Transformation in recurrent ovarian granulosa cell tumors: Ki67 (MIB-1) and p53 immunohistochemistry demonstrates a possible molecular basis for the poor histopathologic prediction of clinical behavior

Human Pathology
M J CostaL M Roth

Abstract

Ovarian granulosa cell tumors (GCTs) behave unpredictably. Stage I patients suffer recurrences many years after treatment, and histopathologic evaluation of the primary GCT offers only a few clues. Grading, in particular, is largely ineffective. Ki67 (MIB-1) and p53 monoclonal antibodies (active on paraffin embedded tissues) provide insight into nuclear proliferation and control, respectively. In this study, the authors hypothesized that these molecular markers will help predict the clinical behavior of GCTs. Paraffin sections from 68 GCTs (arising in 56 patients: 53 primary and 15 recurrent) including 34 typical and 27 diffuse adult, and seven juvenile types were immunostained for Ki67 (MIB-1 clone; Immunotech, Westbrook, ME) and p53 (DO7 clone; Novacastra Laboratories, UK). The Ki67 proliferation index (Ki67PI = percentage immunoreactive on a count of at least 400 nuclei) ranges from 1 to 50% (mean, = 12.2%; median, 9.3%). Nineteen percent of GCTs exhibited focal p53 immunoreactivity; the number of GCTs and proportion of nuclei decorated were as follows: four, <1%; seven, 1% to 10%; and one, 20%. Ki67PI was higher in recurrent tumors (P<.001) and correlated with mitotic rate (r = .75; P<.0001). p53 staining was associated wit...Continue Reading

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