Androgen Receptor Coactivator p44/Mep50 in Ovarian Cancer
LY Pan, JJ Wei, RR Patwa, M Ligr, S Jain, XY Zou, G Daniels, YR Li, RL Xu, W Sun, ZX Wang, P Lee, F Chen. New York University, New York, NY; NY Harbor, New York, NY; MD Anderson, Houston, TX
Background: Hormones, including estrogen and progesterone, and their receptors play an important role in the development and progression of ovarian carcinoma. Androgens and androgen receptors have also been implicated. The methylosome complex, with a p44 as a subunit, has lately been characterized as an androgen receptor coactivator, which enhances androgen receptor- and estrogen receptor-mediated transcriptional activation in a ligand-dependent manner. We previously examined the expression and function of p44 in prostate, testis and breast cancers and observed organ specific p44 subcellular location and function. In this report, we examined the expression of p44 in ovarian cancer.
Design: Immunohistochemistry was performed using a p44/Mep50 antibody on a tissue microarray of ovarian cancer (n = 56): 14 mucinous (MUC), 13 clear cell (CCC), 10 endometrioid (EMC), 8 serous borderline (SBT), and 11 fallopian tube high grade serious carcinoma (FT). The levels of p44 cytoplasmic and nuclear expression were scored semi-quantitatively: 0 as negative, 1+ as faint, 2+ as weak, 3+ as moderate and 4+ as strong expression. The percentage of cells was given: 1 as 0-10%, 2 as 10-50%, 3 as 50-75% and 4 as 75-100%. Statistical analyses were performed by t-test.
Results: All 5 types of ovarian carcinoma revealed both nuclear and cytoplasmic p44 at various levels. For cytoplasmic staining, EMC showed the strongest intensity (2.85 ± 0.06), while MUC showed the weakest of both intensity (1.35 ± 0.06) and percentage (3.5 ± 0.09). In contrast to normal ovarian tissue, all types of tumors showed positive nuclear staining in greater than 50% of cells. Again, MUC showed the weakest staining, in intensity (2.04 ± 0.04) and percentage (3.13 ± 0.17). SBT showed the strongest intensity, (3.0 ± 0). FT and CCC tumors showed the next highest intensity, (respectively 2.52 ± 0.16 and 2.5 ± 0.13). This nuclear p44 expression is consistent with its growth stimulatory effects.
Conclusions: The expression of p44 shows strong cytoplasmic expression in morphologically normal ovarian surface epithelium and fallopian tubes, while cytoplasmic and nuclear p44 localization is observed in invasive ovarian carcinoma. Since MUC has lower ER cytoplasmic p44 expression, these findings suggest that nuclear p44 may play a role as an estrogen receptor mediator in the tumorigenesis of serous and clear cell ovarian carcinoma.
Category: Gynecologic & Obstetrics
Wednesday, March 24, 2010 1:00 PM
Poster Session VI # 160, Wednesday Afternoon