Microsatellite instability and prostate cancer: clinical and pathological implications.

Purpose Of Review: The purpose of this review is to discuss early and recent reports investigating microsatellite instability and mismatch repair expression in prostate cancer.

Recent Findings: Human mismatch repair genes encode highly conserved interacting proteins that suppress genetic instability by correcting misincorporated nucleotides and insertion/deletion mispairs formed during DNA replication. Mismatch repair deficiency causes genetic instability at microsatellite sequences because of the cell's inability to correct errors caused by DNA polymerase slippage at repetitive sequences. Microsatellite instability is characteristic of mismatch repair deficiency, and has been used as a surrogate marker for the inactivation of mismatch repair genes. Inherited mismatch repair gene mutations predispose to gastrointestinal and genitourinary malignancies in a cancer predisposition syndrome known as hereditary non-polyposis colorectal carcinoma. Although strong evidence for an inherited predisposition to prostate cancer does not exist in hereditary non-polyposis colorectal carcinoma, mismatch repair deficiency and mismatch repair gene mutations have been described in sporadic prostate cancer and prostate cancer cell lines. Early reports detected microsatellite instability in prostate cancer, and correlated this genetic alteration to clinical and pathological findings in men diagnosed with this malignancy. Recent reports have identified mismatch repair gene mutations, mismatch repair deficiency and differential mismatch repair gene expression in prostate cancer. In addition, a prognostic role for mismatch repair gene expression in prostate cancer has been suggested.

Summary: The early identification of microsatellite instability in prostate cancer led to more specific investigation of mismatch repair gene expression. Although additional research is required, mismatch repair gene expression may have important biological and clinical significance in prostate cancer.