Immunohistochemical Staining for DNA Mismatch Repair Proteins in Intestinal Tract Carcinoma: How Reliable Are Biopsy Samples?
Jinru Shia, Zsofia Stadler, Martin Weiser, Michael Rentz, Laura Tang, Efsevia Vakiani, Nora Katabi, Xiaoling Xiong, Jose Guillem, David Klimstra. Memorial Sloan-Kettering Cancer Center, NY
Background: In recent years, immunohistochemistry (IHC) has emerged as an efficient tool in the detection of DNA mismatch repair (MMR) proteins in colorectal cancer (CRC). At the current time, the IHC test is mainly applied to CRC resection specimens. Detection of MMR abnormality at the biopsy stage carries obvious clinical importance as it would allow more informed decision about the extent of surgery (segmental resection versus total colectomy, prophylactic hysterectomy etc.) and, in the case of treated rectal carcinoma with no residual tumor, a means for MMR IHC. However, whether biopsy samples can be used reliably or not remains to be determined.
Design: Paired biopsy and resection specimens of adenocarcinomas of the gastrointestinal (GI) tract were analyzed for IHC staining patterns for MLH1, MSH2, MSH6 and PMS2. Abnormal staining was defined as total loss of protein in the tumor with appropriate controls. Cases with focal and weak staining, defined as staining present in <10% of the tumor with weak staining intensity, were recorded.
Results: Of a total of 70 GI tract cancers (3 from small bowel, 36 right colon, 15 left colon, and 16 ano-rectum), both biopsy and resection specimens detected the same 29 patients as having loss of staining for at least 1 MMR protein, 14 affecting MLH1/PMS2 and 15 affecting MSH2/MSH6. Focal and weak staining was most commonly seen for MLH1 stain in biopsy specimens (4/70, 6%), followed by MSH6 stain in biopsy specimens (3/70, 4%). Concordant staining patterns between biopsies and resections were reached in all 70 cases for MSH2 and PMS2, whereas discordant patterns were identified in 3 cases (3/70, 4%) for MLH1 and in 2 (2/70, 3%) for MSH6. None of the discordant patterns affected the final interpretation of whether MMR IHC was normal or abnormal in either the biopsy or the resection.
Conclusions: This study provides data suggesting that biopsy samples are as reliable as resection in the immunohistochemical detection of MMR protein abnormality in intestinal cancers. Our study also illustrates the various staining variations that can occur in both biopsies and resections. Awareness and further understanding of such staining variabilities will enhance the utility of IHC, a commonplace tool that is being increasingly used in the screening workup for Lynch syndrome.
Wednesday, March 2, 2011 9:30 AM
Poster Session V # 60, Wednesday Morning