Role of MMP-2, MMP-9 and VEGF as serum biomarker in early prognosis of renal cell carcinoma

Introduction: Renal cell carcinoma epitomizes a diversified group of tumors which contributes more than 15,000 deaths annually worldwide. In spite of tremendous efforts to identify prognostic factors apart from grade, histology and tumor size, they are not so obvious yet to fulfill the requirement. In this study, the prognostic role of serum matrix metalloproteinase (MMP)-2, 9, and vascular endothelial growth factor (VEGF) levels in patients with pre and postoperative renal cell carcinoma are evaluated to use as biomarker.Patients and methods: A total of 100 patients with a diagnosis of renal cell carcinoma included in the study. Additionally, hundred healthy kidney donors enrolled as control, serum MMP-2, MMP-9, and VEGF levels were analyzed in the serum of post and preoperative patients and parallel in control serum samples by ELISA method.Result: Most of the patients with RCC were found to have high concentrations of serum MMP-2, MMP-9, and VEGF. The levels of MMP-2 in the serum of preoperative patients ranged from 627 to 1117 ng/ml (833.90 ± 111.91), postoperative MMP-2 range 302–913 (553.02 ± 150.08), control range 122–384 (228.33 ± 72.52). In MMP-9 pre-operative range 619–1233 (862.32 ± 119.77), post-operative range 124–909 (552.88 ± 151.91) and control range 42–467 (245.44 ± 116.52 and in VEGF preoperative range was 0.792–2.214 (1.35 ± 0.36), postoperative range was 0.315–1.917 (0.81 ± 0.46) and in control it was 0.01–0.39 (0.10 ± 0.09). We observed that preoperative levels of all three markers, were significantly increased if compared with postoperative and control levels (P = 0.001) however, no any significant correlation found when the levels correlated with grade, stage, size, and type for MMP-2 and MMP-9, but VEGF shows some significance in comparison

Polymorphism of GSTM1 and GSTT1 genes in prostate cancer: A study from North India

BACKGROUND: Glutathione-S-transferases (GSTs) are active in the detoxification of wide variety of endogenous or exogenous carcinogens. The genetic polymorphisms of GSTM1 and GSTT1 genes have been studied earlier to evaluate the relative risk of various cancers. AIM, SETTING AND DESIGN: In the present study, we examined the association of the GSTM1 and GSTT1 gene polymorphisms with sporadic prostate cancer patients in north Indian population. MATERIAL AND METHODS: This case control study was undertaken over a period of 24 months and included 103 prostate cancer patients and 117 controls; both patients and controls originated from northern part of India. The GSTT1 and GSTM1 genotypes were identified by multiplex PCR in peripheral blood DNA samples. STATISTICAL ANALYSIS: Difference in genotype prevalence and association between case and control group were assessed by the Chi square and Fisher Exact tests. RESULTS: Frequencies of null genotypes in GSTT1 and GSTM1, was 11% (13/117) and 30% (35/117) respectively in control individuals. The frequencies of GSTT1 and GSTM1 null genotypes in prostate cancer patients were 34% (35/103) and 53% (55/103) respectively. CONCLUSION: Our study demonstrates that the null genotypes of GSTT1 and GSTM1 are substantially at higher risk for prostate carcinoma as compared to the normal healthy controls. The GSTT1 and GSTM1 null genotypes did not show significant association with tobacco usage in prostate cancer patients. However, the null genotypes were significantly stratified in 50-60 year-old patients when incidence of prostate cancer is high

Prognosticfactors in patients with renal cell carcinoma: Is TNM (1997) staging relevant in Indian subpopulation?

BACKGROUND: RCC (Renal Cell Carcinoma) is a common genitourinary malignancy, but its behavior has not been studied in the Indian Subpopulation. AIMS: The aim of this study was to assess the validity of 1997 AJCC TNM staging in Indian subpopulation and also to identify independent predictors for survival in patients having RCC. SETTING AND DESIGN: Retrospective uncontrolled analysis of patients with RCC was performed at our centre. MATERIAL AND METHODS: Medical records of patients of undergoing radical nephrectomy at our center between 1994 to August 2003 were identified retrospectively. Medical records of 178 patients were available for analysis. Patient characteristics, preoperative imaging and surgical details were reviewed. Each tumor was staged according to the 1997 AJCC TNM classification. Nuclear grade was assigned according to the Fuhrman\u2032s grading system. STATISTICAL METHODS: Statistical analysis was performed using statistical software and descriptive statistics and survival functions were obtained. Univariate and multivariate analysis of factors affecting outcome of the patient were performed. RESULTS: Mean follow up period was 42.3 months (range 3 to 108 months). Stage wise 5-year Cancer specific survival was 87.2% in stage 1 disease, 74.3% in stage 2, 36.4% in stage 3 and 3.1% in stage 4. Univariate analysis revealed that stage, grade and lymph node status were statistically significant (P=0.009, 0.007 and 0.003 respectively). Sub-classifying stage 1 tumors between tumor of less than 4 cm. and more than 4 cm. did not reveal any statistically significant difference in survival (P=0.32). Multivariate analysis model revealed that Fuhrman\u2032s grade and lymph node status were statistically significant (P=0.007 and 0.002 respectively). CONCLUSION: This study validates the TNM (1997) staging for RCC as having significant survival impact in the Indian subpopulation. Sub-classifying stage 1 tumors between tumor of less than 4 cm. and more than 4 cm is not of much importance. Nuclear grade and lymph node involvement are important independent predictors of survival. Organ confined tumors with high nuclear grades need to be followed up more rigorously

