Distinction between intraductal carcinoma of the prostate (IDC-P), high-grade dysplasia (PIN), and invasive prostatic adenocarcinoma, using molecular markers of cancer progression

BACKGROUND Prostate ducts and acini whose lumens are filled with malignant cells represent a well‐recognized histological pattern recently termed intraductal carcinoma of the prostate (IDC‐P). These tumors are often associated with rapid disease progression, and most recur after radical surgery. Controversy exists as to whether IDC‐P should be recognized as a separate entity, an extension of high‐grade dysplasia (PIN) or invasive carcinoma as described by the Gleason grading system. This study investigates the use of molecular markers in defining the position of IDC‐P in the evolutionary hierarchy of prostate cancer progression. METHODS IDC‐P, high‐grade dysplasia, and invasive cancers from a cohort of 20 selected radical prostatectomy specimens were screened for loss of heterozygosity (LOH), using 12 polymorphic microsatellite markers frequently lost in prostate cancer. RESULTS LOH was absent in Gleason grade 3 cancer, infrequent in high‐grade dysplasia (9%) and Gleason grade 4 cancer (29%), but common in IDC‐P (60%). In IDC‐P, and to a lesser extent Gleason grade 4 cancers, multiple sites of allelic loss in individual cases were usual. CONCLUSIONS Allelic instability provides further evidence that IDC‐P is not a simple extension of dysplasia, nor does it represent invasion of Gleason grade 3 cancers into the ductal/acinar system. IDC‐P and Gleason grade 4 cancer represent late but possibly separate events in prostate cancer evolution. Prostate 44:265–270, 2000. © 2000 Wiley‐Liss, Inc.