Lymph node dissemination is a major prognostic factor in human cancer. However, the molecular mechanisms underlying lymph node metastasis are poorly understood. Recently, vascular endothelial growth factor-C (VEGF-C) was identified as a ligand for VEGF receptor-3 (VEGFR-3/Flt-4) and the expression of VEGFR-3 was found to be highly restricted to the lymphatic endothelial cells. In this report, we investigated the expression of VEGF-C and VEGFR-3 in human prostatic carcinoma tissue by using in situ hybridization and immunohistochemical staining respectively. Expression of VEGF-C mRNA in prostatic carcinoma was significantly higher in lymph node-positive group than in lymph node-negative group. In addition, the number of VEGFR-3-positive vessels was increased in stroma surrounding VEGF-C-positive prostatic carcinoma cells. These results suggest that the expression of VEGF-C in prostatic carcinoma cells is implicated in the lymph node metastasis. © 1999 Cancer Research Campaign

Estrogen, which acts through estrogen receptors (ERs) alpha and beta, has been implicated in the pathogenesis of benign and malignant human prostatic tumors, i.e. benign prostatic hyperplasia and prostate cancer, thought to originate from different zones of the prostate [the transition zone (TZ) and peripheral zone (PZ), respectively]. Here, we examined the cellular distribution of ERalpha and ERbeta in human normal and hyperplastic prostate tissues, using in situ hybridization and immunohistochemistry. ERalpha expression was restricted to stromal cells of PZ. In contrast, ERbeta was expressed in the stromal cells of PZ as well as TZ. ERbeta-positive epithelial cells were evenly distributed in PZ and TZ of the prostate. Our results suggest that estrogen may play a crucial role in the pathogenesis of benign prostatic hyperplasia through ERbeta.

BACKGROUND Human β‐microseminoprotein (β‐MSP or PSP94) is a small protein secreted by prostatic epithelial cells. We recently reported the presence of low levels of β‐MSP mRNA expression and protein in most prostate cancer tissues. METHODS β‐MSP and mRNA expression was examined by in situ hybridization in biopsy specimens obtained from 92 patients with prostate cancer. All tissue specimens were obtained by needle biopsies prior to treatment. All patients subsequently received endocrine therapy. To estimate the influence of β‐MSP mRNA expression and three possible prognostic factors, i.e., patient age, clinical stage, and Gleason score, on time to progression under endocrine therapy, univariate and multivariate analyses were performed using Cox's proportional hazards regression model. RESULTS Multivariate survival analysis showed that clinical stage was the strongest prognostic factor (P =0.006) and that β‐MSP mRNA expression was the second strongest factor (P = 0.038) in 92 patients with stage B–D disease. Analysis of only 51 patients with stage D disease showed that β‐MSP mRNA expression was the only significant prognostic indicator for progression under endocrine therapy (P = 0.003). CONCLUSIONS The presence of cells that express the β‐MSP transcript may be a novel indicator of potentially aggressive prostate cancer. Prostate 38:278–284, 1999. © 1999 Wiley‐Liss, Inc.

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