Does extended lymph node dissection affect the lymph node density and survival after radical cystectomy?

Background : Diagnostic and therapeutic importance of pelvic lymph node (LN) dissection (PLND) in radical cystectomy (RC) has gained recent attention. A method of pathological analysis of LN affects total number of LN removed, number of LN involved, and LN density. Objective : To compare extended lymphadenectomy to standard lymphadenectomy in terms of LN yield, density, and effect on survival. Materials and Methods : From Jan 2004 - July 2009, 78 patients underwent RC whose complete histopathological report was available for analysis. All were transitional cell carcinoma. From July 2007 onward extended LN dissection was started and LNs were sent in six packets. Twenty-eight patients of standard PLND kept in group I. Group II had 23 patients of standard PLND (LN sent in four packets), and group III had 23 patients of extended PLND (LN sent in six packets). SPSS 15 software used for statistical calculation. Results : Distribution of T-stage among three groups is not statistically significant. Median number of LN harvested were 5 (range, 1-25) in group I, 9 (range, 3-28) in group II, and 16 (range, 1-25) in group III. Although this is significant, we did not find significant difference in number of positive LN harvested. We did not find any patient with skip metastasis to common iliac LN in group 3. Conclusions : Separate package LN evaluation significantly increased the total number of LN harvested without increasing the number of positive LN and survival

Does extended lymph node dissection affect the lymph node density and survival after radical cystectomy?

Background : Diagnostic and therapeutic importance of pelvic lymph node (LN) dissection (PLND) in radical cystectomy (RC) has gained recent attention. A method of pathological analysis of LN affects total number of LN removed, number of LN involved, and LN density. Objective : To compare extended lymphadenectomy to standard lymphadenectomy in terms of LN yield, density, and effect on survival. Materials and Methods : From Jan 2004 - July 2009, 78 patients underwent RC whose complete histopathological report was available for analysis. All were transitional cell carcinoma. From July 2007 onward extended LN dissection was started and LNs were sent in six packets. Twenty-eight patients of standard PLND kept in group I. Group II had 23 patients of standard PLND (LN sent in four packets), and group III had 23 patients of extended PLND (LN sent in six packets). SPSS 15 software used for statistical calculation. Results : Distribution of T-stage among three groups is not statistically significant. Median number of LN harvested were 5 (range, 1-25) in group I, 9 (range, 3-28) in group II, and 16 (range, 1-25) in group III. Although this is significant, we did not find significant difference in number of positive LN harvested. We did not find any patient with skip metastasis to common iliac LN in group 3. Conclusions : Separate package LN evaluation significantly increased the total number of LN harvested without increasing the number of positive LN and survival

Impact of delay in inguinal lymph node dissection in patients with carcinoma of penis

Aim: To study the impact of delay in inguinal lymph node dissection (LND) in patients with squamous cell carcinoma of the penis, who have indications for LND at the time of presentation. Materials and Methods: In total, 28 patients (mean age 52.1 ± 12.8 years) with squamous cell carcinoma of the penis, treated from January 2000 to June 2008, were retrospectively studied with regard to clinical presentation, time of LND, and the outcome. The patients were divided into two groups based on the time for LND. Group 1 patients had LND at mean of 1.7 months (range 0-6 months) of treatment of the primary lesion, and group 2 had LND at a mean of 14 months (range 7-24 months) after treatment of the primary lesion. Statistical Analysis: The statistical analysis of survival was done using the Kaplan-Meier method and the Log Rank test, with p < 0.05 considered to be statistically significant. The Mann-Whitney test and Fisher′s exact test were used for univariate comparison. Results: Twenty-three of the 28 patients had inguinal LND. In group 1, of 13 patients, 12 were alive, with no recurrence of disease at a mean follow-up of 37 months (8-84) months. In group 2, only two patients were alive and disease-free, at a mean follow-up of 58 months (33-84 months). The five-year cancer-specific survival rates for early and delayed LND were 91 and 13%, respectively, (p = 0.007). Conclusions: When compliance with follow-up is suspect, patients with high grade or T stage (greater than T1) tumor are better treated by inguinal LND during the same hospital admission or within two months of primary treatment