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Cytoplasmic PTEN protein loss distinguishes intraductal carcinoma of the prostate from high-grade prostatic intraepithelial neoplasia

2012; Elsevier BV; Volume: 26; Issue: 4 Linguagem: Inglês

10.1038/modpathol.2012.201

1530-0285

Tamara L. Lotan, Berrak Gümüşkaya, Hameed A. Rahimi, Jessica Hicks, Tsuyoshi Iwata, Brian D. Robinson, Jonathan I. Epstein, Angelo M. De Marzo,

Urologic and reproductive health conditions

Intraductal carcinoma of the prostate is a marker of aggressive disease. However, intraductal carcinoma exists on a morphologic continuum with high-grade prostatic intraepithelial neoplasia (PIN) and distinguishing intraductal carcinoma from PIN is a common diagnostic dilemma with significant clinical implications. We evaluated whether immunostains for PTEN and ERG can sensitively identify intraductal carcinoma and accurately distinguish it from high-grade PIN. 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 PIN lesions (n=39) were retrospectively identified and assessed for PTEN and ERG. 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 PIN (0/39; P 95% and P<0.0001 for each), and substantially less for PIN and the concurrent invasive tumor (83% for PTEN and 67% for ERG; P=NS for each). Cytoplasmic PTEN loss occurs in the majority of intraductal carcinoma and intraductal cribriform proliferation cases. Cytoplasmic PTEN loss was never observed in PIN (100% specificity). Our study identifies PTEN loss as a potentially useful marker to distinguish intraductal carcinoma from PIN and provides a plausible molecular explanation for why intraductal carcinoma is associated with poor prognosis.