Patterns of differentiation and proliferation in intraductal carcinoma of the prostate: Significance for cancer progression

Abstract

BACKGROUND: Cribriform prostatic intraepithelial neoplasia (C-PIN) identifies a unique histological pattern: dysplastic cells line ductal/acinar walls but also span across gland lumens. C-PIN is distinct from other forms of dysplasia; it is seldom seen except within invasive cancer, it is more frequent in larger/higher-grade cancers; and it appears to contribute independently to aggressive behavior. Hence, C-PIN may represent a separate, more aggressive entity: intraductal carcinoma of the prostate (IDC-P). Here, support for that distinction stems from a histologic/biologic subclassification of IDC-P, whose elements are linked to features of invasive cancer. METHODS: Histologic criteria were tested against 26 radical prostatectomies, using immunostains for prostate-specific antigen, MUC-2, androgen receptor (differentiation), and Ki-67 (proliferation). Invasive cancer grade, stage, and follow-up were compared. RESULTS: Architecture of the central (luminal) cell compartment defined three subclasses of IDC-P: A (trabecular), B (cribriform), and C (solid/comedo), which represented progressive dedifferentiation with a reciprocal increase in proliferation. The IDC-P subpattern correlated with cancer stage, grade, and clinical course. CONCLUSIONS: IDC-P is a separate entity, distinct from PIN; cancers associated with IDC-P are more aggressive than those associated with only PIN. It comprises a spectrum of histological patterns which appear to be determined in concert with invasive cancer, whose prognosis it worsens.