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Mismatch repair status in sporadic colorectal cancer: Immunohistochemistry and microsatellite instability analyses
Author(s) -
Yoon Yong Sik,
Yu Chang Sik,
Kim Tae Won,
Kim Jong Hoon,
Jang Se Jin,
Cho Dong Hyung,
Roh Seon Ae,
Kim Jin Cheon
Publication year - 2011
Publication title -
journal of gastroenterology and hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.214
H-Index - 130
eISSN - 1440-1746
pISSN - 0815-9319
DOI - 10.1111/j.1440-1746.2011.06784.x
Subject(s) - microsatellite instability , medicine , mlh1 , msh2 , hazard ratio , immunohistochemistry , colorectal cancer , oncology , pathology , gastroenterology , dna mismatch repair , cancer , confidence interval , microsatellite , biology , biochemistry , allele , gene
Background and Aim: The aim of the present study was to evaluate associations between mismatch repair (MMR) status and clinicopathological characteristics and prognosis using immunohistochemistry (IHC) and microsatellite instability (MSI) analyses in a prospective cohort of a large number of accumulated samples. Methods: Tumor tissue samples obtained during curative surgery ( n = 2028) were analyzed using both MLH1/MSH2 IHC and MSI assays. Clinicopathological parameters and survival outcomes were compared according to IHC and MSI results. The median follow‐up period was 43 months (range: 1–85 months). Results: IHC identified 207 tumor samples (10.2%) with a loss of either MLH1 or MSH2 expression. The MSI analysis identified 203 tumor samples (10%) with high‐frequency MSI (MSI‐H). Patients with MMR defects were younger, and had tumors characterized by right‐colon predilection; large‐size, infrequent lymph node metastasis; poorly‐differentiated or mucinous histology, and synchronous adenomas ( P < 0.001–0.008). Patients with MSI‐H status had higher 4‐year disease‐free survival rates than patients with microsatellite stable status (90.8% vs 80.6%, P = 0.001). A multivariate analysis showed that MSI‐H status was a good prognostic factor for recurrence (hazard ratio: 0.48, 95% confidence interval: 0.30–0.83, P = 0.007). Conclusions: Patients with MMR defects had distinct clinicopathological characteristics, including a lower risk of recurrence. IHC and MSI analyses provided complementary information regarding specific clinicopathological parameters and prognosis.