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Mismatch Repair Gene Expression as a Predictor of Tumor Responses in Patients With Rectal Cancer Treated With Preoperative Chemoradiation

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ABSTRACT

This study evaluated the predictive and prognostic value of expression of mismatch repair (MMR) protein, including MLH1, MSH2, and MSH6 in rectal cancer patients with preoperative chemoradiotherapy.

MMR protein expression was measured by immunohistochemistry in both pretreatment biopsies (pre-) and pathologic specimens (post-) from 209 patients with locally advanced rectal cancer who underwent preoperative chemoradiotherapy and radical surgery. The patients were followed for a median period of 44 months.

A pathologic complete response (pCR) was observed in 30 patients (14.4%). The expression levels of MLH1, MSH2, and MSH6 were not significantly different between the pCR and non-pCR groups. A multivariate analysis revealed that tumor differentiation, postoperative chemotherapy, and pre-MSH6 expression were independent predictors of overall survival; ypN category and perineural invasion were independent predictors of disease-free survival. The pre-MSH6 expression was significantly associated with tumor budding and expression of all MMR proteins. On multivariate analysis, ypN category and post-MSH6 expression were independent predictors for local recurrence.

In our study, we observed the independent prognostic value of MSH6 expression in pretreatment tissue on overall survival and MSH6 expression after chemoradiation on local recurrence. Constitutive MSH6 expression before and after preoperative therapy may be a useful tool for prediction of oncologic outcome in locally advanced rectal cancer.

No MeSH data available.


Immunohistochemical expression of pretreatment MSH6 expression. A, Low expression. B, High expression.
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Figure 1: Immunohistochemical expression of pretreatment MSH6 expression. A, Low expression. B, High expression.

Mentions: Statistical evaluation was carried out using the statistical package SPSS for Windows (Version 14.0; SPSS Inc, Chicago, IL). MMR protein expression levels were classified as negative for <10 % nuclear staining, and positive for ≥10% nuclear staining.9 For positive expression, MMR proteins were divided into low for <90% (median value of MMR expression) nuclear staining, and high for ≥90% nuclear staining (Figure 1). Analysis of clinicopathologic features among the groups was performed using the Student t test and the χ2 test as appropriate. Survival was assessed by the Kaplan–Meier method and differences between curves were evaluated using the log-rank test. The variables with statistically significant P values on univariate analysis were entered into a multivariate analysis using the Cox model. A value of P <0.05 was considered statistically significant.


Mismatch Repair Gene Expression as a Predictor of Tumor Responses in Patients With Rectal Cancer Treated With Preoperative Chemoradiation
Immunohistochemical expression of pretreatment MSH6 expression. A, Low expression. B, High expression.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4998290&req=5

Figure 1: Immunohistochemical expression of pretreatment MSH6 expression. A, Low expression. B, High expression.
Mentions: Statistical evaluation was carried out using the statistical package SPSS for Windows (Version 14.0; SPSS Inc, Chicago, IL). MMR protein expression levels were classified as negative for <10 % nuclear staining, and positive for ≥10% nuclear staining.9 For positive expression, MMR proteins were divided into low for <90% (median value of MMR expression) nuclear staining, and high for ≥90% nuclear staining (Figure 1). Analysis of clinicopathologic features among the groups was performed using the Student t test and the χ2 test as appropriate. Survival was assessed by the Kaplan–Meier method and differences between curves were evaluated using the log-rank test. The variables with statistically significant P values on univariate analysis were entered into a multivariate analysis using the Cox model. A value of P <0.05 was considered statistically significant.

View Article: PubMed Central - PubMed

ABSTRACT

This study evaluated the predictive and prognostic value of expression of mismatch repair (MMR) protein, including MLH1, MSH2, and MSH6 in rectal cancer patients with preoperative chemoradiotherapy.

MMR protein expression was measured by immunohistochemistry in both pretreatment biopsies (pre-) and pathologic specimens (post-) from 209 patients with locally advanced rectal cancer who underwent preoperative chemoradiotherapy and radical surgery. The patients were followed for a median period of 44 months.

A pathologic complete response (pCR) was observed in 30 patients (14.4%). The expression levels of MLH1, MSH2, and MSH6 were not significantly different between the pCR and non-pCR groups. A multivariate analysis revealed that tumor differentiation, postoperative chemotherapy, and pre-MSH6 expression were independent predictors of overall survival; ypN category and perineural invasion were independent predictors of disease-free survival. The pre-MSH6 expression was significantly associated with tumor budding and expression of all MMR proteins. On multivariate analysis, ypN category and post-MSH6 expression were independent predictors for local recurrence.

In our study, we observed the independent prognostic value of MSH6 expression in pretreatment tissue on overall survival and MSH6 expression after chemoradiation on local recurrence. Constitutive MSH6 expression before and after preoperative therapy may be a useful tool for prediction of oncologic outcome in locally advanced rectal cancer.

No MeSH data available.