Clinical significance of heparanase splice variant (t5) in renal cell carcinoma: evaluation by a novel t5-specific monoclonal antibody.

T5 is a novel splice variant of heparanase, an endo-ß-D-glucuronidase capable of cleaving heparan sulfate side chains at a limited number of sites. T5 splice variant is endowed with pro-tumorigenic properties, enhancing cell proliferation, anchorage independent growth and tumor xenograft development despite lack of heparan sulfate-degrading activity typical of heparanase. T5 is over expressed in the majority of human renal cell carcinoma biopsies examined, suggesting that this splice variant is clinically relevant. T5 is thought to assume a distinct three-dimensional conformation compared with the wild type heparanase protein. We sought to exploit this presumed feature by generating monoclonal antibodies that will recognize the unique structure of T5 without, or with minimal recognition of heparanase, thus enabling more accurate assessment of the clinical relevance of T5. We provide evidence that such a monoclonal antibody, 9c9, preferentially recognizes T5 compared with heparanase by ELISA, immunoblotting and immunohistochemistry. In order to uncover the clinical significance of T5, a cohort of renal cell carcinoma specimens was subjected to immunostaining applying the 9c9 antibody. Notably, T5 staining intensity was significantly associated with tumor size (p = 0.004) and tumor grade (p = 0.02). Our results suggest that T5 is a functional, pro-tumorigenic entity.

Degree and Predictors of Functional Loss of the Operated Kidney following Nephron-Sparing Surgery: Assessment by Quantitative SPECT of 99m Tc-Dimercaptosuccinic Acid Scintigraphy.

Purpose. To determine the degree and predictors of renal function loss of the operated kidney following nephron-sparing surgery (NSS). Material and methods. The study group included 113 patients with renal mass who underwent NSS at our institution. QDMSA before and 3-6 months after surgery was used for evaluation differences in renal function of each kidney. Mean change of percent uptake by the kidney was correlated with various clinical and pathological variables. Results. The overall average decrease of renal function of the operated kidney as measured by QDMSA was 10.5% ± 2.6 SER. Among the studied variables, the most important predictors of postoperative ipsilateral residual kidney function were estimated blood loss (EBL), P = 0.0003, duration of warm ischemia, P = 0.008, patient's age at surgery, P = 0.024, method used for tumor bed closure, P = 0.06, and location of the lesion, P = 0.08. Conclusions. Carful hemostasis, minimal duration of arterial clamping, and use of tissue adhesives to seal tumor bed are associated with maximal preservation of postoperative residual renal function after NSS. These variables should be considered by the operative team when planning the surgical procedure .

Positive surgical margin appears to have negligible impact on survival of renal cell carcinomas treated by nephron-sparing surgery.

BACKGROUND: The occurrence of positive surgical margins (PSMs) after partial nephrectomy (PN) is rare, and little is known about their natural history. OBJECTIVE: To identify predictive factors of cancer recurrence and related death in patients having a PSM following PN. DESIGN, SETTING, AND PARTICIPANTS: Some 111 patients with a PSM were identified from a multicentre retrospective survey and were compared with 664 negative surgical margin (NSM) patients. A second cohort of NSM patients was created by matching NSM to PSM for indication, tumour size, and tumour grade. MEASUREMENTS: PSM and NSM patients were compared using student t tests and chi-square tests on independent samples. A Cox proportional hazards regression model was used to test the independent effects of clinical and pathologic variables on survival. RESULTS AND LIMITATIONS: Mean age at diagnosis was 61+/-12.5 yr. Mean tumour size was 3.5+/-2 cm. Imperative indications accounted for 39% (43 of 111) of the cases. Some 18 patients (16%) underwent a second surgery (partial or total nephrectomy). With a mean follow-up of 37 mo, 11 patients (10%) had recurrences and 12 patients (11%) died, including 6 patients (5.4%) who died of cancer progression. Some 91% (10 of 11) of the patients who had recurrences and 83% of the patients (10 of 12) who died belonged to the group with imperative surgical indications. Rates of recurrence-free survival, of cancer-specific survival, and of overall survival were the same among NSM patients and PSM patients. The multivariable Cox model showed that the two variables that could predict recurrence were the indication (p=0.017) and tumour location (p=0.02). No other variable, including PSM status, had any effect on recurrence. None of the studied parameters had any effect on the rate of cancer-specific survival. CONCLUSIONS: PSM status occurs more frequently in cases in which surgery is imperative and is associated with an increased risk of recurrence, but PSM status does not appear to influence cancer-specific survival. Additional follow-up is needed.