The International Society of Urological Pathology 2012 Consensus Conference made recommendations regarding classification, prognostic factors, staging, and immunohistochemical and molecular assessment of adult renal tumors. Issues relating to prognostic factors were coordinated by a workgroup who identified tumor morphotype, sarcomatoid/rhabdoid differentiation, tumor necrosis, grading, and microvascular invasion as potential prognostic parameters. There was consensus that the main morphotypes of renal cell carcinoma (RCC) were of prognostic significance, that subtyping of papillary RCC (types 1 and 2) provided additional prognostic information, and that clear cell tubulopapillary RCC was associated with a more favorable outcome. For tumors showing sarcomatoid or rhabdoid differentiation, there was consensus that a minimum proportion of tumor was not required for diagnostic purposes. It was also agreed upon that the underlying subtype of carcinoma should be reported. For sarcomatoid carcinoma, it was further agreed upon that if the underlying carcinoma subtype was absent the tumor should be classified as a grade 4 unclassified carcinoma with a sarcomatoid component. Tumor necrosis was considered to have prognostic significance, with assessment based on macroscopic and microscopic examination of the tumor. It was recommended that for clear cell RCC the amount of necrosis should be quantified. There was consensus that nucleolar prominence defined grades 1 to 3 of clear cell and papillary RCCs, whereas extreme nuclear pleomorphism or sarcomatoid and/or rhabdoid differentiation defined grade 4 tumors. It was agreed upon that chromophobe RCC should not be graded. There was consensus that microvascular invasion should not be included as a staging criterion for RCC.

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OBJECTIVE• To assess the expression of the androgen receptor (AR) and oestrogen receptors (ERs) in bladder tumours because recent studies have shown confl icting results and the prognostic signifi cance of their expression remains unclear. PATIENTS AND METHODS• We investigated the expression of AR, ER α and ER β in 188 bladder tumour specimens, as well as matched 141 non-neoplastic bladder and 14 lymph node metastasis tissues, by immunohistochemistry.• We then evaluated the relationships between their expression and the clinicopathological features available for the present patient cohort. RESULTS• AR/ER α /ER β was positive in 80%/50%/89% of benign urothelium, 50%/67%/41% of benign stroma, 42%/27%/49% of primary tumours and 71%/64%/71% of metastatic tumours.• Signifi cantly lower expression of AR/ER α was found in high-grade tumours (36%/23%) and tumours invading muscularis propria (33%/19%) compared to low-grade tumours (55%; P = 0.0232/38%; P = 0.0483) and tumours not invading muscularis propria (51%; P = 0.0181/35%; P = 0.0139), respectively.• Signifi cantly higher expression of ER β was found in high-grade tumours (58%) and tumours invading muscularis propria (67%) compared to low-grade tumours (29%; P = 0.0002) and tumours not invading muscularis propria (34%; P < 0.0001), respectively.• Kaplan -Meier and log-rank tests further showed that positivity of ER β (but not AR or ER α ) was associated with the recurrence of low-grade tumours ( P = 0.0072); the progression of low-grade tumours ( P = 0.0005), high-grade tumours not invading muscularis propria ( P = 0.0020) and tumours invading muscularis propria ( P = 0.0010); or disease-specifi c mortality in patients with tumours invading muscularis propria ( P = 0.0073). CONCLUSIONS• Compared to benign bladders, a signifi cant decrease in the expression of AR, ER α or ER β in bladder cancer was seen.• Loss of AR or ER α was strongly associated with higher grade/more invasive tumours, whereas ER β expression was increased in high-grade/invasive tumours and predicted a worse prognosis.

androgen deprivation therapy ͉ testosterone ͉ TGF␤1 ͉ metastasis E arly studies suggested that the prostatic epithelial androgen receptor (AR), when activated by androgens, increased cellular proliferation (1, 2). Clinical studies also pointed out that androgen deprivation therapy (ADT) with suppression of androgens/AR functions, is an effective treatment for most prostate cancer patients (3, 4). However, most prostate tumors regrow after 12-18 months of continuous ADT (1-4). The detailed mechanisms of why suppression of androgens/AR ultimately fails and cancers recur as a more aggressive type and metastasize remain unclear.The conventional concept of the AR role in prostate cancer is to promote cancer progression, and positive AR staining can be found in many prostate tumors even at the later stages. In addition to androgens, other factors could also affect AR activity, such as (a) AR mutations or amplification, (b) changes in AR and AR coregulators interactions, or (c) growth factors/kinases signal pathways that activate AR activity at the castration level of androgen (1-4). However, why patients receiving ADT tended to have an earlier development of more aggressive types of cancer and whether AR has a differential role in different prostatic cells and/or in different prostate cancer stages remain unclear.Here, we report the generation of a mouse cancer model lacking the AR only in its prostatic epithelium (pes-ARKO-TRAMP), which develops prostate cancer spontaneously with an intact immune system. Notably, through AR gain-and loss-of-function in epithelial-stromal cell coculture and coimplantation experiments, we demonstrated that the AR could function in epithelial basal intermediate cells as a tumor suppressor to suppress prostate cancer metastasis, in epithelial luminal cells as a surviving factor, and in stromal cells as a proliferator to stimulate cancer progression. These contrasting data challenge the currently used ADT that systematically suppresses androgen actions, and thus reduces both proliferative and suppressor functions of AR. Our results suggest the need for better therapies that only target the proliferative function of AR.

Small cell carcinoma of the prostate (SCPC) is morphologically similar to small cell carcinoma of the lung (SCLC) and maybe misinterpreted as Gleason pattern 5b prostate adenocarcinoma (HGPC). Recognition of SCPC is important because of its different clinical behavior. This study aims to characterize the immunophenotype of histologically classic SCPC using a comprehensive panel of markers, to better understand its histogenesis, aid in its classification, and evaluate potential therapeutic targets. Using the World Health Organization morphologic criteria for SCLC, 18 SCPC cases were identified; and studied for the following tumor marker groups: prostate specific/related, neuroendocrine, sex steroid hormone receptors, and prognostic/treatment target-related. Ten cases of UPC were used as controls. PSA was positive in 17% of SCPC and neuroendocrine markers were expressed in HGPC. PSA, TTF-1 and CD56 were the most helpful markers in differentiating between SCPC and HGPC (P<0.01), whereas bombesin/GRP, c-kit, bcl-2, and EGFR expression was more frequent in SCPC. SCPC is best diagnosed by following the World Health Organization diagnostic criteria for SCLC. Immunohistochemical markers can help separate SCPC from HGPC and may be useful in histologically borderline cases. Potential therapeutic targets are identified immunohistochemically in SCPC (Bombesin/GRP, c-kit, bcl-2, and EGFR).