CXCR4 is highly expressed at the tumor front but not in the center of prostate cancers.

OBJECTIVE: To evaluate the expression of CXCR4, its ligand SDF-1, ß-catenin and E-cadherin throughout the local tumor microenvironment of prostate cancer. PATIENTS AND METHODS: A total of 64 prostate cancer specimens, 24 frozen and 40 paraffin-embedded sections, were obtained from patients treated with radical prostatectomy for clinically localized cancer. Real-time RT-PCR was used for mRNA quantification of CXCR4 and SDF-1 in the tumor center (T), tumor front (F) and distant peritumoral tissue (D). Immunohistochemical analysis was used to investigate the expression patterns of CXCR4, E-cadherin and ß-catenin. Clinical records of these patients were studied for follow-up data, and the prognostic value of these molecules' expression was statistically assessed. RESULTS: CXCR4 mRNA and protein were significantly increased at the tumor front as compared to distant tissue or tumor center. In comparison, SDF-1 mRNA level gradually increased from the tumor center to the distant peritumoral tissue. High CXCR4 at the tumor front was associated with high Gleason score. Low SDF-1 at the tumor front was associated with locally advanced cancer and disease recurrence. Moreover, high CXCR4 staining at the tumor front and increased cytosolic E-cadherin expression in the same location was associated with locally advanced disease. CONCLUSIONS: CXCR4 seems overexpressed at the tumor front of prostate tumors, where it potentially promotes cell migration toward the SDF-1 centrifugal attracting gradient, as well as epithelial-mesenchymal transition. High CXCR4 and low SDF-1 levels at tumor front were both associated with adverse histological features.

Hybrid oncocytic/chromophobe renal cell tumours do not display genomic features of chromophobe renal cell carcinomas.

Hybrid oncocytic/chromophobe tumours (HOCT) are renal tumours recently described displaying histological features of both renal oncocytoma (RO) and chromophobe renal cell carcinoma (ChRCC), raising the question of their precise signification in the RO/ChRCC group. This study aimed to describe clinicopathological features of so called HOCT and to characterise their genomic profile. Five hundred and eighty-three tumours belonging to the ChRCC/RO group were retrospectively reviewed. Twelve tumours that could not be classified as RO or CHRC were considered as HOCT. Hale staining and cytokeratin 7 (CK7) immunostaining were performed. Genomic profile was established by array comparative genomic hybridisation (array-CGH) on frozen samples. Mean age at diagnosis was 70 years (range 46-83). No recurrence was observed (median follow-up: 18 months; range 9-72). Tumour size ranged from 1 to 11 cm. HOCT showed an admixture of RO- and ChRCC-like areas and/or "hybrid" cells with overlapping cytonuclear and/or histochemical features. Hale staining was apical in 50 to 100 % of cells, and CK7 was expressed in 10 to 100 % of cells. Genomic profile was balanced in seven cases or showed a limited number of random imbalances in five cases, as observed in RO. In no instances were observed the characteristic chromosome losses of ChRCC. These results suggest that so called HOCT are not true hybrid tumours and rather could represent a morphological variant of RO. From a diagnostic perspective, an array-CGH analysis could be performed in ambiguous ChRCC/RO cases to formally exclude the diagnosis of ChRCC.