Cargando…

Distinct Clinicopathological Patterns of Mismatch Repair Status in Colorectal Cancer Stratified by KRAS Mutations

In sporadic colorectal cancer (CRC), the BRAF(V600E) mutation is associated with deficient mismatch repair (MMR) status and inversely associated with to KRAS mutations. In contrast to deficient MMR (dMMR) CRC, data on the presence of KRAS oncogenic mutations in proficient MMR (pMMR) CRC and their re...

Descripción completa

Detalles Bibliográficos
Autores principales: Li, Wenbin, Zhi, Wenxue, Zou, Shuangmei, Qiu, Tian, Ling, Yun, Shan, Ling, Shi, Susheng, Ying, Jianming
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4456280/
https://www.ncbi.nlm.nih.gov/pubmed/26042813
http://dx.doi.org/10.1371/journal.pone.0128202
_version_ 1782374820509384704
author Li, Wenbin
Zhi, Wenxue
Zou, Shuangmei
Qiu, Tian
Ling, Yun
Shan, Ling
Shi, Susheng
Ying, Jianming
author_facet Li, Wenbin
Zhi, Wenxue
Zou, Shuangmei
Qiu, Tian
Ling, Yun
Shan, Ling
Shi, Susheng
Ying, Jianming
author_sort Li, Wenbin
collection PubMed
description In sporadic colorectal cancer (CRC), the BRAF(V600E) mutation is associated with deficient mismatch repair (MMR) status and inversely associated with to KRAS mutations. In contrast to deficient MMR (dMMR) CRC, data on the presence of KRAS oncogenic mutations in proficient MMR (pMMR) CRC and their relationship with tumor progression are scarce. We therefore examined the MMR status in combination with KRAS mutations in 913 Chinese patients and correlated the findings obtained with clinical and pathological features. The MMR status was determined based on detection of MLH1, MSH2, MSH6 and PMS2 expression. KRAS mutation and dMMR status were detected in 36.9% and 7.5% of cases, respectively. Four subtypes were determined by MMR and KRAS mutation status: KRAS (+)/pMMR (34.0%), KRAS (+)/dMMR (2.9%), KRAS (-)/pMMR (58.5%) and KRAS (-)/dMMR (4.6%). A higher percentage of pMMR tumors with KRAS mutation were most likely to be female (49.0%), proximal located (45.5%), a mucinous histology (38.4%), and to have increased lymph node metastasis (60.3%), compared with pMMR tumors without BRAF(V600E) and KRAS mutations (36.0%, 29.3%, 29.4% and 50.7%, respectively; all P < 0.01). To the contrary, compared with those with KRAS(-)/dMMR tumors, patients with KRAS(+)/dMMR tumors demonstrated no statistically significant differences in gender, tumor location, pT depth of invasion, lymph node metastasis, pTNM stage, and histologic grade. This study revealed that specific epidemiologic and clinicopathologic characteristics are associated with MMR status stratified by KRAS mutation. Knowledge of MMR and KRAS mutation status may enhance molecular pathologic staging of CRC patients and metastatic progression in CRC can be estimated based on the combination of these biomarkers.
format Online
Article
Text
id pubmed-4456280
institution National Center for Biotechnology Information
language English
publishDate 2015
publisher Public Library of Science
record_format MEDLINE/PubMed
spelling pubmed-44562802015-06-09 Distinct Clinicopathological Patterns of Mismatch Repair Status in Colorectal Cancer Stratified by KRAS Mutations Li, Wenbin Zhi, Wenxue Zou, Shuangmei Qiu, Tian Ling, Yun Shan, Ling Shi, Susheng Ying, Jianming PLoS One Research Article In sporadic colorectal cancer (CRC), the BRAF(V600E) mutation is associated with deficient mismatch repair (MMR) status and inversely associated with to KRAS mutations. In contrast to deficient MMR (dMMR) CRC, data on the presence of KRAS oncogenic mutations in proficient MMR (pMMR) CRC and their relationship with tumor progression are scarce. We therefore