Association of current molecular subtypes in urothelial carcinoma with patterns of muscularis propria invasion.

Urothelial carcinoma is subdivided into luminal (L), basal (B), and p53-wild-type (WT) molecular subtypes, with basal and p53-WT groups showing more aggressive course and poor treatment response, respectively. The literature on molecular subtypes of UC includes a mixture of different stages. We investigated the molecular profile and outcome of pure cohort of muscle invasive bladder carcinoma (MIBC) considering two distinct patterns of muscularis propria (MP) invasion. Forty-three cystectomies harboring stage pT2 were retrospectively identified in 18 years. MP invasion was subclassified into patterns 1 (tumor encasing intact detrusor muscle bundles) and 2 (tumor dissecting/replacing detrusor muscle). Using IHC, B/L phenotypes, p53, and Ki67 were assessed, and survival data was collected. Pattern 1 invasion was noted in 16 (37%) and pattern 2 in 27 (63%), with mean age of pattern 1 being 10 years younger. B/L phenotypes were successfully determined in 83.7%; 48.8% and 34.8% revealed L and B phenotypes, respectively (indeterminate phenotype in 16.4%). Pattern 1 was associated with L phenotype (GATA3 and HER-2 expressions: p = 0.02 & p = 0.04, respectively). Ki67 ≥ 5/10HPF was noted in pattern 2 and B phenotype (p = 0.03). B phenotype showed association with p53-WT (p = 0.007). In median follow-up of 60.7 months, 63.6% of pattern 1 cases were alive without disease compared to 32% of pattern 2 (not significant). A panel of CK20 and GATA3 for luminal and CK5/6 and CK14 for basal subtypes can provide reliable molecular classification in UC. Also, morphology of MIBC can predict the molecular phenotype and the behavior of the UC.

Atypical Small Acinar Proliferation: Repeat Biopsy and Detection of High Grade Prostate Cancer.

Purpose. Atypical small acinar proliferation (ASAP) is diagnosed in 1-2% of prostate biopsies. 30-40% of patients with ASAP may be diagnosed with prostate cancer (PCa) on repeat biopsy. Our objective was to examine the association between ASAP and subsequent diagnosis of intermediate/high risk PCa. Materials and Methods. Ninety-six patients who underwent prostate biopsy from 2000 to 2013 and were diagnosed with ASAP were identified. Clinicopathologic features were analyzed. Comparison was made between those with subsequent PCa on repeat biopsy and those with benign repeat pathology. Results. 56/96 (58%) patients had a repeat biopsy. 22/56 (39%) were subsequently diagnosed with PCa. There was no significant difference in patients' characteristics. Presence of HGPIN on initial biopsy was associated with a benign repeat biopsy (68% versus 23%). 17/22 (77%) had Gleason grade (GG) 3+3 disease and only 5/22 (23%) had GG 3+4 disease. Conclusions. 22/56 patients (39%) of patients who underwent a subsequent prostate biopsy following a diagnosis of ASAP were found to have PCa. 77% of these men were diagnosed with GG 3+3 PCa. Only 23% were found to have intermediate risk PCa and no high risk PCa was identified. Immediate repeat prostate biopsy in patients diagnosed with ASAP may be safely delayed. A multi-institutional cohort is being analyzed.

Can effect of finasteride on prostate-specific antigen be used to decrease repeat prostate biopsy?

OBJECTIVES: Patients often undergo multiple prostate biopsies for persistently elevated prostate-specific antigen (PSA) levels. Finasteride decreases serum PSA by approximately 50%. We performed a pilot study to examine the correlation among finasteride, PSA, and PSA density (PSAD) to identify patients who could be excluded from repeat prostate biopsy. METHODS: We performed a prospective study from 2001 to 2002 on 25 men with elevated PSA levels. These patients had prior negative prostate biopsy findings. At study onset, the patients' PSA level and PSAD were measured. Patients were instructed to take finasteride 5 mg for 6 months. PSA and PSAD determination and prostate biopsies were repeated at 6 months and the findings compared with the initial results. RESULTS: The mean patient age was 67.2 years (median 62). The median PSA level was 8.3 ng/dL at study entry (mean 9.34) and 4.6 ng/dL (mean 5.09) at 6 months. The median PSAD was 0.18 (mean 0.20) at study entry and 0.09 (mean 0.12) at 6 months. Of the 23 patients who completed the study, 6 (26%) were diagnosed with prostate cancer. At study entry, the median PSA level in those with prostate cancer was 9.6 ng/dL and was 5.8 ng/dL at 6 months. Patients without prostate cancer on repeat biopsy had a 44% decrease in PSAD. Patients with prostate cancer had a 5% decrease in PSAD. CONCLUSIONS: The results of our study have demonstrated that patients without prostate cancer have a greater decrease in PSAD when taking finasteride than those with prostate cancer. This pilot study had a small population with limited power, and a repeat prospective study with a larger population is warranted.