Expression of HIF-2a in clear-cell renal cell carcinoma independently predicts overall survival.

The purpose of this study is to evaluate the expression and the prognostic role of main factors, involved in the hypoxia pathway, in patients with clear-cell renal cell carcinoma (ccRCC). Immunohistochemical expression of Hypoxia inducible factors (HIF) HIF-1a, HIF-2a, prolyl hydroxylases PHD1, PHD2, PHD3, and factor inhibiting HIF (FIH) was assessed on a tissue microarray, containing tumour and corresponding normal kidney tissue from 66 patients underwent surgery for ccRCC. Expression levels were evaluated in relation to T stage, Fuhrman grade, cancer-specific, and overall survival (OS). Cytoplasmatic expression of HIF-2a was positively correlated with expression of HIF-1a (p = 0.011). HIF-1a expression was also positively correlated with PHD3 and FIH (p = 0.020 and p = 0.039). Expression of HIF-1a was associated with lower Fuhrman grade (p = 0.008), while HIF-2a overexpression with unfavourable grade (p = 0.026). PHD3 was significant downregulated (84.8%). Age, LDH, presence of necrosis, Fuhrman grade, T stage, and HIF-2a cytoplasmatic expression were significant associated with OS of patients in univariable analysis. In multivariable analysis, HIF-2a expression (p = 0.006) and T stage (p = 0.001) remained as the only independent predictors for overall survival. These results indicate that HIF-2a overexpression not only is inversely correlated with Fuhrman grade in ccRCC, but also represents a strong independent prognostic factor for a poor overall survival.

Hypoxia-Inducible Factor 2a Expression Is Positively Correlated With Gleason Score in Prostate Cancer.

BACKGROUND: One of the main factors in response to hypoxia in the tumor microenvironment is the hypoxia-inducible factor (HIF) pathway. Although its role in other solid tumors, particularly renal cell carcinoma, has been sufficiently elucidated, it remains elusive in prostate cancer. The aim of the present study was to investigate the expression of main proteins involved in this pathway and determine the correlation of the results with clinicopathological outcomes of patients with prostate cancer. METHODS: The immunohistochemical expression of HIF-1a, HIF-2a and their regulators, prolyl hydroxylase domain (PHD)1, PHD2 and PHD3 and factor inhibiting HIF (FIH), was assessed on a tissue microarray. This was constructed from radical prostatectomy specimens, involving both tumor and corresponding adjacent non-tumoral prostate tissues from 50 patients with localized or locally advanced prostate cancer. RESULTS: In comparison with non-tumoral adjacent tissue, HIF-1a exhibited an equal or lower expression in 86% of the specimens (P = 0.017), while HIF-2a was overexpressed in 52% (P = 0.032) of the cases. HIF-1a protein expression was correlated with HIF-2a (P < 0.001), FIH (P = 0.004), PHD1 (P < 0.001), PHD2 (P < 0.001) and PHD3 (P = 0.035). HIF-2a expression was positively correlated with Gleason score (P = 0.017) and International Society of Urological Pathologists (ISUP) grade group (P = 0.022). CONCLUSIONS: The findings of the present study suggest a key role for HIF-2a in prostate cancer, as HIF-2a expression was found to be correlated with Gleason score and ISUP grade of the patients. However, further studies are required to validate these results and investigate the potential value of HIF-2a as a therapeutic target in prostate cancer.

mRNA overexpression of prolyl hydroxylase PHD3 is inversely related to nuclear grade in renal cell carcinoma.

The aim of the present study was to evaluate the relative mRNA expression levels of genes involved in the hypoxia inducible factor (HIF) signalling pathway in renal cell carcinoma (RCC) and to analyse their associations with clinicopathological parameters and survival outcomes. Reverse transcription-quantitative PCR was used to quantify the mRNA expression levels of HIF-1α, HIF-2α, prolyl hydroxylase (PHD)1, PHD2 and PHD3 in formalin-fixed paraffin-embedded (FFPE) tumour tissue samples from 41 patients with RCC, including 33 cases of clear cell RCC (ccRCC). FFPE samples of corresponding adjacent normal kidney tissues were used as a comparison. mRNA expression levels were analysed in regard to clinical parameters, histological type, stage, nuclear grade, cancer specific survival and overall survival. Compared with adjacent normal kidney tissue, HIF-1α levels were lower in 16/33 ccRCC samples (48.48%), while HIF-2α, PHD1 and PHD2 levels did not exhibit a specific expression pattern. By contrast, the PHD3 mRNA level was higher in 29/33 (87.87%) of the tumour samples. HIF-1α was positively associated with HIF-2α, PHD1 and PHD2. HIF-2α levels were associated with PHD1, PHD2 and PHD3, while PHD3 was strongly associated with PHD2. PHD3 mRNA levels were inversely associated with nuclear grade (P=0.015). However, in univariate analysis, PHD3 was not associated with cancer-specific or overall survival rates. The present findings suggest an important involvement of PHD3 in ccRCC, since PHD3 mRNA expression was inversely associated with nuclear grade. However, PHD3 mRNA levels did not have an independent prognostic value. Further studies are required to investigate whether PHD3 could be used as either a therapeutic target or prognostic marker.

Papillary cystadenoma of epididymis: Is there a need for further investigation in unilateral cases?

INTRODUCTION: The presence of a mass in the epididymis is not a common entity. The papillary cystadenoma of epididymis is a benign tumor which may occur sporadically or as a characteristic of von Hippel-Lindau disease. PRESENTATION OF CASE: We present a case of a 27-year-old man with a right scrotal mass who was treated with surgical excision. Histopathological examination revealed a clear cell epididymal papillary cystadenoma. A computed tomography scan that was performed later showed no other abnormality or any signs of von Hippel-Lindau disease. DISCUSSION: In this report, a case of a young man suffering from this rare tumor is discussed, focusing on the need of further evaluation in order to determinate if it occurs as a feature of VHL disease or as a sporadic form. CONCLUSION: In unilateral cases of papillary cystadenoma of epididymis such as our patient's, literature advocates that no further examinations and expensive genetic testing is required.