Overexpression of HOXC11 homeobox gene in clear cell renal cell carcinoma induces cellular proliferation and is associated with poor prognosis.

Novel evidence has confirmed the involvement of dysregulated expression of HOX genes in cancer. HOX genes are a family of 39 transcription factors, divided in four clusters (HOXA to HOXD), that during normal development regulate cell proliferation and specific cell fate. The aim of this study was to investigate whether genes of the HOXC cluster might play a role in renal cancer. The expression of HOXC11 was detected through polymerase chain reaction and immunohistochemical staining, and we demonstrated that HOXC11 was significantly higher in renal cell carcinoma (RCC) compared to normal kidney tissue. We further demonstrated that HOXC11 overexpression in HK-2 human epithelial cell line promoted proliferation, whereas downregulation of HOXC11 endogenous levels in human RCC cells (Caki-2 cells) decreased proliferation. In RCC, expression of HOXC11 and Ki67, a marker of proliferation, correlates strongly with each other (r s = 0.47, p < 0.003). High immunohistochemical expression of HOXC11 was correlated with T stage (p = 0.06), N stage (p = 0.07), disease stage (p = 0.08), and Ki67 expression (p = 0.07), and patients with tumors showing high number of HOXC11-positive cells had shorter overall survival (p = 0.08) and shorter progression-free survival after treatment (p = 0.08) compared with patients with tumors exhibiting low amount of HOXC11-positive cells. Our data suggest that HOXC11 may contribute to RCC carcinogenesis by increasing tumor cell proliferation and imply that HOXC11 may be an important determinant of RCC patient prognosis.

Elevated microRNA-185 is associated with high vascular endothelial growth factor receptor 2 expression levels and high microvessel density in clear cell renal cell carcinoma.

MicroRNAs (miRNAs) are involved in a number of biological processes, including tumor biology. Previous studies have demonstrated that miRNA-185 regulates signaling downstream of vascular endothelial growth factor receptor 2 (VEGFR-2) and, consequently, angiogenesis. The aim of this study was to analyze the potential relationship between miRNA-185, VEGFR-2, and angiogenesis in samples from renal cell carcinoma (RCC) patients. Tumor tissue was obtained from 82 patients. The miRNA-185 and VEGFR-2 gene expression levels were analyzed by PCR, and the protein concentrations of VEGFR-2 were detected by ELISA. Angiogenesis, visualized by the endothelial cell marker CD34 combined with caldesmon, was assessed by immunohistochemistry and the microvessel density (MVD) technique. In situ hybridization was performed for miRNA-185. Tumors were classified as low or high miRNA-185-expressing using the median as the cutoff. The median gene expression levels of VEGFR-2 were significantly lower in the tumors expressing low levels of miRNA-185, 0.31 (95 % CI, 0.25-0.37), compared to those expressing high levels of miRNA-185, 0.47 (95 % CI, 0.27-0.59), p = 0.02. A positive association was certified with VEGFR-2 protein levels, p = 0.06. The median MVD was significantly lower in the tumors expressing low levels of miRNA-185, 6.8 (95 % CI, 6.33-7.67), compared to those expressing high levels, 8.0 (95 % CI, 6.33-9.00), p < 0.01. miRNA-185 was detected in endothelial cells by in situ hybridization detection. The results suggest that high levels of miRNA-185 in RCC are associated with high VEGFR-2 mRNA and protein levels and a higher density of microvessels. However, further investigation should be performed to analyze the prognostic value of miRNA-185 in RCC.

Increased expression of Chitinase 3-like 1 and microvessel density predicts metastasis and poor prognosis in clear cell renal cell carcinoma.

Increasing evidence demonstrated that Chitinase 3-like 1 (hereafter termed CHI3L1 or YKL-40) was highly expressed and tightly associated with human tumor development and progression. However, its precise role in clear cell renal cell carcinoma (hereafter termed RCC) remains to be delineated. In the present study, we investigated the relationship between CHI3L1 expression and microvessel density (MVD), a reflection of angiogenesis, with metastasis and prognosis in patients with clear cell renal cell carcinoma (RCC). Formalin-fixed, paraffin-embedded tissue sections of clear cell RCC from 73 patients who had undergone radical nephrectomy were stained immunohistochemically with specific antibodies against CHI3L1 and CD34. CHI3L1 immunostaining was semi-quantitatively estimated based on the proportion (percentage of positive cells) and intensity. MVD was determined with CD34-stained slides. The expression pattern of CHI3L1 and MVD was compared with the clinicopathological variables. Twenty patients had either synchronous or metachronous metastases and 12 died during the follow-up. CHI3L1 intensity was significantly correlated with tumor size (P = 0.005), TNM stage (P = 0.027), M stage (P = 0.011), grade (P = 0.014), and metastasis (synchronous or metachronous; P < 0.001). The CHI3L1 proportion (P = 0.038) and MVD (P = 0.012) were significantly correlated with metastasis. MVD was correlated with CHI3L1 intensity (r = 0.376, P = 0.001) and CHI3L1 proportion (r = 0.364, P = 0.002). There was no difference in the expression of CHI3L1 and MVD between primary and metastatic sites. The survival of patients with higher CHI3L1 intensity was significantly worse than that of patients with lower CHI3L1 intensity. Multivariate analyses indicated that only M stage was an independent prognostic factor for cancer-specific survival and CHI3L1 expression was not an independent factor. Taken altogether, increased expression of CHI3L1 and MVD is associated with metastasis and a worse prognosis in clear cell RCC. CHI3L1 expression is correlated with MVD. The results suggest that CHI3L1 may be important in the progression and angiogenesis of clear cell RCC and CHI3L1 might be a novel strategy for therapy of the patients with RCC.

