Importance of MutL homologue MLH1 and MutS homologue MSH2 expression in Turkish patients with sporadic colorectal cancer.
OBJECTIVE
To assess the incidence of MLH1 (the human MutL homologue) and MSH2 (the human MutS homologue) protein expression in Turkish patients with sporadic colorectal cancers and to compare their survival and clinicopathological features.


METHODS
We validated the tissue microarray technology in 77 colorectal carcinomas by analyzing the immunohistochemical expression of proteins involved in two main pathways of colorectal carcinogenesis: p53 protein for loss of heterozygosity tumors; MLH1 and MSH2 proteins for microsatellite instability (MSI).


RESULTS
Our analysis showed that 29 (39.2%) had loss of MLH1 expression, 5 (6.8%) had loss of MSH2 expression and 2 cases had loss of expression of both proteins. We found that 60% of MSH2-negative tumors were located in the right side of the colon; all MSH2-negative cases were women. In addition, the loss of MSH2 expression was correlated with low p53 expression. Neither MLH1 nor MSH2 expressions were associated with prognosis, although there seemed a tendency of longer survival (71.7 +/- 8.65 mo vs 47.08 +/- 5.26 mo) for the patients with MLH1-negative versus MLH1-positive carcinomas. There were not significant differences in overall and recurrence-free survival among MLH1/MSH2-positive and -negative cases.


CONCLUSIONS
Our data supports that Turkish patients with MLH1- and MSH2-defective tumors have some distinct features from each other. Although prognostic importance remains controversial, immunohistochemical analysis of mismatch repair genes may be used as a routine histopathological examination of sporadic colorectal carcinomas.
Erdamar
Sibel
S
Department of Pathology, Cerrahpasa Medical College, Istanbul University, Cerrahpasa 34303, Istanbul, Turkey. serdamar@hotmail.com
Ucaryilmaz
Esra
E
Demir
Gokhan
G
Karahasanoglu
Tayfun
T
Dogusoy
Gulen
G
Dirican
Ahmet
A
Goksel
Suha
S
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D000328:Adult; D000368:Aged; D015179:Colorectal Neoplasms / Q000378:metabolism / Q000401:mortality / Q000473:pathology / Q000503:physiopathology; D004260:DNA Repair; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D008297:Male; D008875:Middle Aged; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein / Q000235:genetics / Q000378:metabolism*; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D040081:Protein Array Analysis; D015203:Reproducibility of Results; D015996:Survival Rate; D014421:Turkey
D048868:Adaptor Proteins, Signal Transducing; C501486:MLH1 protein, human; D009687:Nuclear Proteins; C497172:MSH2 protein, human; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein