Absence of hMLH1 or hMSH2 expression as a stage-dependent prognostic factor in sporadic colorectal cancers

Ji Won Park, Hee Jin Chang, Sohee Park, Byung Chang Kim, Dae Yong Kim, Ji Yeon Baek, Sun Young Kim, Jae Hwan Oh, Hyo Seong Choi, Sung Chan Park, Seung-Yong Jeong

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Abstract

Background: The predictive role of mismatch repair (MMR) status for survival after sporadic colorectal cancer remains a point of controversy. This study was designed to test the prognostic value of MMR status in sporadic colorectal cancers. Methods: The study included 318 patients with sporadic colorectal cancer who underwent primary tumor resection. MMR status was determined by the immunohistochemical analysis of hMLH1 and hMSH2 expression. Results: Thirty-six carcinomas (11.3%) showed abnormal MMR protein expression (22 hMLH1 negative and 14 hMSH2 negative) and were classified as MMR-defective tumors. An MMR defect was strongly associated with a reduced likelihood of lymph node (odds ratio, 0.32; 95% confidence interval [95% CI], 0.13-0.75) or distant organ metastases at diagnosis (odds ratio, 0.07; 95% CI, 0.01-0.62), independent of the clinicopathological features. Overall survival was significantly better in patients with MMR-defective tumors than in those with MMR-intact tumors (P = 0.013). In the subgroup analysis by stage, adjusted for other potential confounding variables, MMR status was not a statistically significant prognostic factor in stage I and II patients, while the MMR defect predicted a significantly better overall survival in stage III and IV patients (adjusted hazard ratio, 0.23; 95% CI, 0.06-0.97; P = 0.045). Conclusions: At initial diagnosis, metastases were found at lower rates in MMR-defective tumors. MMR status may be a stage-dependent prognostic factor in patients with sporadic colorectal cancer.

Original languageEnglish
Pages (from-to)2839-2846
Number of pages8
JournalAnnals of Surgical Oncology
Volume17
Issue number11
DOIs
StatePublished - 1 Nov 2010

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DNA Mismatch Repair
Colorectal Neoplasms
Confidence Intervals
Neoplasms
Survival
Odds Ratio
Neoplasm Metastasis
Confounding Factors (Epidemiology)
Lymph Nodes

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Park, Ji Won ; Chang, Hee Jin ; Park, Sohee ; Kim, Byung Chang ; Kim, Dae Yong ; Baek, Ji Yeon ; Kim, Sun Young ; Oh, Jae Hwan ; Choi, Hyo Seong ; Park, Sung Chan ; Jeong, Seung-Yong. / Absence of hMLH1 or hMSH2 expression as a stage-dependent prognostic factor in sporadic colorectal cancers. In: Annals of Surgical Oncology. 2010 ; Vol. 17, No. 11. pp. 2839-2846.
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title = "Absence of hMLH1 or hMSH2 expression as a stage-dependent prognostic factor in sporadic colorectal cancers",
abstract = "Background: The predictive role of mismatch repair (MMR) status for survival after sporadic colorectal cancer remains a point of controversy. This study was designed to test the prognostic value of MMR status in sporadic colorectal cancers. Methods: The study included 318 patients with sporadic colorectal cancer who underwent primary tumor resection. MMR status was determined by the immunohistochemical analysis of hMLH1 and hMSH2 expression. Results: Thirty-six carcinomas (11.3{\%}) showed abnormal MMR protein expression (22 hMLH1 negative and 14 hMSH2 negative) and were classified as MMR-defective tumors. An MMR defect was strongly associated with a reduced likelihood of lymph node (odds ratio, 0.32; 95{\%} confidence interval [95{\%} CI], 0.13-0.75) or distant organ metastases at diagnosis (odds ratio, 0.07; 95{\%} CI, 0.01-0.62), independent of the clinicopathological features. Overall survival was significantly better in patients with MMR-defective tumors than in those with MMR-intact tumors (P = 0.013). In the subgroup analysis by stage, adjusted for other potential confounding variables, MMR status was not a statistically significant prognostic factor in stage I and II patients, while the MMR defect predicted a significantly better overall survival in stage III and IV patients (adjusted hazard ratio, 0.23; 95{\%} CI, 0.06-0.97; P = 0.045). Conclusions: At initial diagnosis, metastases were found at lower rates in MMR-defective tumors. MMR status may be a stage-dependent prognostic factor in patients with sporadic colorectal cancer.",
author = "Park, {Ji Won} and Chang, {Hee Jin} and Sohee Park and Kim, {Byung Chang} and Kim, {Dae Yong} and Baek, {Ji Yeon} and Kim, {Sun Young} and Oh, {Jae Hwan} and Choi, {Hyo Seong} and Park, {Sung Chan} and Seung-Yong Jeong",
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Park, JW, Chang, HJ, Park, S, Kim, BC, Kim, DY, Baek, JY, Kim, SY, Oh, JH, Choi, HS, Park, SC & Jeong, S-Y 2010, 'Absence of hMLH1 or hMSH2 expression as a stage-dependent prognostic factor in sporadic colorectal cancers', Annals of Surgical Oncology, vol. 17, no. 11, pp. 2839-2846. https://doi.org/10.1245/s10434-010-1135-8

Absence of hMLH1 or hMSH2 expression as a stage-dependent prognostic factor in sporadic colorectal cancers. / Park, Ji Won; Chang, Hee Jin; Park, Sohee; Kim, Byung Chang; Kim, Dae Yong; Baek, Ji Yeon; Kim, Sun Young; Oh, Jae Hwan; Choi, Hyo Seong; Park, Sung Chan; Jeong, Seung-Yong.

In: Annals of Surgical Oncology, Vol. 17, No. 11, 01.11.2010, p. 2839-2846.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Absence of hMLH1 or hMSH2 expression as a stage-dependent prognostic factor in sporadic colorectal cancers

AU - Park, Ji Won

AU - Chang, Hee Jin

AU - Park, Sohee

AU - Kim, Byung Chang

AU - Kim, Dae Yong

AU - Baek, Ji Yeon

AU - Kim, Sun Young

AU - Oh, Jae Hwan

AU - Choi, Hyo Seong

AU - Park, Sung Chan

AU - Jeong, Seung-Yong

PY - 2010/11/1

Y1 - 2010/11/1

N2 - Background: The predictive role of mismatch repair (MMR) status for survival after sporadic colorectal cancer remains a point of controversy. This study was designed to test the prognostic value of MMR status in sporadic colorectal cancers. Methods: The study included 318 patients with sporadic colorectal cancer who underwent primary tumor resection. MMR status was determined by the immunohistochemical analysis of hMLH1 and hMSH2 expression. Results: Thirty-six carcinomas (11.3%) showed abnormal MMR protein expression (22 hMLH1 negative and 14 hMSH2 negative) and were classified as MMR-defective tumors. An MMR defect was strongly associated with a reduced likelihood of lymph node (odds ratio, 0.32; 95% confidence interval [95% CI], 0.13-0.75) or distant organ metastases at diagnosis (odds ratio, 0.07; 95% CI, 0.01-0.62), independent of the clinicopathological features. Overall survival was significantly better in patients with MMR-defective tumors than in those with MMR-intact tumors (P = 0.013). In the subgroup analysis by stage, adjusted for other potential confounding variables, MMR status was not a statistically significant prognostic factor in stage I and II patients, while the MMR defect predicted a significantly better overall survival in stage III and IV patients (adjusted hazard ratio, 0.23; 95% CI, 0.06-0.97; P = 0.045). Conclusions: At initial diagnosis, metastases were found at lower rates in MMR-defective tumors. MMR status may be a stage-dependent prognostic factor in patients with sporadic colorectal cancer.

AB - Background: The predictive role of mismatch repair (MMR) status for survival after sporadic colorectal cancer remains a point of controversy. This study was designed to test the prognostic value of MMR status in sporadic colorectal cancers. Methods: The study included 318 patients with sporadic colorectal cancer who underwent primary tumor resection. MMR status was determined by the immunohistochemical analysis of hMLH1 and hMSH2 expression. Results: Thirty-six carcinomas (11.3%) showed abnormal MMR protein expression (22 hMLH1 negative and 14 hMSH2 negative) and were classified as MMR-defective tumors. An MMR defect was strongly associated with a reduced likelihood of lymph node (odds ratio, 0.32; 95% confidence interval [95% CI], 0.13-0.75) or distant organ metastases at diagnosis (odds ratio, 0.07; 95% CI, 0.01-0.62), independent of the clinicopathological features. Overall survival was significantly better in patients with MMR-defective tumors than in those with MMR-intact tumors (P = 0.013). In the subgroup analysis by stage, adjusted for other potential confounding variables, MMR status was not a statistically significant prognostic factor in stage I and II patients, while the MMR defect predicted a significantly better overall survival in stage III and IV patients (adjusted hazard ratio, 0.23; 95% CI, 0.06-0.97; P = 0.045). Conclusions: At initial diagnosis, metastases were found at lower rates in MMR-defective tumors. MMR status may be a stage-dependent prognostic factor in patients with sporadic colorectal cancer.

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U2 - 10.1245/s10434-010-1135-8

DO - 10.1245/s10434-010-1135-8

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