examined the MMR status in combination with KRAS mutations in 913 Chinese patients and correlated the findings obtained with clinical and pathological features. The MMR status was determined based on detection of MLH1, MSH2, MSH6 and PMS2 expression. KRAS mutation and dMMR status were detected in 36.9% and 7.5% of cases, respectively. Four subtypes were determined by MMR and KRAS mutation status: KRAS (+)/pMMR (34.0%), KRAS (+)/dMMR (2.9%), KRAS (-)/pMMR (58.5%) and KRAS (-)/dMMR (4.6%). A higher percentage of pMMR tumors with KRAS mutation were most likely to be female (49.0%), proximal located (45.5%), a mucinous histology (38.4%), and to have increased lymph node metastasis (60.3%), compared with pMMR tumors without BRAF(V600E) and KRAS mutations (36.0%, 29.3%, 29.4% and 50.7%, respectively; all P < 0.01). To the contrary, compared with those with KRAS(-)/dMMR tumors, patients with KRAS(+)/dMMR tumors demonstrated no statistically significant differences in gender, tumor location, pT depth of invasion, lymph node metastasis, pTNM stage, and histologic grade. This study revealed that specific epidemiologic and clinicopathologic characteristics are associated with MMR status stratified by KRAS mutation. Knowledge of MMR and KRAS mutation status may enhance molecular pathologic staging of CRC patients and metastatic progression in CRC can be estimated based on the combination of these biomarkers. Public Library of Science 2015-06-04 /pmc/articles/PMC4456280/ /pubmed/26042813 http://dx.doi.org/10.1371/journal.pone.0128202 Text en © 2015 Li et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Li, Wenbin
Zhi, Wenxue
Zou, Shuangmei
Qiu, Tian
Ling, Yun
Shan, Ling
Shi, Susheng
Ying, Jianming
Distinct Clinicopathological Patterns of Mismatch Repair Status in Colorectal Cancer Stratified by KRAS Mutations
title Distinct Clinicopathological Patterns of Mismatch Repair Status in Colorectal Cancer Stratified by KRAS Mutations
title_full Distinct Clinicopathological Patterns of Mismatch Repair Status in Colorectal Cancer Stratified by KRAS Mutations
title_fullStr Distinct Clinicopathological Patterns of Mismatch Repair Status in Colorectal Cancer Stratified by KRAS Mutations
title_full_unstemmed Distinct Clinicopathological Patterns of Mismatch Repair Status in Colorectal Cancer Stratified by KRAS Mutations
title_short Distinct Clinicopathological Patterns of Mismatch Repair Status in Colorectal Cancer Stratified by KRAS Mutations
title_sort distinct clinicopathological patterns of mismatch repair status in colorectal cancer stratified by kras mutations
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4456280/
https://www.ncbi.nlm.nih.gov/pubmed/26042813
http://dx.doi.org/10.1371/journal.pone.0128202
work_keys_str_mv AT liwenbin distinctclinicopathologicalpatternsofmismatchrepairstatusincolorectalcancerstratifiedbykrasmutations
AT zhiwenxue distinctclinicopathologicalpatternsofmismatchrepairstatusincolorectalcancerstratifiedbykrasmutations
AT zoushuangmei distinctclinicopathologicalpatternsofmismatchrepairstatusincolorectalcancerstratifiedbykrasmutations
AT qiutian distinctclinicopathologicalpatternsofmismatchrepairstatusincolorectalcancerstratifiedbykrasmutations
AT lingyun distinctclinicopathologicalpatternsofmismatchrepairstatusincolorectalcancerstratifiedbykrasmutations
AT shanling distinctclinicopathologicalpatternsofmismatchrepairstatusincolorectalcancerstratifiedbykrasmutations
AT shisusheng distinctclinicopathologicalpatternsofmismatchrepairstatusincolorectalcancerstratifiedbykrasmutations
AT yingjianming distinctclinicopathologicalpatternsofmismatchrepairstatusincolorectalcancerstratifiedbykrasmutations