Do Microsatellite Instability Markers Have a Role in Differentiation of B Cell Neoplasms
B Khandpur, R Bhat, JS Hou. Drexel University College of Medicine, Philadelphia, PA
Background: The aim of the present study was to understand the roles of DNA mismatch repair defects and microsatellite instability (MSI) markers, p53 and Ki-67 markers in development of B cell lymphomas.
Design: 28 patients with diffuse large B cell lymphoma (DLBCL) and follicular lymphoma (FL) were identified (DUCOM surgical pathology, 2004-2009). Reactive lymph nodes were used as control. A tissue micro array was prepared from paraffin embedded tissue blocks (18 DLBCL, 10 FL, 9 reactive) using a 15 gauge bone marrow puncture needle with adhesive tape embedding system; with 2 cores/case. Immunoperoxidase stains for CD10, CD20, p53, Ki67, MLH1, MSH2, and MSH6 were performed. Microsatellite instability (MSI) markers were graded as absent/reduced or present, with absence of anyone marker classified as MSI present. Microarray slides were analyzed with ScanScope XT (Aperio, Vista, CA). SPSS software was used for statistical analysis.
Results: Average age of patients at diagnosis was 56.9 years (range 26-84 yrs). Loss of microsatellite instability markers was evaluated between FL and DLBCL cases and also lymphomas vs benign cases. MLH1 was absent in 5/28 patients (2 DLBCL and 3 FL), MSH2 in 2/10 patients with FL lymphomas (p<.05) and MSH6 in 3/18 patients of DLBCL. None of the cases of DLBCL expressed loss of MSH2. 7 patients (4 DLBCL and 3 FL) were hence recorded as positive for MSI. Signficant differences were identified in the expression of p53 between FL (mean 6, SD 2.9, p<.001)and DLBCL (mean 25, SD 16.8) similar to Ki-67 expression between FL (mean 22, SD 9.7, p<.05) and DLBCL (mean 71, SD 19.7). Non parametric correlations were performed and significant correlation was identified between p53 and MLH1 and MSH2 and between Ki67 and MSH2.
Conclusions: Even though a small percentage of B cell lymphomas express loss of microsatellite instability markers by immunohistochemistry, we document for the first time a significant association between FL and loss of MSH2 and DLBCL and loss of MSH6 markers. Additional studies will be conducted to recognize the differences. Significant diagnostic difference was observed in p53 and Ki-67 immunostains between FL and DLBCL. Significance of correlation between p53 and MLH1 and MSH2 as well as Ki-67 and MSH2 remains uncertain.
Monday, March 22, 2010 9:30 AM
Poster Session I Stowell-Orbison/Surgical Pathology/Autopsy Awards Poster Session # 184, Monday Morning