Concordance for ERG and PTEN in Matched Primary and Metastatic Prostate Cancer: Further Evidence That PTEN Loss Occurs Subsequent to ERG Gene Fusion in Prostate Cancer
Berrak Gumuskaya, Bora Gurel, Jessica L Hicks, Tamara L Lotan, Angelo De Marzo. Johns Hopkins Medical Institutions, Baltimore, MD
Background: Studies of the natural history of tumor initiation and progression are critical for understanding the molecular pathobiology of cancer. A recent study from our group has determined that while ERG expression by IHC tends to be homogeneous in an individual tumor nodule, PTEN loss is often heterogeneous suggesting that ERG rearrangement generally occurs prior to PTEN loss (Lab Invest, 92, Supp 1, 210A, 2012). To test this hypothesis further we used IHC to examine the rate of concordance between these markers in the index tumor from a radical prostatectomy (RRP) specimen and that of a corresponding metastatic lesion found in a pelvic lymph node at the time of RRP. In addition, we examined whether staining for each marker was homogeneous or heterogeneous in the primary and metastatic lesions.
Design: Two tissue microarray blocks were constructed from matched primary (index tumor) and metastatic carcinomas from pelvic lymph nodes from 63 patients that had undergone radical prostatectomy at The Johns Hopkins Hospital. The carcinoma focus with the largest volume and/or highest grade was selected as the index tumor.
Results: 62% (N=37/60) of primary and 60% (N=36/60) of metastatic tumors present on the TMAs were positive for ERG and none of the cases had heterogeneous staining. 44% (28/63) of primary and 40% (23/58) of the metastatic tumors showed PTEN loss. The fraction of cases showing heterogenous PTEN staining in the primary tumor was 13.3% (8/60) and for the metastatic tumors it was 3.7% (2/54). The proportion of cases that were concordant for staining for ERG in the primary and metastatic lesions was 98.3% (57/58) and for PTEN it was 84.2% (49/57), and these proportions were statistically significantly different (P = 0.0073, two sample test of proportions).
Conclusions: The finding of highly concordant ERG staining in the index and metastatic tumor is supportive of the hypothesis that the index tumor and the metastatic lesion are clonally related (as seen previously by Guo et al. Hum Pathol. 43:644-9, 2012). The decreased concordance between PTEN loss in the primary and metastatic lesions as compared to ERG, along with the heterogeneity of PTEN staining, provides additional support for the contention that PTEN loss occurs at a later stage than ERG rearrangement during the natural history of prostate cancer evolution.
Monday, March 4, 2013 1:00 PM
Poster Session II # 265, Monday Afternoon