CD3+, CD4+ & CD8+ tumour infiltrating lymphocytes (TILs) are predictors of favourable survival outcome in infiltrating ductal carcinoma of breast.

Background & objectives: Tumour infiltrating lymphocytes (TILs) represent the host immune response against cancer cells associated with good or bad prognosis in different tumour types. This study was undertaken to evaluate the significance of CD3+, CD4+ and CD8+ TILs in breast cancer tissues in relation to clinico-pathological variables and survival outcome. Methods: Immunohistochemistry (IHC) was performed with antibodies against CD3, CD4 and CD8 antigens on formalin-fixed paraffin-embedded tissue sections of 150 breast cancer patients. Intratumoural and stromal TIL counting was performed semiquantitatively. Results: The higher CD3+, CD4+ and CD8+ intratumoural and stromal counts showed independent and direct association with good prognosis. The prognostic predictor value of intratumoural counts was higher than stromal counts. The independent associations of intratumoural and stromal counts became more prominent when adjusted with stage and grade, respectively. Among intratumoural counts, the high (++/+++) CD4+ count (OR=3.85, 95% CI=3.28-16.71, P<0.001) showed the highest survival followed by CD3+ (OR=2.70, 95% CI=1.76-8.30, P=0.001) and CD8+ (OR=2.58, 95% CI=1.55-5.86, pP=0.001) the least when compared to respective low (+) counts. In contrast, among stromal counts, the high CD8+ count (OR=3.13, 95% CI=2.20-9.57, pP<0.001) showed the highest survival followed by CD4+ (OR=3.02, 95% CI=2.07-8.89, 0.001) and CD3+ (OR=2.45, 95% CI=1.53-6.73, 0.002) the least. Interpretation & conclusions: Our results suggest that intratumoural CD4+ and stromal CD8+ counts by immunohistochemistry may serve as an independent prognosticator for favourable outcome in breast cancer.

Vitamin D receptor (FokI, BsmI and TaqI) gene polymorphisms and type 2 diabetes mellitus : A North Indian study.

Background : The vitamin D receptor (VDR) gene is a candidate gene for susceptibility to several diseases. Studies on association between VDR polymorphisms and risk of type 2 diabetes (T2DM) in different ethnic populations are yet inconclusive. Aims : This study was conducted to evaluate association between VDR polymorphisms and genetic susceptibility to T2DM in the north Indian population. Settings and Design : One hundred clinically diagnosed T2DM patients and 160 healthy controls from the north Indian population were recruited for genetic association study. Materials and Methods : Genomic DNA was extracted from blood and genotyped for the single nucleotide polymorphism SNPs of FokI (T/C) [rs2228570], BsmI (A/G) [rs1544410] and TaqI (C/T) [rs731236] by polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP) analysis. Statistical Analysis Used : Genotype distribution and allelic frequencies were compared between patients and controls. Mean values and odds ratios (ORs) with 95% confidence interval (CI) were calculated using SPSS software (version 15.0). Results : The genotype distribution, allele and haplotype frequencies of VDR polymorphism did not differ significantly between patients and controls. Mean age and waist-hip ratio of patients were found to be associated with VDR polymorphism. Combination studies showed FFBbtt increased the risk of T2DM in north Indians. Conclusions : Our data suggest that VDR gene polymorphism in combination of genotypes is associated with the risk of T2DM and thus requires further studies as a probable genetic risk marker for T2DM.

Association of IL-4 and IL-1RN (receptor antagonist) gene variants and the risk of type 2 diabetes mellitus: A study in the north Indian population.

Background: Inflammation is a key event closely associated with the pathophysiology of type 2 diabetes mellitus (T2DM). Association of genetic polymorphisms of inflammatory cytokines with T2DM is largely unknown. Our objective was to investigate the relationship of polymorphism of IL-1RN and IL-4, two important biomarkers of inflammation, with the risk of T2DM. Setting and Design: We recruited 120 clinically diagnosed T2DM patients and 150 normal healthy controls for this study in order to evaluate the nature of polymorphisms of IL-1RN and IL-4. Materials and Methods: Genomic DNA was isolated from the blood of all subjects, and the variable number of tandem repeat (VNTR) polymorphisms of IL-1RN and IL-4 genes was identified by polymerase chain reaction. Statistical Analysis Used: Genotype distribution and allelic frequencies were compared between patients and control group. Means, as well as odds ratios (ORs) with 95% confidence intervals (CI), were calculated using SPSS software (version 11.5). Results: Our study revealed that distribution of both IL-4 and IL-1RN (VNTR) gene polymorphisms were significantly associated with T2DM subjects. We, however, failed to find any association of gene-gene (IL-4 and IL-1RN) interaction with T2DM. Conclusions: Both IL-4 and IL-1RN (VNTR) gene polymorphisms were significantly associated with T2DM subjects. This may suggest that the genetic polymorphisms of IL-4 and IL-1RN genes could serve as susceptibility indicators for T2DM in the Indian population, but the actual mechanism of these associations will require more elaborate investigations. Lack of association of gene-gene (IL-4 and IL-1RN) interaction with T2DM may indicate the independent nature of influence of both these genes on the risk of T2DM.