Microsatellite Instability in Prostatic Adenocarcinoma: Association with a Mucinous Phenotype
Constantin S Friedman, David J Pisapia, Propa Ghosh, Maria M Shevchuk. NYP-Weill Cornell Medical College, New York, NY; NYP-Columbia University Medical Center, New York, NY; Maimonides Medical Center, Brooklyn, NY
Background: The loss of DNA mismatch repair genes and subsequent microsatellite instability (MSI) plays a key role in carcinogenesis of approximately 15% of colonic carcinomas, including patients with Lynch syndrome, as well sporadic cases. A characteristic histologic feature of MSI-associated colonic carcinomas is mucinous change. Several studies have also shown loss of mismatch repair genes in prostatic adenocarcinomas. However no specific histologic phenotype of this tumor has been described in relation to MSI. We examined prostatic adenocarcinomas with mucinous change for their possible association with MSI.
Design: Index cases consisted of 22 prostatic adenocarcinomas with mucinous extravasation involving at least 5% of the tumor. Control cases consisted of 22 prostatic adenocarcinomas (without mucinous change), matched for primary and secondary Gleason patterns, and for pathologic stage. MSI was studied by immunohistochemical staining for MLH1, MSH2, MSH6, and PMS2 by our Translational Research Laboratory.
Results: The Gleason scores of the set of mucinous tumors and of the matching controls were as follows: 16 cases were Gleason score 7; including 4 cases of 3+4, 7 cases of 4+3, and 5 cases of 4+3 with tertiary pattern 5. Two cases were Gleason score 8(3+5) with tertiary pattern 4, and 4 cases were Gleason score 9(4+5). In each set there was 1 case of stage pT2a, 11 cases of pT2c, 7 cases of pT3a, and 3 cases of pT3b. The mean age of the patients with mucinous adenocarcinoma was 64 (range 46-78), and of the control patients the mean age was 62 (range 54-75). MSH6 was absent in 6 (26%) of the mucinous carcinomas, and in 1 (4.5%) of the control cases. MLH1, MSH2 and PMS2 were retained in all cases. This difference is statistically significant (p=.039).
Conclusions: Mucinous prostatic adenocarcinomas, characterized by the presence of extravasated mucus, are more likely to be associated with MSI, specifically with the loss of MSH6. This suggests that a subset of patients with loss of MSH6 might be at increased risk for prostatic carcinoma; and that the mucinous phenotype may be a histologic indicator. This association is interesting in light of a recent study which reported that MSH6-associated colonic carcinomas appear to be a distinctive subset of MSI-related tumors. If supported by future studies of larger numbers of cases, these observations may help to identify patients with MSI-related prostate cancer.
Category: Genitourinary (including renal tumors)
Monday, March 19, 2012 9:30 AM
Poster Session I Stowell-Orbison/Surgical Pathology/Autopsy Awards Poster Session # 152, Monday Morning