p53 status correlates with the differential expression of the DNA mismatch repair protein MSH2 in non-small cell lung carcinoma.
We examined the p53 status of 108 NSCLCs compared to the expression of MLH1 and MSH2 proteins. p53 overexpression was demonstrated by IHC in 64% of patients examined, whereas p53 mutations were detected in 43%. Twenty-two percent of mutations were located outside of the hot-spot (exons 5-8) area. p53 mutations and overexpression were more frequent in SCCL (57% and 73%, respectively) than in lung adenocarcinomas (22% and 50%, respectively). In NSCLC-carrying wild-type p53, increased expression of MSH2 correlated with p53 overexpression (p = 0.018). In addition, in SCCL, p53 mutations correlated with reduced MSH2 expression (p = 0.019). These data suggest a relationship between p53 and MSH2. While there is evidence for p53 being a transcriptional activator of MSH2, the hypothesis that MSH2 acts as a DNA-damage signaller triggering p53 overexpression needs to be clarified in future studies.
Xinarianos
George
G
Molecular Oncology Unit, Roy Castle International Centre for Lung Cancer Research, Liverpool, United Kingdom.
Liloglou
Triantafillos
T
Prime
Wendy
W
Sourvinos
George
G
Karachristos
Andreas
A
Gosney
John R
JR
Spandidos
Demetrios A
DA
Field
John K
JK
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D020137:Base Pair Mismatch / Q000235:genetics*; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D004260:DNA Repair; D004268:DNA-Binding Proteins; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D006801:Humans; D007124:Immunoenzyme Techniques; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D051718:MutS Homolog 2 Protein; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D011379:Prognosis; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*
D004268:DNA-Binding Proteins; D011518:Proto-Oncogene Proteins; D016159:Tumor Suppressor Protein p53; C497172:MSH2 protein, human; D051718:MutS Homolog 2 Protein