Expression and significance of cyclin D1, p27kip1 protein in bronchioloalveolar carcinoma.

PURPOSE: To investigate the relationship between expression of cell cycle-related protein cyclin D1, p27kip1 and the pathogenesis of bronchioloalveolar carcinoma (BAC) and the value of prediction of prognosis. METHODS: Cyclin D1 and p27kip1 protein were detected by immunohistochemical En Vision method in 43 BACs. RESULTS: The positivity of cyclin D1 in BAC was 65.1% (28/43), which was significantly higher than that in normal pulmonary tissue (0/13), P<0.01. No statistically significant association was found between cyclin D1 expression data and sex, age, tobacco-use history, histologic subtype (mucinous vs nonmucinous), stromal fibrosis, lymph node metastasis, clinical stage or postoperative survival period (P>0.05), while cyclin D1 expression was found to be negatively correlated with tumor size (P<0.05). The positivity of p27kip1 in BACs was 51.2% (22/43), significantly lower than that in normal pulmonary tissue (12/13), P<0.01. p27kip1 expression level was not associated with sex, age, tobacco-use history, tumor size or histologic subtype (P>0.05), but was negatively correlated with stromal fibrosis, lymph node metastasis and clinical stage (P<0.05); and positively associated with postoperative survival period (P<0.01). The survival rate of p27kip1 positive group was significantly higher than that of p27kip1 negative group (P<0.01). No statistically significant correlation was found between cyclin D1 and p27kip1 expression. CONCLUSIONS: Increased cyclin D1 expression and decreased p27kip1 expression are related to the pathogenesis of BAC; decreased p27kip1 expression is associated with metastasis progression; immunodetection of p27kip1 is useful for assessment of prognosis.

Sporadic hemangioblastoma of the kidney: an underrecognized pseudomalignant tumor?

Hemangioblastoma is a benign tumor that can occur sporadically, or in association with von Hippel-Lindau disease in approximately one-quarter of the cases. Only exceptionally does it occur outside the central nervous system. This report describes 2 cases of sporadic renal hemangioblastoma, with 1 patient presenting with hematuria and polycythemia, and the other low back pain. Histologically, the tumors were circumscribed, and composed of sheets of large polygonal cells traversed by arborizing thin-walled blood vessels. Many of the tumor cells showed pleomorphic nuclei, but the mitotic figures were rare. The cytoplasm was eosinophilic, and occasionally finely vacuolated indicating the presence of lipid. The diagnosis of hemangioblastoma was confirmed by negative immunostaining for cytokeratin, and positive staining for α-inhibin, S100, and neuron-specific enolase. This benign neoplasm which can be mistaken for various malignancies such as renal cell carcinoma, epithelioid angiomyolipoma, adrenal cortical carcinoma, and paraganglioma, deserves wider recognition for its occurrence as a primary renal tumor.

Tissue prostate-specific antigen facilitates refractory prostate tumor progression via enhancing ARA70-regulated androgen receptor transactivation.

Despite being well recognized as the best biomarker for prostate cancer, pathophysiologic roles of prostate-specific antigen (PSA) remain unclear. We report here that tissue PSA may be involved in the hormone-refractory prostate cancer progression. Histologic analyses show that the increased tissue PSA levels are correlated with lower cell apoptosis index and higher cell proliferation rate in hormone-refractory tumor specimens. By stably transfecting PSA cDNA into various prostate cancer cell lines, we found that PSA could promote the growth of androgen receptor (AR)-positive CWR22rv1 and high-passage LNCaP (hormone-refractory prostate cancer cells) but not that of AR-negative PC-3 and DU145 cells. Surprisingly, the protease activity of PSA is not crucial for PSA to stimulate growth and promote AR transactivation. We further showed that increased PSA could enhance ARA70-induced AR transactivation via modulating the p53 pathway that results in the decreased apoptosis and increased cell proliferation in prostate cancer cells. Knockdown of PSA in LNCaP and CWR22rv1 cells causes cell apoptosis and cell growth arrest at the G(1) phase. In vitro colony formation assay and in vivo xenografted tumor results showed the suppression of prostate cancer growth via targeting PSA expression. Collectively, our findings suggest that, in addition to being a biomarker, PSA may also become a new potential therapeutic target for prostate cancer. PSA small interfering RNA or smaller molecules that can degrade PSA protein may be developed as alternative approaches to treat the prostate cancer.