Reduced expression of hMSH2 protein is correlated to poor survival for soft tissue sarcoma patients

• Published in: Cancer 2003-05, Vol.97 (9), p.2273-2278
• Main Authors: Taubert, Helge W., Bartel, Frank, Kappler, Matthias, Schuster, Katja, Meye, Axel, Lautenschläger, Christine, Thamm‐Mücke, Barbara, Bache, Matthias, Schmidt, Hannelore, Holzhausen, Hans‐Jürgen, Würl, Peter
• Format: Article
• Language: English
• Subjects: Adaptor Proteins, Signal Transducing; Adult; Base Pair Mismatch; Biological and medical sciences; Blotting, Western; Carrier Proteins; Dermatology; DNA Repair - genetics; DNA-Binding Proteins; Down-Regulation; Female; Follow-Up Studies; hMLH1; hMSH2; Humans; Lymph Nodes - pathology; Male; Medical sciences; Microsatellite Repeats - genetics; mismatch repair; MutL Protein Homolog 1; MutS Homolog 2 Protein; Neoplasm Proteins - genetics; Neoplasm Proteins - metabolism; Neoplasm Recurrence, Local - genetics; Neoplasm Recurrence, Local - metabolism; Nuclear Proteins; Prognosis; Proto-Oncogene Proteins - genetics; Proto-Oncogene Proteins - metabolism; Sarcoma - metabolism; Sarcoma - mortality; Soft Tissue Neoplasms - metabolism; Soft Tissue Neoplasms - mortality; soft tissue sarcoma; Survival Rate; Tumors of the skin and soft tissue. Premalignant lesions; Western blot analysis
• ISSN: 0008-543X; 1097-0142
• DOI: 10.1002/cncr.11326

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. Cancer 2003;97:2273–8. © 2003 American Cancer Society. DOI 10.1002/cncr.11326 In this study, the correlation between the expression of the hMSH2 and hMLH1 proteins and the survival of soft tissue sarcoma (STS) patients was investigated. A multivariate Cox proportional hazards regression model revealed a significant correlation between the reduced expression of the hMSH2 protein and poor survival. Reduced expression of the hMSH2 protein is an independent negative prognostic factor for STS patients.