[1204] Differential Expression of SIRT1 and PGC1α in Ovarian Clear Cell Carcinomas vs Endometrial Carcinomas and Renal Clear Cell Carcinomas

Manisha M Mishra, Amy S Joehlin-Price, Julie A Stephens, Adrian A Suarez. Ohio State University, Columbus, OH

Background: Agonists of the fatty acid metabolism regulator PPARγ have been shown to inhibit growth of ovarian cancer cell lines. PPARγ has also been demonstrated in endometrial carcinomas (EC) as a potential therapeutic target. The deacetylase SIRT1 is required for PGC-1α coactivation of PPARγ in liver cells. However, the presence and potential roles of PPARγ regulators in gynecological cancers has not been elucidated. We sought to determine the expression of PGC-1α and SIRT1 in ovarian clear cell carcinomas (OC) and EC. Renal clear cell carcinomas (RC) were used for comparison given their morphological similarity to the ovarian tumors and known expression of PPARγ.
Design: Immunohistochemistry (IHC) using SIRT1 (Novus, 1:200) and PGC-1α (Bethyl, 1:100) polyclonal primary antibodies was performed on sections of tissue microarrays (TMA) including 375 EC, 39 OC and 28 RC. TMA's were scored by conventional light microscopy. Positive reactivity was defined as intense nuclear staining in >50% of neoplastic cells. Chi-square tests were used to compare proportions.
Results: 56% of OC were SIRT1-positive compared to only 14% and 4% of RC and EC respectively (p<0.001), see table. With the exception of three OC all SIRT1-positive tumors were negative for PGC-1α, as were most tumors overall.

SIRT1 and PGC1α Immunoreactivity
 OCRCEC
SIRT1+22/39 (56%)4/28 (14%)15/375 (4%)
PGC1α- that were SIRT1+17/20 (85%)4/4 (100%)15/15 (100%)
PGC1α+4/37 (11%)0/28 (0%)3/375 (0.8%)
SIRT1+ that were PGC1α+3/4 (75%)N/A0/3 (0%)



Conclusions: SIRT1 was detected in 56% OC, a significantly higher proportion when compared to EC (another Müllerian carcinoma) and RC (another carcinoma with clear cell morphology), p<0.001 for both. We speculate that PPARγ regulation by SIRT1 could be of significance in OC. Negative IHC for PGC-1α, may indicate other roles for SIRT1 in many OC. Alternatively, SIRT1 deacetylation of three lysine residues located within the immunogen of the PGC-1α antibody used has to be explored. The relevance of these findings is underscored by the recent development of PPARγ agonists.
Category: Gynecologic & Obstetrics

Wednesday, March 6, 2013 9:30 AM

Poster Session V # 180, Wednesday Morning

 

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