Expression and Prognostic Value of S-100A Proteins in Stage II Colon Cancer
KT Sciandra, BJ Winn, W Cao, R Tavares, L Noble, MB Resnick. Rhode Island Hospital, The Warren Alpert Medical School of Brown University, Providence, RI
Background: S-100 proteins are a family of calcium binding proteins, which have been implicated in various intracellular and extracellular functions ranging from the control of cell-cycle progression, cell differentitaion, extracellular signaling, cell motility, signal transduction, and intercellular adhesion to invasion and metastasis. Both over and underexpression of these proteins have been reported as independent prognostic factors in certain solid tumors. In this study we evaluated the expression of the S-100A2, A4, and A9 proteins in the normal colon and in Stage II colon cancer and correlated protein expression with patient outcome.
Design: Tissue microarrays were created from 144 cases of TNM Stage II colon carcinoma from the institution's surgical pathology archive. The tissue miroarrays were immunohistochemically stained with S-100A2 (monoclonal, Sigma), S-100A4 (polyclonal, Dako) and S-100A9 (monoclonal, Abnova). The cases were scored for intensity of cytoplasmic staining and presence or absence of nuclear staining.
Results: In normal colonic mucosa S-100A2 showed moderate to strong staining in epithelial cells, with stronger staining toward the surface, and positive nuclear staining. S-100A4 and S-100A9 staining of normal colonic tissue was negative in both the cytoplasm and nucleus of the epithelial cells. In the colon carcinoma cases, cytoplasmic staining for S-100A2 was negative in 21%, weakly positive in 25% and strongly positive in 55%, with 90% showing positive nuclear staining. Cytoplasmic staining for S-100A4 was negative in 23%, weakly positive in 11% and strongly positive in 67%, with 65% showing positive nuclear staining. Cytoplasmic staining for S-100A9 was negative in 17%, weakly positive in 26% and strongly positive in 58%, with 4% showing positive nuclear staining. Strong cytoplasmic staining with S-100A2, but not with S-100A4 and S-100A9 was associated with both better survival (P=0.012) and lack of recurrence of colon cancer (P=0.0033). There was no significant association between expression of any of the S-100A proteins and tumor differentiation or lymphovascular invasion. There was also no correlation between expression of these proteins with each other on a case per case basis.
Conclusions: The S-100A4 and A9 proteins are overexpressed in neoplastic colonic epithelium. Loss of S-100A2 expression is a novel negative prognostic factor in colonic adenocarcinoma.
Tuesday, March 23, 2010 9:30 AM
Poster Session III # 119, Tuesday Morning