Connecxin 43 May Be a Potential Prognostic Biomarker for Ewing Sarcoma (EWS)/PNET
MM Bui, TL Pasha, G Acs, PJ Zhang. Moffitt Cancer Center, Tampa, FL; Hospital of the University of Pennsylvania, Philadelphia, PA
Background: Connexin (Cx) is a family of homologous proteins that are building blocks of gap junctions (GJ) that permit direct exchange of small molecules between cells. Cx is vital in regulating cell proliferation and apoptosis, and is tumor suppressor in some and oncoprotein in other for carcinomas. Little is known for their role in sarcoma. We investigated the expression of Cx43 and Cx26 in EWS/PNET and correlated with various clinicopathologic data to explore its role in the biology of this group of tumor.
Design: Tissue microarray (TMA) consisted of 36 EWS/PNET patients (pts) from 1995-2007 were evaluated with clinicopathological data including tumor location, size, surgical margins, stage, treatment and survival. 4-m TMA slides were immunohistochemically stained for Cx43 (CXN-6, 1:250, Santa Cruz) and Cx26 (rabbit polyclonal, 1:100, Zymed). Immunoreactivity was quantitatively evaluated by automated slide scanning using Aperio ScanScope XT (Vista, CA) and Image Pro Plus v6.2 (Bethesda, MD) analysising macro algorithms based on the intensity (0-3) and % of staining. A score of 0-300 is calculated for each case as the product of the intensity score and the %. The level of expression was analyzed with various clinicopathologic factors.
Results: Among 36 pts, 19 were alive and 17 dead (median follow up 410 days). Cytoplasmic Cx43 reactivity was detected in 28/36 (78%) cases (score ranged 1-160, median 62). The score of Cx43 reactivity signficantly differed between tumors from alive (median 50) and dead (median 105) pts (p=0.0036, Mann-Whitney). When tumors was divided by median into high and low Cx43 groups, 13/18 (72%) low Cx43 tumors were from alive pts while 12/18 (67%) high Cx43 tumors from deseased (p=0.04, Fisher's exact test). The survival difference in low and high Cx43 groups approached significance (median survival 2,388 vs. 701 days, p=0.0552, Log-Rank). Cytoplasmic Cx26 reactivity was detected in 2 of 36 (6%) cases. In both cases, the patients died with metastasis (lung and brain) in 341 days and 211 days, respectively.
Conclusions: EWS/PNET express cytoplasmic Cx43 frequently (78%) and Cdx26 rarely (6%). The level of Cx43 expression correlated with outcome of EWS/PNET, regardless of their stage, location, size and management. Study in a larger series is warranted to confirm its prognostic role. Our results also suggest a possible oncogenic role of Cx 43 and less likely Cx 26 in EWS/PNET. The lack of membrane reactivity suggests that these Cx likely function in a GJ independent mechanism.
Category: Bone & Soft Tissue
Monday, March 9, 2009 1:00 PM
Poster Session II # 8, Monday Afternoon