| Background and Objective:In china, prostate cancer (PC) is one of the most common malignant neoplasm in male urinary system, the proportion of prostate cancer is9.7%in male malignant carcinoma. Unfortunately, the natural course of prostate cancer is long and the clinical symptom is concealing. In addition, it is impossible for everyone to screen. Many patients were discovered in advanced stage. Assessment and monitoring of pelvic lymph node metastasis is a difficulty to prostate cancer. Recent studies have confirmed that hypoxia, neovessels and lymphangiogenesis play a great role in the genesis, development and metastasis of malignant carcinoma. Under hypoxic conditions, hypoxia-inducible factor-la (HIF-1α) is an important regulator of in the process of angiogenesis, cell proliferation, and energy metabolism. Vascular endothelial growth factor-C (VEGF-C) is the first cytokine of lymphangiogenesis factors which were discovered, also known as the lymphatic growth factor; VEGF-C can induce lymphangiogenesis and promote the malignant progression and lymph node metastasis of tumor. HIF-1α and VEGF-C is closely linked to the occurrence, development and metastasis of tumor. By immunohistochemistry, we detected the expression of HIF-1α and VEGF-C in prostatic cancer and benign prostate hyperplasia (BPH) tissue, and with the clinical data we analyzed its relationship with the Gleason score, clinical staging, the lymph node metastasis and patient’s PSA level of prostatic cancer. We also analyzed the correlation between the expressions of HIF-1α and VEGF-C in prostatic carcinoma. We would like to find out how HIF-1α and VEGF-C play a important role in the occurrence, development and metastasis of prostate cancer, to provide reference for the clinical prediction of lymph node metastasis and prognosis.Materials and Method:A totally of72patients of prostatic disease from department of urology, second hospital of Tianjin medical university undergoing surgical resection or TURP treatment, containing13cases benign prostatic hyperplasia(BPH) and59cases prostatic carcinoma(PC),with accession from June2005to February2011and confirmed pathologically, were included in this study. The average age of this two groups is (60.8±7.54years) and (63.2±9.55years). No demonstrable difference was found in average age between two groups (t=1.738, P>0.05). Strept Actividin-Biotin Complex (SABC) method was used to detect the expression of HIF-la and VEGF-C in BPH and PC tissues. According to the TNM stages, Gleason score and the state of lymph node metastasis divide the59prostatic carcinoma samples into different groups. Staining steps were carried out according to kit instructions, and we choose positive breast and colorectal cancer histological section as positive control of HIF-1α and VEGF-C respectively, with PBS replaced the antibody as negative control. The results were observed by light microscope and brown or yellow-tan particles in cells were considered as positive cases. SPSS16.0software application was used for all analysis and statistical significance was defined as P values less than0.05.Results:(1) In prostatic tissue, HIF-la expressed mainly in nuclei, and VEGF-C was mainly in cytoplasm. HIF-la positive stained rate was significant higher in PC (66.1%) than that in BPH (7.7%). VEGF-C positive stained rate was significant higher in PC (76.3%) than that in BPH (0). There were significant differences between PC group and BPH group (P<0.01).(2) Dividing the59prostatic carcinoma samples into groups according to clinicopathological features, we found that was associated with clinical stages and Gleason score. With the increase of clinical stages and Gleason score, their expressions in cell also rose up, and it was statistically significant (P<0.05). In prostatic cancer tissue with lymphatic metastasis, HIF-la and VEGF-C expressed moderately to strong positive, and the staining positive percentage is higher than the tissue without lymphatic metastasis (P<0.05). The expression of HIF-1α and VEGF-C, however, did not show any correlations to the patient’s age and PSA level (P>0.05).(3) In33cases of PC, the staining of HIF-la and VEGF-C is positive commonly. Using Spearman Rank Correlation Test, there was a positive correlation between the expressions of HIF-la and VEGF-C in prostatic carcinoma (r=0.261, P<0.05).Conclusion:(1) HIF-1α and VEGF-C were upregulated in prostatic carcinoma. There was significant difference between the PC and BPH. This abnormality suggested that HIF-la and VEGF-C should play a role in the genesis of prostate tumor.(2) The expression of HIF-la and VEGF-C in PC were correlated with clinical stages, histological grade and lymph node metastasize, which indicating that HIF-1α and VEGF-C participated the process of development and metastasis in PC. Those tumors which were highly expressed HIF-1α and VEGF-C would be severe malignant, high invasive and high risk of lymph node metastasis.(3) In PC, the expression of HIF-1α protein had positive correlation with that of VEGF-C. It is possible for them to make synergistic action during the tumorigenesis, progression and lymph node metastasis of PC.(4) Testing HIF-1α and VEGF-C together may be a valuable parameter for judging disease severity and prognosis. |
