To characterize the molecular feature in prostate carcinogenesis and the putative transition from prostatic intraepithelial neoplasia (PIN) to invasive prostate cancer (PC), we analyzed gene-expression profiles of 20 PCs and 10 high-grade PINs with a cDNA microarray representing 23,040 genes. Considering the histological heterogeneity of PCs and the minimal nature of PIN lesions, we applied laser microbeam microdissection to purify populations of PC and PIN cells, and then compared their expression profiles with those of corresponding normal prostatic epithelium also purified by laser microbeam microdissection. A hierarchical clustering analysis separated the PC group from the PIN group, except for three tumors that were morphologically defined as one very-high-grade PIN and two low-grade PCs, suggesting that PINs and PCs share some molecular features and supporting the hypothesis of PIN-to-PC transition. On the basis of this hypothesis, we identified 21 up-regulated genes and 63 down-regulated genes commonly in PINs and PCs compared with normal epithelium, which were considered to be involved in the presumably early stage of prostatic carcinogenesis. They included AMACR, OR51E2, RODH, and SMS. Furthermore, we identified 41 up-regulated genes and 98 down-regulated genes in the transition from PINs to PCs; those altered genes, such as POV1, CDKN2C, EPHA4, APOD, FASN, ITGB2, LAMB2, PLAU, and TIMP1, included elements that are likely to be involved in cell adhesion or the motility of invasive PC cells. The down-regulation of EPHA4 by small interfering RNA in PC cells lead to attenuation of PC cell viability. These data provide clues to the molecular mechanisms underlying prostatic carcinogenesis, and suggest candidate genes the products of which might serve as molecular targets for the prevention and treatment of PC.

In chromophobe renal cell carcinoma (RCC), two forms of typical and eosinophilic variants have been reported to date. We have previously reported a new variant of chromophobe RCC, namely an oncocytic variant. However, little is known on the histological features of this variant. In this article, we report such five cases. Macroscopically, the tumor was well demarcated, but unencapsulated. The cut surface of the tumor showed brown in color, but neither hemorrhage nor necrosis was seen. Microscopically, the tumor consisted of predominant tubular configuration with or without various proportion of solid-sheet pattern. In one tumor, tumor cells microscopically invaded branches of renal vein. In addition, the constituting cells were characterized by the oncocytic cytoplasm, trivial to minimal variation in tumor size, indistinct to slightly distinct cell border, centrally located round nuclei and the absence of perinuclear halo. These characteristics entirely resembled renal oncocytoma. However, neoplastic cells immunohistochemically showed the diffuse and strong labeling for cytokeratin 7 and mitochondrial antigen in all cases. In addition, in fluorescence in situ hybridization (FISH) study the loss of more than four chromosomes among chromosomes 7, 10, 13, 17 and 21 was confirmed in all tumors and the diagnosis of chromophobe RCC was rendered. In conclusion, we propose a new variant, namely an oncocytic variant, of chromophobe RCC morphologically resembling renal oncocytoma and biologically showing characteristics of chromophobe RCC, and this recognition is practically crucial in the differential diagnosis from renal oncocytoma.

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Background: We previously reported favorable results of intraarterial doxorubicin chemotherapy in combination with low‐dose radiotherapy for locally‐advanced bladder cancer. We have now designed a new intraarterial chemotherapy regimen to achieve a higher tumor response rate while preserving a functional bladder. Methods: Twenty‐one patients with muscle‐invasive bladder cancer (T2, lO; T3,7; T4,4) were treated with concurrent intraarterial chemotherapy and radiotherapy after an initial complete transurethral resection. Induction therapy consisted of concomitant pirarubicin (THP; 15 mg/m2/day on days 1 to 3), cisplatin (CDDP; 25 mg/m2/day on days 8 to 10) and irradiation (2 Gy/session on days 1 to 3 and 8 to 10). Maintenance treatment consisted of THP administered at 20 or 30 mg with or without 50 mg CDDP every month for 2 years. Results: Nineteen of the 21 patients (90.5|X%) achieved a complete response (CR). One of these 19 relapsed with lung metastases 24 months after treatment and was treated surgically. The 2 patients who did not achieve a CR died of cancer, while the remaining 19 patients are alive with preservation of a functional bladder. Conclusion: These findings suggest that a higher tumor response rate with bladder preservation for patients with muscle‐invasive bladder cancer is achieved by intraarterial THP/CDDP chemotherapy plus radiotherapy.