Reduced expression of hMSH2 protein is correlated to poor survival for soft tissue sarcoma patients.
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.
Taubert
Helge W
HW
Institute of Pathology, Faculty of Medicine, Martin Luther University Halle-Wittenberg, Halle, Germany. helge.taubert@medizin.uni-halle.de
Bartel
Frank
F
Kappler
Matthias
M
Schuster
Katja
K
Meye
Axel
A
Lautenschläger
Christine
C
Thamm-Mücke
Barbara
B
Bache
Matthias
M
Schmidt
Hannelore
H
Holzhausen
Hans-Jürgen
HJ
Würl
Peter
P
D048868:Adaptor Proteins, Signal Transducing; D000328:Adult; D020137:Base Pair Mismatch; D015153:Blotting, Western; D002352:Carrier Proteins; D004260:DNA Repair / Q000235:genetics; D004268:DNA-Binding Proteins; D015536:Down-Regulation; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008198:Lymph Nodes / Q000473:pathology; D008297:Male; D018895:Microsatellite Repeats / Q000235:genetics; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism; D009364:Neoplasm Recurrence, Local / Q000235:genetics / Q000378:metabolism*; D009687:Nuclear Proteins; D011379:Prognosis; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D012509:Sarcoma / Q000378:metabolism* / Q000401:mortality*; D012983:Soft Tissue Neoplasms / Q000378:metabolism* / Q000401:mortality*; D015996:Survival Rate
D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D004268:DNA-Binding Proteins; C501486:MLH1 protein, human; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; C497172:MSH2 protein, human; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein