PTEN Losses by Fluorescence In Situ Hybridization (FISH) – but Not Immunohistochemistry – Correlate with Higher Gleason Grade: Prospective Study of 2261 Prostate Needle Biopsies in a Community Practice Setting
David G Bostwick, Harpreet Singh, Deloar Hossain. Bostwick Laboratories, Inc., Orlando, FL; Bostwick Laboratories, Inc., Glen Allen, VA
Background: Genomic deletion of the phosphatase and tensin homolog deleted on chromosome 10 (PTEN) tumor suppressor gene is a significant predictor of aggressiveness in prostate cancer. The correlation of protein expression (immunohistochemistry) and gene expression (fluorescence in situ hybridization (FISH)) with Gleason grade and patient age is uncertain. We evaluated the correlation of these two methods of PTEN analysis with Gleason score and patient age in a prospective study of a large series of biopsy cores from patients in a community urology setting.
Design: PTEN deletion was assayed prospectively in needle biopsy specimens with prostate cancer from 2261 patients in a large national reference laboratory serving community urologists. A single core with the highest Gleason score was chosen for analysis from each case. Immunohistochemistry was used in patients from New York state (n= 415) owing to regulatory restrictions, whereas samples from patients in the remainder of the country were assayed for PTEN deletions by FISH (n= 1846).
Results: PTEN deletion by immunohistochemistry was observed in prostate cancer samples from 110 of 415 (26.5%) patients, significantly more than PTEN deletion by FISH observed in 334 of 1846 cancers (total, 21.1%; hemizygous, 217 [11.8%]; homozygous, 117 [9.3%])(p < 0.0005). PTEN deletion by immunohistochemistry did not correlate with Gleason score (Gleason 6, 7, 8, and 9 in 23.9%, 31%, 25%, and 36.4% cases; p=0.51), whereas PTEN deletion by FISH showed a significant positive correlation (11.8%, 33.0%, 28.2%, and 45.3%, respectively; p, 0.0001). Neither method of PTEN deletion determination was correlated with patient age (both p > 0.1).
Conclusions: The frequency of PTEN deletion in prostate cancer varied from about 12 to 45%, depending on method of determination and Gleason score. There was no correlation with patient age by either method. Given the likely greater impact of tissue fixation on protein overexpression compared with gene expression, PTEN deletion by FISH may be more accurate.
Category: Genitourinary (including renal tumors)
Tuesday, March 5, 2013 1:00 PM
Poster Session IV # 175, Tuesday Afternoon