Cytoplasmic PTEN Protein Loss Distinguishes Intraductal Carcinoma of the Prostate from High Grade Prostatic Intraepithelial Neoplasia
Tamara L Lotan, Berrak Gumuskaya, Hameed Rahimi, Jessica L Hicks, Tsuyoshi Iwata, Brian D Robinson, Jonathan I Epstein, Angelo M De Marzo. Johns Hopkins Medical Institutions, Baltimore, MD
Background: Intraductal carcinoma of the prostate has long been recognized as a powerful marker of aggressive disease. However, intraductal carcinoma exists on a morphologic continuum with high grade prostatic intraepithelial carcinoma (PIN), a very common intraepithelial lesion that in most cases does not even warrant re-biopsy. Thus, distinguishing intraductal carcinoma from high grade PIN on prostate needle biopsies is a common diagnostic dilemma with significant clinical implications. We evaluated whether immunostains for PTEN and ERG can identify intraductal carcinoma and accurately distinguish it from high grade PIN.
Design: A combined immunostain for PTEN, ERG, p63 and CK903 was developed and validated. Radical prostatectomy specimens with lesions meeting criteria for intraductal carcinoma (n=45), intraductal cribriform proliferations falling short of intraductal carcinoma (n=15), and high grade PIN lesions (n=39) were retrospectively identified and assessed for PTEN and ERG.
Results: Cytoplasmic PTEN loss was identified in 84% (38/45) of the intraductal carcinoma and 100% (15/15) of intraductal cribriform proliferation cases. In contrast, cytoplasmic PTEN loss was never observed in high grade PIN (0/39) (p<0.0001). Of the 53 cases of intraductal carcinoma or intraductal cribriform proliferation with cytoplasmic PTEN loss, it was homogeneously lost in 42 cases (79%). Weak, focal nuclear positivity for PTEN was retained in 31 of these 42 cases (74%). ERG expression was identified in 58% (26/45) of intraductal carcinomas and 67% (10/15) of intraductal cribriform proliferations compared to 13% (5/39) of high grade PIN. Concordance between the PTEN/ERG status of the intraductal carcinoma lesions and the concurrent invasive carcinoma was high (>95% and p<0.0001 for each), and substantially less for high grade PIN and the concurrent invasive tumor (83% for PTEN and 67% for ERG; p=NS for each).
Conclusions: Cytoplasmic PTEN loss occurs in the majority of intraductal carcinoma and intraductal cribriform proliferation cases. Retention of focal nuclear PTEN suggests that at least one allele of PTEN is frequently intact. PTEN loss was never observed in uncomplicated high grade PIN (100% specificity). Our study identifies PTEN loss as a clinically useful marker to distinguish intraductal carcinoma from high grade PIN on prostate needle biopsy and provides a plausible molecular explanation for why intraductal carcinoma is strongly associated with poor prognosis in prostate cancer.
Category: Genitourinary (including renal tumors)
Tuesday, March 5, 2013 9:30 AM
Poster Session III # 63, Tuesday Morning