Quadruple Immunostain for PTEN, ERG and Basal Cell Markers Distinguishes Intraductal Carcinoma of the Prostate from High Grade PIN on Needle Biopsy
Tamara L Lotan, Jeong S Han, Jessica L Hicks, Ming Zhou, Cristina Magi-Galluzzi, Jonathan I Epstein, Angelo M De Marzo. Johns Hopkins Medical Institutions, Baltimore, MD; Cleveland Clinic, Cleveland, OH
Background: Distinguishing intraductal carcinoma from high grade PIN on prostate needle biopsies is a common diagnostic dilemma with significant clinical implications. Using radical prostatectomies, we demonstrated that cytoplasmic PTEN protein loss occurs with high frequency in intraductal carcinoma and accurately distinguishes it from high grade PIN. Here, we tested whether a quadruple immunostain for PTEN, ERG and basal cell markers is diagnostically useful in distinguishing intraductal carcinoma from high grade PIN in prostate needle biopsy specimens.
Design: A combined immunostain for PTEN, ERG, p63 and CK903 was validated and applied retrospectively to prostate needle biopsy specimens containing intraductal carcinoma with concurrent invasive tumor (n=30), isolated intraductal carcinoma (n=10) and intraductal proliferations more concerning than high grade PIN but falling short of criteria for intraductal carcinoma (n=13). As controls, biopsies containing high grade PIN sampled either with (n=7) or without (n=12) concurrent carcinoma in additional cores were also studied.
Results: Intraductal carcinoma occurring with concurrent invasive tumor showed the highest rate of PTEN loss, with 73% (22/30) of intraductal lesions lacking cytoplasmic PTEN protein. Of these, 73% (16/22) were ERG positive, compared to 25% (2/8) of the intraductal carcinoma lesions expressing PTEN (p=0.03, Fisher's exact test). Of the biopsies containing isolated intraductal carcinoma, 60% (6/10) showed PTEN protein loss, with 100% (6/6) of these expressing ERG. In contrast, none of the PTEN-positive isolated intraductal carcinoma cases expressed ERG protein (0/4). Of the intraductal proliferations falling short of intraductal carcinoma, 46% (6/13) showed PTEN protein loss, and 83% (5/6) of these cases expressed ERG. None of the PTEN-positive intraductal proliferations expressed ERG protein (0/7). In contrast, of the high grade PIN cases occurring either with or without concurrent carcinoma in additional cores, 0% (0/19) showed PTEN protein loss and 0% (0/19) showed ERG protein expression.
Conclusions: PTEN loss is common in intraductal carcinoma sampled on needle biopsy yet does not occur in morphologically-identified high grade PIN occurring with or without concurrent invasive carcinoma. ERG protein expression, as reported previously, is generally concordant with PTEN protein loss and, combined with PTEN immunostaining, helps to identify intraductal carcinoma and distinguish it from high grade PIN.
Category: Genitourinary (including renal tumors)
Tuesday, March 5, 2013 9:30 AM
Poster Session III # 65, Tuesday Morning