Stathmin 1 Is a Potential Novel Oncogene in Malignant Melanoma
Ami Wang, Jiamin Chen, Marie S Abi Daoud, Harriet E Feilotter, Victor A Tron. Queen's University, Kingston, ON, Canada
Background: Stathmin-1 (STMN1) is thought to function by reorganizing microtubule in the cytoskeleton. In a recent high throughput study from our laboratory, we identified miR-193b as a potential tumor suppressor in melanoma (1). In that study, we reported that STMN1 was a potential target of miR-193b. Recently, experimental work in our laboratory has validated STMN1 as a direct target of miR-193b. We found that STMN1 up-regulates cell proliferation and migration in vitro. Using a small tissue microarray (TMA), we demonstrated that STMN1 was up-regulated in malignant melanoma relative to benign nevi. In this study, we examined STMN1 expression in a larger, independent cohort, and assessed its role as a potential oncogene.
Design: From our archives, we assembled a cohort of 30 common benign nevi, 71 primary melanoma and 45 metastatic melanoma tissue samples, including 21 matched primary and metastatic melanoma tissues. From each case, two 6 mm cores were taken to construct the TMA. Subsequently, immunohistochemistry was performed using antibodies against STMN1. Staining intensity was quantified digitally using the Aperio Imagescope.
Results: The mean STMN1 staining intensity (total number of positive pixels/total number of pixels) in benign nevi, primary and metastatic melanoma was found to be 0.4%, 11.4% and 18.4% respectively, showing a statistically significant difference between benign nevi and primary melanoma (P < 0.001), as well as between benign nevi and metastatic melanoma (P < 0.001). The difference between primary and metastatic melanoma did not reach significance (P=0.068). In a sub-analysis using only the matched primary and metastatic melanoma pairs, the mean percentage positivity for primary and metastatic melanoma was 10.3% and 18.1%, respectively (P = 0.10).
Conclusions: In this study, we validate higher expression of STMN1 in melanoma relative to benign nevi, supporting the notion that STMN1 may function as an oncoprotein. Our data suggest that STMN1 may be involved in the early stages of melanoma pathogenesis since it is up-regulated in primary melanoma. Additional studies will be carried out to determine potential prognostic significance of STMN1 expression levels, and to provide more direct evidence for a role for STMN1 in melanoma pathogenesis using animal models.
1 Chen J, Feilotter HE, Paré GC, Zhang X, Pemberton JG, Garady C, Lai D, Yang X, Tron VA. MicroRNA-193b represses cell proliferation and regulates cyclin D1 in melanoma. Am J Pathol. 2010 May;176 (5):2520-9.
Monday, March 19, 2012 9:30 AM
Poster Session I Stowell-Orbison/Surgical Pathology/Autopsy Awards Poster Session # 79, Monday Morning