Digital Quantification of the Cribriform and 7 Other Patterns of Prostate Cancer and Their Association with PSA Failure.
Kenneth A Iczkowski, Kathleen C Torkko, Gregory R Kotnis, R Storey Wilson, Wei Huang, Thomas M Wheeler, Andrea M Abeyta, Francisco G La Rosa, Shelly Cook, Priya N Werahera, M Scott Lucia. University of Colorado Denver, Aurora; University of Wisconsin, Madison; Baylor College of Medicine, Houston, TX
Background: Grading of large acinar (LA) prostate cancer--cribriform and papillary patterns--is controversial. Most pathologists have grown to accept cribriform cancer as grade 4, not 3, but outcome-based data to support proper grading were lacking.
Design: Among 157 men, 76 with PSA failure (≥0.2 ng/mL) were matched to 81 without failure in nearly equal proportions from each of 3 institutions. Primary matching criterion was follow-up interval; secondary criteria were stage, Gleason grade, and patient age. Tumor slides from entire radical prostatectomies were scanned as virtual slides and 9 histologic patterns were digitally traced. Cribriform cancer foci that were small (≤12 lumens) were analyzed separately.
Results: Gleason score (≤6 versus ≥7) was associated with failure (p=0.023), as were stage, margin status, and tumor volume and preoperative PSA, but not patient age or gland volume. Highest pattern frequencies were single, separate acini (98% of specimens), and fused small acini (83%); those of LA patterns were: papillary, 65%, large cribriform, 38%, and small cribriform, 17%. On multivariate analysis, the high-grade pattern whose presence had the highest odds ratio (OR) for PSA failure was cribriform at 6.21 (95% C.I. 2.67 – 14.41, p≤ 0.0001), then papillary (p=0.04) and individual tumor cells (p=0.004), but not fused small acini (p=0.58). Cumulative area sum of cribriform pattern, per additonal mm2, held a 1.18 odds ratio for failure (p=0.007), higher than 1.00 to 1.02 for other high-grade patterns. Men without failure never had > 11.8% cribriform cancer; all 8 men with cribriform area sum ≥25 mm2 had failure (range 33-930).
Presence of both large and small cribriform patterns was linked to failure (p<0.0001, and p=0.0015). For 17 men with >1/3 of cancer area composed of LA cancer, OR was 11.60 (p<0.003), and seminal vesicle invasion was more frequent (p=0.0047). A hypothetical re-grading of cribriform cancer (though non-necrotic) as grade 5 strengthened grade associations with failure.
Fused small acini and individual cells co-occurred significantly, as did papillary and cribriform foci.
Conclusions: Cribriform and papillary cancer should, at least, be graded higher than Gleason 3, regardless of size, to correlate properly with PSA failure, and a cribriform pattern should be mentioned in reports when present. LA patterns may represent a divergent pathway of high-grade tumor development as opposed to fused small acini/ individual cells.
Category: Genitourinary (including renal tumors)
Tuesday, March 1, 2011 11:15 AM
Platform Session: Section A, Tuesday Morning