[999] Dedifferentiated Carcinoma of the Endometrium and the Ovary: A Molecular Study of 8 Cases.

Ainara Azueta, Sonia Gatius, Ana Velasco, Maria Santacana, Judit Pallares, Blaise Clarke, Esther Oliva, Xavier Matias-Guiu. Hospital Universitari Arnau de Vilanova, University of Lleida, IRB Lleida, Spain; Massachusetts General Hospital, Boston; Toronto General Hospital, Canada

Background: Dedifferentiated carcinoma (DC) is an uncommon neoplasm accounting for 1-9% of all endometrial carcinomas (EC) being even more rare in the ovary. It is characterized by the presence of undifferentiated carcinoma (UC) juxtaposed to foci of low-grade endometrioid carcinoma (EEC). Some studies have demonstrated abnormal expression of proteins involved in DNA mismatch repair gene but the molecular features of this type of tumors have not been evaluated. Moreover, a role for p53 has been suggested in the progression from EEC to non-endometrioid (NEEC) carcinoma component, in mixed EEC-NEEC tumors.
Design: Eight DC were included (7 endometrial and 1 ovarian). Immunohistochemical study included MLH-1, MSH-2, MSH-6, PMS-2, and p53. DNA was obtained from paraffin-embedded blocks, and was subjected to microsatellite instability (MI) analysis, methylation specific PCR, and mutational analysis of p53.
Results: p53 immunostaining was positive in seven of the eight cases in the two components (strong staining in two cases, moderate in three, and low in two). Loss of MLH1/PMS-2 expression was seen in four cases (both components), while loss of MSH-2 /MSH-6 expression was seen in one (both components). In three cases, there was normal staining pattern for MLH-1, MSH-2, MSH-6, and PMS-2. MI was seen in all five cases with abnormal staining of mismatch repair genes. MLH-1 promoter hypermethylation was detected in all four cases exhibiting MI and decreased MLH-1 expression. One p53 mutation (T155P, exon 5) was found in one tumor in both components.
Conclusions: DC frequently exhibits microsatellite instability and loss of proteins involved in mismatch repair. Moreover, there is frequent p53 positivity, but with only occasional p53 mutations. The results suggest that alterations in mismatch repair genes and p53 may be associated with development of DC.
Category: Gynecologic & Obstetrics

Wednesday, March 2, 2011 1:00 PM

Poster Session VI # 166, Wednesday Afternoon

 

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