Identification of numerical chromosomal changes detected by interphase fluorescence in situ hybridization in high-grade prostate intraepithelial neoplasia as a predictor of carcinoma.
BACKGROUND
High-grade prostate intraepithelial neoplasia (HPIN) is the most likely precursor of prostate cancer. The condition of many patients with a diagnosis of HPIN in prostate needle core biopsy could, if left untreated, progress to invasive cancer. Currently there is no available clinical, immunohistochemical, or morphologic criteria that are predictive of this progression.


OBJECTIVE
To determine whether chromosomal instability in these precursor lesions could increase their predictive value for cancer detection.


METHODS
Dual-color interphase fluorescence in situ hybridization analysis was performed on archived prostate needle core biopsies from 54 patients with initial diagnosis of isolated HPIN and follow-up of 3 years or more. We used commercially available centromere probes for chromosomes 4, 7, 8, and 10. We had interpretable results in 44 patients as follows: (1) group A: 24 HPIN patients with persistent HPIN and/or benign lesions in the follow-up biopsies, and (2) group B: 20 HPIN patients with progression to prostate carcinoma.


RESULTS
Twenty-five percent of the patients in group B displayed numeric chromosomal aberrations. Only 8.3% of the patients from group A had chromosomal abnormalities (P =.1). The observed overall chromosomal changes in HPIN were higher than those in normal or hyperplastic epithelium, with a statistically significant difference (P <.05). All aberrations were detected in the form of chromosomal gain. Overall, the commonest aberration was gain of chromosome 8, followed by gains of chromosomes 7 and 10.


CONCLUSIONS
These results indicated that although no single numeric chromosomal abnormality could be assigned as a predictor of HPIN progression to carcinoma, the overall level of numeric chromosomal abnormalities shows a trend of elevation in HPIN patients whose condition subsequently progressed to carcinoma.
Al-Maghrabi
Jaudah
J
Ontario Cancer Institute, Princess Margaret Hospital, 610 University Ave, Toronto, Ontario, Canada M5G 2M9.
Vorobyova
Lada
L
Toi
A
A
Chapman
William
W
Zielenska
Maria
M
Squire
Jeremy A
JA
D000368:Aged; D002869:Chromosome Aberrations; D006801:Humans; D017403:In Situ Hybridization; D007399:Interphase; D008297:Male; D008875:Middle Aged; D019048:Prostatic Intraepithelial Neoplasia / Q000235:genetics* / Q000473:pathology; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000473:pathology