title: Immunohistochemistry and microsatellite instability analysis in molecular subtyping of colorectal carcinoma based on mismatch repair competency.
abstract: Mismatch repair defective (MMRd) colorectal carcinoma (CRC) is a distinct molecular phenotype of colorectal cancer, including 12% of sporadic CRC and 3% of Lynch Syndrome. In order to investigate the clinicopathological characteristics of MMRd colorectal carcinoma, and to find the most effective method for preliminary screening, 296 CRC fulfilled revised Bethesda Guideline (RB) were selected from 1450 CRCs to perform both IHC staining for MLH1, MSH2, MSH6, PMS2 and MSI analysis. Sixty-eight tumors were classified as MSI-H by MSI test. Colorectal carcinomas with MSI-H were prone to be proximal located, poorly differentiated, and relatively early staged, with infrequent metastasis to lymph node as well as to distant organs, compared with MSS ones. All of the 68 MMRd CRCs presented abnormal expression of at least one mismatch repair protein (MMRP), with 48 concurrent negative of MLH1 and PMS2, 14 concurrent negative of MSH2 and MSH6, 4 isolated negative of MSH6, 1 isolated negative of PMS2, and 1 concurrent negative of 4 MMRPs. All of the MLH1 negative tumors also showed abnormal expression of PMS2. All of the MSH2 negative cases also presented negative expression of MSH6. The sensitivity and specificity of the 2-antibody IHC test contained only PMS2 and MSH6 for screening for MMRd CRC were 100% and 98.2% respectively, exactly the same as that of the 4-antibody IHC test with all of the 4 MMRPs. The diagnostic accordance rate of the 2-antibody approach and MSI analysis was 98.6%. In conclusion, MMRd CRC has characteristic clinicopathological features different from MSS CRCs. The 2-antibody IHC approach containing MSH6 and PMS2 is the most easy and effective way to detecting MMR deficiency in CRC.
authors.affiliation: Department of Pathology, Fudan University Shanghai Cancer CenterShanghai 200032, China; Department of Oncology, Shanghai Medical College, Fudan UniversityShanghai 200032, China; Pathology Center, Shanghai General Hospital, School of Medicine, Shanghai Jiao Tong UniversityShanghai 200080, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Yuan
authors.affiliation: Department of Oncology, Shanghai Medical College, Fudan UniversityShanghai 200032, China; Breast Cancer Institute, Fudan University Shanghai Cancer CenterShanghai 200032, China.
authors.forename: Yayun
authors.initials: Y
authors.lastname: Chi
authors.affiliation: Department of Pathology, Fudan University Shanghai Cancer CenterShanghai 200032, China; Department of Oncology, Shanghai Medical College, Fudan UniversityShanghai 200032, China.
authors.forename: Weixiang
authors.initials: W
authors.lastname: Chen
authors.affiliation: Department of Pathology, Fudan University Shanghai Cancer CenterShanghai 200032, China; Department of Oncology, Shanghai Medical College, Fudan UniversityShanghai 200032, China.
authors.forename: Xiaochen
authors.initials: X
authors.lastname: Chen
authors.affiliation: Department of Pathology, Fudan University Shanghai Cancer CenterShanghai 200032, China; Department of Oncology, Shanghai Medical College, Fudan UniversityShanghai 200032, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Wei
authors.affiliation: Department of Pathology, Fudan University Shanghai Cancer CenterShanghai 200032, China; Department of Oncology, Shanghai Medical College, Fudan UniversityShanghai 200032, China.
authors.forename: Weiqi
authors.initials: W
authors.lastname: Sheng
authors.affiliation: Department of Pathology, Fudan University Shanghai Cancer CenterShanghai 200032, China; Department of Oncology, Shanghai Medical College, Fudan UniversityShanghai 200032, China.
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Zhou
authors.affiliation: Department of Pathology, Fudan University Shanghai Cancer CenterShanghai 200032, China; Department of Oncology, Shanghai Medical College, Fudan UniversityShanghai 200032, China.
authors.forename: Daren
authors.initials: D
authors.lastname: Shi
keywords: CRC; Lynch syndrome; Mismatch repair; immunohistochemistry; microsatellite instability; molecular phenotype