CD117⁺ cells in the circulation are predictive of advanced prostate cancer.

Circulating tumor cells (CTCs) are associated with cancer progression, aggressiveness and metastasis. However, the frequency and predictive value of CTCs in patients remains unknown. If circulating cells are involved in tumor aggressiveness and metastasis, then cell levels should decline upon tumor removal in localized cancer patients, but remain high in metastatic patients. Accordingly, proposed biomarkers CD117/c-kit, CD133, CXCR4/CD184, and CD34-positive cell percentages in the blood of patients undergoing radical prostatectomy for localized cancer were assessed by flow cytometry prior to intervention and 1-3 months postoperatively. Only circulating CD117⁺ cell percentages decreased after radical prostatectomy, increased with cancer progression and correlated with high PSA values. Notably, postoperative CD117⁺ levels did not decrease in patients experiencing biochemical recurrence. In a xenograft model, CD117-enriched tumors were more vascularized and aggressive. Thus, CD117 expression on CTCs promotes tumor progression and could be a biomarker for prostate cancer diagnosis, prognosis, and/or response to therapy.

The sensitivity of initial transurethral resection or biopsy of bladder tumor(s) for detecting bladder cancer variants on radical cystectomy.

PURPOSE: We determined the ability of bladder biopsy and transurethral resection of the bladder to accurately predict bladder cancer variants on radical cystectomy since certain variants may affect prognosis and treatment. MATERIALS AND METHODS: We retrospectively evaluated the records of 302 patients who underwent biopsy and/or transurethral resection of the bladder followed by radical cystectomy from 2008 to 2010. The frequency of variant morphology and the sensitivity of the precystectomy material was determined using pathological findings at radical cystectomy as the final result. RESULTS: Bladder cancer variants were identified in 159 patients (53%) on initial biopsy/transurethral resection and/or final pathological evaluation at radical cystectomy. The most common variant was urothelial carcinoma with squamous differentiation in 72 of 159 patients (45%), followed by micropapillary urothelial carcinoma in 41 (26%). In 9 patients (6%) variant morphology was identified only on biopsy/transurethral resection bladder and not on final radical cystectomy pathological assessment. The remaining 150 patients (94%) showed variant morphology on radical cystectomy with (79 or 53%) or without (71 or 47%) variant morphology on the preceding biopsy/transurethral resection. The sensitivity of variant detection showed a broad range by variant subtype. Overall, initial biopsy/transurethral resection sensitivity was 39% for predicting variant morphology on radical cystectomy. CONCLUSIONS: Overall sensitivity for predicting bladder cancer variants from biopsy/transurethral resection of the bladder sampling is relatively low. This is likely due to sampling and tumor heterogeneity rather than to an inaccurate pathological diagnosis. Additional predictive markers of variant morphology may be useful to determine which tumors contain aggressive variants that may alter outcomes or therapy.

Clinicopathologic characteristics of 23 cases of invasive low-grade papillary urothelial carcinoma.

OBJECTIVE: To investigate the clinicopathologic and immunohistochemical features associated with invasive low-grade papillary urothelial carcinoma (LGPUC), an uncommon entity not previously described in published studies. METHODS: A multicenter effort originally identified 36 cases diagnosed as invasive LGPUC by urologic pathology subspecialists; after re-review, 23 cases were included. RESULTS: The average patient age was 69 years (range 46-82); 20 patients were men and 3 were women. Stage pT1 disease was present in 19 (83%) of 23 and pT2 disease in 4 patients. Of the 23 cases, 13 (57%) showed a single focus of invasion and 10 multiple foci. The invasive front showed rounded, variably sized nests in 17 cases (74%) and irregular nests with retraction artifact in 6. Additional findings in the noninvasive component included inverted growth in 23, apoptotic debris in 5, focal brisk mitotic activity in 4, dispersed chromatin in individual cells in 4, and a single atypical cell in 2. Immunohistochemical stains showed focal p53 nuclear stain in 23, patchy full-thickness cytokeratin 20 stain in 20, full-thickness CD44 expression in 17, and retention of E-cadherin in 23 cases. Clinical follow-up was available for all patients. The subsequent diagnosis included papilloma in 1 patient (4%), LGPUC in 5 (22%), and high-grade papillary urothelial carcinoma in 8 (35%) of the 23 patients, with 5 demonstrating invasion. Of the latter patients, 2 developed metastatic disease. CONCLUSION: Given the risk of progressive disease in these patients, especially the limited stage pT1 disease in most patients, additional studies investigating the molecular properties and outcomes associated with this uncommon lesion are warranted.

Emerging concepts in micropapillary urothelial carcinoma.

Micropapillary urothelial carcinoma is a relatively uncommon variant of urothelial carcinoma, but its recognition carries important prognostic and treatment implications. Micropapillary morphology occurs in neoplasms arising in many different organ systems and displays aggressive biologic behavior regardless of its site of origin. On account of this association, micropapillary features in urothelial carcinoma should be reported regardless of whether the pattern is focal or dominant. The overall prognosis for micropapillary urothelial carcinoma is poor and recent studies suggest that early treatment with cystectomy could improve outcome, as these tumors are unlikely to respond to chemotherapy when used as a secondary treatment modality. This review discusses the histologic features required for diagnosis and the clinical significance of rendering a diagnosis of micropapillary urothelial carcinoma.