A Comparative Study of Tissue Microarray (TMA) Versus Conventional Immunohistochemistry (IHC) for Evaluation of Mismatch Repair (MMR) Systems in Colorectal Cancers (CRCs)
Sara Brownschidle, Mark Evans, Taka Ashikaga, Anita Iyer. Fletcher Allen Health Care, Burlington, VT
Background: 15–20% of CRCs show microsatellite instability (MSI), a subset associated with better outcomes, poor response to 5-FU and includes Lynch Syndrome. Whole slide (WS) IHC for MMR proteins (MLH1, MSH2, PMS2, MSH6) is popular, however TMA is a cost effective option which allows for high throughput analysis and may be a viable option as institutions adopt universal screening. Little is known about optimal sampling when constructing a TMA. We evaluated concordance rates between WS IHC and TMA and explored the effect of TMA core sites (center versus advancing edge) on concordance.
Design: MMR protein expression was analyzed in 52 unselected cases of primary CRC, first by WS IHC and then by TMA on the same block. TMA included four (1 mm) cores per case, two from the center and two from the advancing edge. Staining was graded as positive, negative (absence of tumor nuclear staining with concurrent positive labeling of surrounding normal tissue) or equivocal (indeterminate staining pattern, insufficient tumor for evaluation).
Results: Of the 52 cases, 36 (69%) stained positive for all proteins, 14 (27%) had concurrent loss of MLH1 and PMS 2 and 2 (4%) had concurrent loss of MSH2 and MSH6 by WS examination. Comparison of WS versus TMA showed an overall concordance of 96%, 98%, 96% and 98% for MLH1 (see figure with TMA on left and WS on right), MSH2, MSH6 and PMS2 respectively, with only 4 discordant cases. Features associated with discordance included weak patchy staining of MSH6 and MSH2, background lymphocytes obscuring interpretation, and inadvertent coring outside the tumor area. No improvement in staining was found between cores taken from the tumor advancing edge versus center.
Conclusions: MMR protein expression by TMA yields comparable results to that of WS IHC and thus may be feasible for diagnostic purposes in a clinical practice setting. While studies have suggested the advancing tumor margin may be more consistently immunoreactive compared to the tumor center, we found no difference in concordance between these locations. In fact, cores taken from the tumor periphery were more likely to miss the tumor and better results may be obtained from the tumor center or combining center and advancing edge.
Category: Quality Assurance
Monday, March 19, 2012 9:30 AM
Poster Session I Stowell-Orbison/Surgical Pathology/Autopsy Awards Poster Session # 310, Monday Morning