Tissue microarray analysis of hMSH2 expression predicts outcome in men with prostate cancer.
OBJECTIVE
Mismatch repair genes are responsible for the coordinated correction of misincorporated nucleotides formed during DNA replication. Mismatch repair expression is altered in a subset of prostate cancers (PCs) and a recent study suggested that time to biochemical recurrence following prostatectomy correlated with the degree of hMSH2 immunohistochemical staining. We compared hMSH2 expression and survival in clinically organ confined PC.


METHODS
A prostate tissue microarray was constructed using 243 specimens from patients who underwent radical prostatectomy with extended lymph node dissection for clinically organ confined PC with up to 12 years of followup. Immunohistochemistry was performed with anti-human MSH2 monoclonal antibody. Three independent observers evaluated hMSH2 expression on a scale of 0 to 4. Low expression was defined as a score of less than 2 and high expression was defined as a score of 2 or higher. Statistical analysis used the Fisher exact test, and Goodman and Kruskal gamma coefficient.


RESULTS
Higher Gleason score significantly correlated with higher hMSH2 expression (p < 0.0002). Low hMSH2 expression correlated with increased overall, disease-free and biochemical disease-free survival (all p < 0.01). Analysis comparing low vs high hMSH2 expression was significant with respect to overall (p = 0.0004), disease-free (p = 0.005) and biochemical disease-free (p = 0.0177) survival.


CONCLUSIONS
hMSH2 is differentially expressed in malignant prostate tissue and hMSH2 immunohistochemical staining intensity correlates with Gleason score, overall and disease-free survival. Taken together our results suggest that hMSH2 expression may be a useful prognostic biomarker for outcome in men with clinically organ confined PC.
Prtilo
Alexandra
A
Urology Research Laboratory, Department of Urology, University of Bern, Inselspital, Bern, Switzerland.
Leach
Fredrick S
FS
Markwalder
Regula
R
Kappeler
Andreas
A
Burkhard
Fiona C
FC
Cecchini
Marco G
MG
Studer
Urs E
UE
Thalmann
George N
GN
D014408:Biomarkers, Tumor / Q000032:analysis*; D001707:Biopsy, Needle; D015331:Cohort Studies; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D018572:Disease-Free Survival; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D046228:Microarray Analysis; D051718:MutS Homolog 2 Protein; D009364:Neoplasm Recurrence, Local / Q000235:genetics*; D009367:Neoplasm Staging; D011237:Predictive Value of Tests; D011336:Probability; D011379:Prognosis; D011468:Prostatectomy / Q000379:methods; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000401:mortality* / Q000473:pathology / Q000601:surgery; D011518:Proto-Oncogene Proteins / Q000235:genetics* / Q000378:metabolism; D012189:Retrospective Studies; D018570:Risk Assessment; D012680:Sensitivity and Specificity; D016019:Survival Analysis; D016896:Treatment Outcome
D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; D011518:Proto-Oncogene Proteins; C497172:MSH2 protein, human; D051718:MutS Homolog 2 Protein