Heterogeneous Staining for Mismatch Repair Proteins during Population-Based Prescreening for Hereditary Nonpolyposis Colorectal Cancer

Abstract

The aim of this study was to determine the frequency of microsatellite instability (MSI ؉ )

SDHB/SDHA immunohistochemistry in pheochromocytomas and paragangliomas: a multicenter interobserver variation analysis using virtual microscopy: a Multinational Study of the European Network for the Study of Adrenal Tumors (ENS@T)

“…37 Along the same lines, heterogeneous expression patterns have been reported both with MMR protein immunohistochemistry in Lynch syndrome and PTEN immunohistochemistry in Cowden syndrome. 49,69,70 The biologic nature of heterogeneous tumors in these genetic contexts is currently unknown. 37,49,69,70 Because of potential misinterpretation of heterogeneous patterns for SDHB and/or SDHA protein loss, SDH genetic testing is recommended when confronted with such cases.…”

“…49,69,70 The biologic nature of heterogeneous tumors in these genetic contexts is currently unknown. 37,49,69,70 Because of potential misinterpretation of heterogeneous patterns for SDHB and/or SDHA protein loss, SDH genetic testing is recommended when confronted with such cases. In addition to a comprehensive next-generation sequencing-based strategy for the analysis of multiple pheochromocytoma/paraganglioma susceptibility genes, [43][44][45] several algorithms have been proposed as a targeted approach to genetic testing in clinical practice.…”

PCR versus Immunohistochemistry for Microsatellite Instability

“…In the paper by Watson et al, 1 the authors' conclusion that PCR for microsatellite instability is superior to immunohistochemistry (IHC) for mismatch repair proteins for the detection of hereditary nonpolyposis colorectal cancer/Lynch syndrome is not supported by their data. In the only direct comparison of the techniques (Table 3 of the paper), both techniques successfully identified the same 19 cases as mismatch repair deficient, the same 187 cases as mismatch repair proficient, and both techniques each missed one mismatch repairdeficient tumor.…”

“…Samowitz and Broaddus for their correspondence regarding our paper in which we reported heterogeneous staining for the expression of mismatch repair (MMR) proteins. 1 Although the results from immunohistochemistry (IHC) and microsatellite instability (MSI) testing showed excellent concordance (Table 3), it should be borne in mind that MSI status was compared against the IHC criterion of complete loss of MMR expression. As stated in our paper, our experience with IHC was that a high proportion (75%) of microsatellite stable (MSIϪ) cases showed heterogeneous patterns of MMR protein loss.…”

Multiplex SNaPshot Genotyping for Detecting Loss of Heterozygosity in the Mismatch-Repair Genes MLH1 and MSH2 in Microsatellite-Unstable Tumors

“…Therefore, by revealing the presence of MLH1 or MSH2 LOH in an MSI-positive tumor, our method could eliminate further need for IHC analysis and appreciably lower the cost of prescreening in a nonnegligible percentage of cases. This approach could be especially useful when technical difficulties arise in the execution and/or interpretation of IHC assays (32)(33)(34)(35)(36)(37). The final results of IHC analyses are influenced by several factors, including those related to preparing the FFPE sample (type of fixative, fixation times, temperatures reached during the embedding procedure).…”