[1061] Revised Histologic Criteria for Ovarian Carcinoma Cell Type Show Improved Correlation with Genotype and Protein Expression Profile.

Yevgeniy Karamurzin, Mario Leitao, Daniel Chiappetta, David Marshal, Robert Soslow. Memorial Sloan-Kettering Cancer Center, New York, NY

Background: In 2004 we reported data emphasizing the prognostic value of TP53 mutation in FIGO stage I and II ovarian carcinoma (low stage OC). However, tumor histologic subtype, grade, and substage did not correlate with prognosis in this cohort. Histologic recalibration of these tumors using criteria proposed by Gilks et al. will allow reassessment of correlations between carcinoma type, genotype and immunophenotype.
Design: The cohort comprised 91 previously identified patients with low stage OC who underwent primary surgical management at our institution from 1980 to 2000. H&E slides were reviewed and histologic type reassigned using Gilks et al. criteria. p53 and WT1 expression was evaluated using standard immunohistochemistry (IHC) techniques on a tissue microarray. p53 expression assessment has evolved between 2004 and 2010. In 2004, p53 expression profile was reported as either positive or negative. In 2010, abnormal p53 expression was scored when there was absolute loss of staining, or overexpression involving at least 50% of cells; p53 expression was considered to be within normal limits if it was focal and involved less than 50% of cells. Direct TP53 gene sequencing of the entire coding region was performed on all cases with available tissue.
Results: Tumor histologic subtype distributions, as well as correlation between tumor cell type and the other variables are outlined in Table 1.

Table 1.
Clear cell27%25%
Malignant Brenner2%1%
Mixed epithelial11%4%
Carcinoma, unclassifiable3%0%
Serous with TP53 mutation57%75%
Non-serous with TP53 mutation24%13%
Serous with aberrant p5358%87%
Non-serous with aberrant p5331%9%
TP53 mutation with aberrant p5371%83%
Wild type TP53 with aberrant p5327%9%
Serous with WT1 expression65%77%
Non-serous with WT1 expression8%2%

Conclusions: Revised histologic diagnoses correlated more closely with TP53 mutation status and p53/WT1 expression patterns. TP53 mutations almost always result in aberrant p53 expression (complete loss or overexpression). Significantly more serous OCs had TP53 mutation, abnormal p53 expression, and WT1 positivity.These results validate the criteria of Gilks et al. and indicate that meticulous histologic assessment allows accurate biologic characterization.
Category: Gynecologic & Obstetrics

Monday, February 28, 2011 11:15 AM

Platform Session: Section D, Monday Morning


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