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BACKGROUND Altered expression of CD44 has been implicated in tumor progression and metastasis in multiple neoplasms. METHODS CD44 expression in archival tissues of prostate carcinoma was examined by immunohistochemistry with monoclonal antibodies against core CD44 and the RNA splice variant CD44v6 (v6). RESULTS Core CD44 expression was reduced in the majority of primary neoplastic foci (n = 94) and loss of expression correlated with increasing Gleason grade. Staining for v6 was absent in most carcinomas and metastases. Expression of core CD44 in pelvic lymph node (n = 27) and bone metastases (n = 21) was significantly reduced. In addition, CD44 expression correlated with cytoarchitecture. Tall columnar tumor cells typically stained positively, yet more rounded cells forming cribiform structures or nests showed reduced expression. All cases of high‐grade prostatic intraepithelial neoplasia were positive for core CD44 yet, there was decreased expression in cribiform and micropapillary variants. CONCLUSIONS The majority of clinically relevant human prostatic carcinomas and metastases downregulate expression of CD44. Additional studies to determine whether CD44 cell surface expression relates to clinical outcome independent of other established clinicopathologic risk factors are warranted. Prostate 34:162–168, 1998.© 1998 Wiley‐Liss, Inc.

Residual cancer in radical prostatectomy specimens from men with biopsy-proven adenocarcinoma occasionally may be difficult, or even impossible, to identify. Although this finding was recently described as "minimal residual cancer" or the "vanishing cancer phenomenon," there are no data on the incidence of this phenomenon in surgical pathology practice. We evaluated 3,038 consecutive radical prostatectomies performed at the Johns Hopkins Hospital between 1988 and 1995, excluding cases with a history of transurethral resection, prior therapy with a luteinizing hormone-releasing hormone agonist, focal Gleason grade 4 or 5, capsular penetration, or a positive surgical margin. Of this group, 84 cases with minimal or no residual cancer were identified. In 60 of these cases, residual cancer was "difficult to find" (mean total volume, 0.03 cc; range, 0.01-0.08 cc); in 20 cases, residual cancers were classified as "minute" (mean total volume, 0.07 cc; range, 0.03-0.13 cc). In four cases, no residual cancer could be identified, including two cases in which the diagnosis of cancer on needle biopsy was confirmed, one case in which review of the diagnostic needle biopsy revealed only high-grade prostatic intraepithelial neoplasia, and one case in which molecular analysis demonstrated mislabeling of the needle biopsy specimen. The annual incidence of minimal residual cancer increased from 0.5% in 1988 to 4% in 1993 and has begun to plateau at 3 to 4% since 1993 (p = 0.0016 for increasing trend). These data confirm the general impression that with more vigilant screening of men for prostate cancer, there has been an associated increase in cancer with little or no residual cancer at radical prostatectomy.

We studied 721 men with clinically confined disease who underwent radical prostatectomy. No patient received preoperative or postoperative radiotherapy or hormone therapy until progression occurred. For those men without progression, the mean follow-up was 6.5 years with a median of 6 years (range 1 to 12 years). Because patients with lymph node metastases or seminal vesicle invasion had such a high risk of progression, enhanced prognostication was not needed in men with these findings. Thus we focused this analysis on the 617 men without lymph node metastases or seminal vesicle invasion. In the multivariate analysis, Gleason score (P < 0.0001), surgical margins (P = 0.004), and capsular penetration (P = 0.007) were all independent predictors of progression. Tumors with a Gleason score of 2 through 4 were almost invariably cured, with a 10-year progression-free risk of 96%. At the opposite end of the spectrum, the 10-year actuarial progression-free risk for men with a Gleason score of 8 through 9 was 35%. Men with Gleason score 2 through 4 or 8 through 9 tumors could not be stratified into different risks of progression based on the presence or extent of capsular penetration or margin status. For the men with Gleason score 5 through 7 tumors (88.2% of cases), predicting their risk of progression was enhanced by knowledge of their tumor's capsular penetration and margin status. Tumors with a Gleason score of 5 through 6 and 7 were each stratified into three groups with different risks of progression. Using the actuarial curves within this study, physicians will be able to more accurately determine a patient's risk of progression following radical prostatectomy based on a combination of the radical prostatectomy Gleason score, extent of capsular penetration, and status of surgical margins of resection.

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