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Reduced expression of hMSH2 protein is correlated to poor survival for soft tissue sarcoma patients
Helge W Taubert1, Frank Bartel, Matthias Kappler
1Institute of Pathology, Faculty of Medicine, Martin Luther University Halle-Wittenberg, Halle, Germany. helge.taubert@medizin.uni-halle.de
Background:
Deregulation of DNA mismatch repair is a common mechanism for the development of hereditary nonpolyposis colon carcinoma and related familiar cancers, but it also plays a role in the tumorigenesis of sporadic cancers. Although the protein expression of the two main components of DNA mismatch repair, hMSH2 and hMLH1, has been described in soft tissue sarcoma (STS) patients, its prognostic impact is yet to be determined.
Methods:
The authors investigated the expression of the DNA repair proteins hMSH2 and hMLH1 by Western blot analysis in tumor samples of 57 STS patients. The correlation between the expression of hMSH2/hMLH1 and survival was studied in a Cox proportional hazards regression model, which was adjusted for the prognostic effects of staging, tumor entity, and radicality of tumor resection.
Results:
Nine of 57 STS (16%) showed reduced expression of hMSH2 and reduced expression of hMLH1 was detected in seven STS patients (12%). In a Kaplan-Meier analysis, the median survival for patients with reduced expression of the hMSH2 protein was 18 months, whereas the patients with a normal expression of hMSH2 survived for an average of 68 months. A multivariate Cox proportional hazards regression model revealed a significant correlation between the reduced expression of the hMSH2 protein and poor survival (relative risk = 4.7; 95% confidence interval [CI]: 1.3-17.2; P = 0.019).
Conclusions:
Reduced expression of the hMSH2 protein is an independent negative prognostic factor for STS patients.
Insights
Reduced expression of the human MutS homolog 2 (hMSH2) protein is linked to poorer survival in soft tissue sarcoma (STS) patients. This finding highlights hMSH2 as a significant negative prognostic factor in STS.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Genetics
Background:
- DNA mismatch repair (MMR) pathway is crucial in maintaining genomic stability.
- MMR gene deregulation is implicated in hereditary and sporadic cancers.
- The prognostic significance of MMR proteins hMSH2 and hMLH1 in soft tissue sarcoma (STS) remains unclear.
Purpose of the Study:
- To investigate the expression levels of hMSH2 and hMLH1 proteins in STS.
- To determine the prognostic impact of hMSH2 and hMLH1 expression on patient survival.
Main Methods:
- Western blot analysis was used to assess hMSH2 and hMLH1 protein expression in 57 STS tumor samples.
- Survival analysis was performed using Kaplan-Meier curves and a Cox proportional hazards regression model.
- The Cox model was adjusted for clinical prognostic factors including staging, tumor type, and surgical resection radicality.
Main Results:
- Reduced hMSH2 expression was observed in 16% of STS patients, and reduced hMLH1 in 12%.
- Patients with reduced hMSH2 expression had a median survival of 18 months, compared to 68 months for those with normal expression.
- Multivariate analysis confirmed that reduced hMSH2 expression is a significant independent predictor of poor survival (HR=4.7, P=0.019).
Conclusions:
- Reduced expression of the hMSH2 protein is an independent negative prognostic factor for STS patients.
- hMSH2 expression status could aid in risk stratification and treatment decisions for STS.