Immunophenotypes and gene mutations in colorectal precancerous lesions and adenocarcinoma.
- Author:
Wen-ting HUANG
1
;
Tian QIU
1
;
Yun LING
1
;
Su-sheng SHI
1
;
Lei GUO
1
;
Bo ZHENG
1
;
Ning LÜ
1
;
Jian-ming YING
2
Author Information
- Publication Type:Journal Article
- MeSH: Adaptor Proteins, Signal Transducing; metabolism; Adenocarcinoma; genetics; metabolism; Adenoma; genetics; metabolism; Aged; Class I Phosphatidylinositol 3-Kinases; Colonic Polyps; genetics; metabolism; Colorectal Neoplasms; genetics; metabolism; DNA Mismatch Repair; DNA Modification Methylases; metabolism; DNA Repair Enzymes; metabolism; DNA, Neoplasm; metabolism; DNA-Binding Proteins; metabolism; Female; Humans; Hyperplasia; Immunophenotyping; Male; Middle Aged; MutL Protein Homolog 1; MutS Homolog 2 Protein; metabolism; Nuclear Proteins; metabolism; Phosphatidylinositol 3-Kinases; genetics; Point Mutation; Precancerous Conditions; genetics; metabolism; Proto-Oncogene Proteins; genetics; Proto-Oncogene Proteins B-raf; genetics; Proto-Oncogene Proteins p21(ras); Sequence Analysis, DNA; Tumor Suppressor Proteins; metabolism; ras Proteins; genetics
- From: Chinese Journal of Pathology 2013;42(10):655-659
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVETo analyze immunophenotypes and gene mutations of colorectal precancerous lesions and adenocarcinoma, and to compare the difference of carcinogenetic mechanisms between the two precancerous lesions.
METHODSFifty-three cases of colorectal serrated lesions including 30 hyperplastic polyps, 20 sessile serrated adenomas (SSA) and 3 mixed polyps were collected from January 2006 to June 2012.Forty-five cases of traditional adenomas and 50 cases of colorectal adenocarcinomas were also recruited. Thirty hyperplastic polyps, 20 cases of SSA, 3 mixed polyps and 45 traditional adenomas were investigated by immunohistochemistry for the expression of DNA mismatch repair (MMR) proteins (MLH1, MSH2 and MSH6) and DNA methyltransferase MGMT. Mutations of KRAS, BRAF and PIK3CA genes in 10 cases of SSAs, 10 traditional adenomas, 1 mixed polyps and 50 colorectal adenocarcinomas were analyzed by PCR followed by direct Sanger sequencing.
RESULTS(1) Only 3 cases of hyperplastic polyps lost MLH1 expression, and none of SSAs or traditional adenomas showed loss of MLH1. The negative expression rates of MSH2, MSH6 and MGMT in hyperplastic polyps and SSA were significantly higher than those of traditional adenomas. (2) KRAS mutation was found in 5/10 cases of SSAs, 5/10 traditional adenomas and 1/1 mixed polyps. (3) Colorectal adenocarcinomas harbored the mutations of KRAS (48%, 24/50), BRAF (6%, 3/50) and PIK3CA (4%, 2/50).
CONCLUSIONSImmunophenotypic and gene mutation profiles are different between colorectal serrated lesion and traditional adenoma. Alterations of MMR and MGMT expression play important roles in the pathogenesis of "serrated neoplasm". KRAS mutation is a significant genetic change in the early phase of colorectal carcinogenesis.
