Expression of p53, c-erbB-2, Ki-67, and CD34 in granulosa cell tumor of the ovary

Abstract

The purpose of this study is to investigate the expression of p53, c-erbB-2, Ki-67, and angiogenic activity and their correlation with the clinicopathologic characteristics in a series of granulosa cell tumors of the ovary (GCTO). Eighteen GCTO cases assisted at the Department of Obstetrics and Gynecology, School of Medical Science, UNICAMP, after diagnostic confirmation by three pathologists, were submitted to immunohistochemistry for assessment of p53, c-erbB-2, Ki-67, and CD34 expressions. The mean tumor size was 13 cm (range: 4–30 cm). Six (33%) cases presented with extraovarian disease. Thirteen (72%) cases presented some solid diffuse or sarcomatoid pattern and six (33%) moderate or strong atypia. Fourteen cases presented ≤2 mitoses/10 HPF. Thirteen cases were focally positive for Ki-67. The mean Ki-67 proliferative index was 1.0%. One case presented positive expression for mutant p53 but all cases were negative for c-erbB-2 expression. The mean microvascular density was 28.9/mm2 (range: 0–50). No significant correlations could be established between the biologic markers and clinicopathologic variables. GCTO showed a markedly low rate of immunohistochemical staining for p53 or c-erbB-2 overexpression/amplification, as well as low proliferative and angiogenic activities. Further studies are urgently needed to elaborate the factors responsible for the highly unpredictable clinical course of GCTO.

Prognostic factors in ovarian adult granulosa cell tumour

“…We reiterate the point that pathological review is important in such studies since some of the mimics of AGCT, such as OSCCHT, are typically diffusely p53 positive 34. Other authors have reported no prognostic significance of p53 immunohistochemical staining 5 23 24 27 28. These variations may be partly explained by differing immunohistochemical methods and scoring criteria, particularly what constitutes p53 overexpression.…”

“…Furthermore, there was no difference in proliferation between stage I and higher stage tumours. These findings are supported by some studies,5 7 9 11 20 21 24 – 26 but are contradicted by others, that have found that a high mitotic count imparts a worse prognosis, with various cut-offs of >3 to >10 mitotic figures per 10 high-power fields 6 10 13 15 22 23 27 – 29. Some studies have found elevated Ki-67 labelling indices to adversely affect prognosis 16 28 30.…”

Prognostic value of mitotic counts and Ki-67 immunoreactivity in adult-type granulosa cell tumour of the ovary

“…Therefore it is not surprising that some reports have failed to show a correlation between mitotic activity and prognosis in patients with GCT,16 – 23 and even those studies reporting such a correlation do not agree on the cut-off value for poor outcomes. More recent immunohistochemical investigations evaluating the expression of proliferation-associated markers such as proliferating cell nuclear antigen and Ki-67/MIB-1 have also failed to show consistent results 8 10 16 17 19 22 – 25…”

Characteristics of recurrence in adult-type granulosa cell tumor

“…Several studies have proposed that the mitotic index of GCT is associated with tumor recurrence despite the different cutoff points of the mitotic index (7,13,16) . Meanwhile, other molecular markers do not seem to have a prognostic significance, even though angiogenic factors such as proliferating cell nuclear antigen (PCNA) and Ki-67, p-53 and abnormal tumor karyotypes have been studied for the prediction of survival (17,18) .…”