCs were stained immunohistochemically with antibodies against p53, bcl-2, and MIB1. For p53 and bcl-2, staining was evaluated on a semiquantitative scale depending on the number of cells showing positivity. For MIB1, the percentage of positive nuclei was calculated. Results: Of 28 cases of high-grade OSCs, 15 (53.6%) showed 5+ staining with p53 compared with 3 (16.7%) of 18 cases of low-grade OSCs. Of 28 cases of high-grade OSCs, 10 (35.7%) showed 5+ staining with bcl-2 compared with 2 (11.1%) of 18 cases of low-grade OSCs. The mean MIB1 index was 42.1% in high-grade OSCs (range, 10%-90%) in contrast to the 19.4% (range, 10%-40%) in low-grade OSCs. The differences in apoptotic protein expression and proliferative index between the low-grade and high-grade OSCs were statistically significant (P < 0.05). Conclusions: The expression of apoptotic markers is higher in high-grade OSCs, which also have a higher proliferative activity compared with those in low-grade OSCs, which supports the dualistic pathway of ovarian serous carcinogenesis.