Temporary filters and liver mobilization technique improve the safety and prognosis of radical nephrectomy and inferior vena cava thrombectomy in renal cell carcinoma with subdiaphragmatic thrombosis.

AIMS: This study aimed to investigate the safety and efficacy of preoperative temporary inferior vena cava (IVC) filter placement and intraoperative application of a liver mobilization technique. MATERIALS AND METHODS: The experiment cohort of 42 cases and the control cohort of 36 cases of renal cell carcinoma involving the IVC were analyzed retrospectively. In the experiment cohort, patients were implanted with a temporary IVC filter as routine preoperative treatment. The control cohort of 36 cases received traditional radical nephrectomy + IVC thrombectomy. RESULTS: In the experiment cohort, 42 cases did not show any symptom of tumor thrombus embolism perioperatively. The average operation time was 220 min and the average blood loss was 750 ml. Overall survival rate of improved surgery was significantly higher than traditional surgery (p = 0.0055). Moreover, tumor thrombus size and position was associated with overall survival (p = 0.0185). CONCLUSIONS: Preoperative temporary IVC filter placement and intraoperative application of a liver mobilization technique to expose the IVC can effectively prevent tumor thrombosis embolism shedding and improve surgical safety.

Radiotherapy may improve overall survival of patients with T3/T4 transitional cell carcinoma of the renal pelvis or ureter and delay bladder tumour relapse.

BACKGROUND: Since transitional cell carcinoma (TCC) of the upper urinary tract is a relatively uncommon malignancy, the role of adjuvant radiotherapy is unknown. METHODS: We treated 133 patients with TCC of the renal pelvis or ureter at our institution between 1998 and 2008. The 67 patients who received external beam radiotherapy (EBRT) following surgery were assigned to the radiation group (RT). The clinical target volume included the renal fossa, the course of the ureter to the entire bladder, and the paracaval and para-aortic lymph nodes, which were at risk of harbouring metastatic disease in 53 patients. The tumour bed or residual tumour was targeted in 14 patients. The median radiation dose administered was 50 Gy. The 66 patients who received intravesical chemotherapy were assigned to the non-radiation group (non-RT). RESULTS: The overall survival rates for the RT and non-RT groups were not significantly different (p = 0.198). However, there was a significant difference between the survival rates for these groups based on patients with T3/T4 stage cancer. A significant difference was observed in the bladder tumour relapse rate between the irradiated and non-irradiated bladder groups (p = 0.004). Multivariate analysis indicated that improved overall survival was associated with age < 60 years, T1 or T2 stage, absence of synchronous LN metastases, and EBRT. Acute gastrointestinal and bladder reactions were the most common symptoms, but mild non-severe (> grade 3) hematologic symptoms also occurred. CONCLUSION: EBRT may improve overall survival for patients with T3/T4 cancer of the renal pelvis or ureter and delay bladder tumour recurrence in all patients.

[The clinical characteristic of adrenal metastatic tumor].

OBJECTIVE: To analyze the clinical features of adrenal metastasis. METHODS: From January 1993 to December 2004, 103 cases of adrenal metastasis were reviewed. RESULTS: Lung and hepatocellular carcinoma were the most common primary tumor of adrenal metastatic tumor, which about 36.9% (38/103) and 42.7% (44/103) of all cases, followed by renal carcinoma 6.8% (7/103), colorectal carcinoma 4.9% (5/103), stomach carcinoma 3.9% (4/103), breast cancer 1.9% (2/103), unknown primary tumor 2.9% (3/103). Most of these were low differentiation. The mean diameter of adrenal metastasis was 3.9 cm. The mean interval from detection of primary tumor to adrenal metastasis was 9.5 months. And 79.6% (82/103) were detected as a part of multiorgan metastasis. Only 5 cases (4.9%) were presented with pain in the back. There was little characterization of ultrasonography, CT and MRI, color-Doppler and selective arterial imaging showed little blood supply. All of patients were treated with synthetic methods, 16 cases (15.5%) who had undergone adrenalectomy for metastasis disease had a improved survival compared with those non-adrenalectomy. CONCLUSIONS: There is no particular presentation of clinic and imaging, diagnosis depending on history, follow-up and the pathological presentation of primary tumor. There are no standard treatment guidelines for this group of patients. When the primary tumor could be resected or be well controlled, and there is no other evidence of metastasis, adrenalectomy is recommended. Transarterial chemoembolization (TACE) could not actually be performed.