Correlation of micro vessel density [MVD] and proliferation index [PI] with clinico-pathological parameters in breast carcinoma

Background: One of the greatest challenges in breast cancer management is to accurately predict the outcome for each patient. Microvessel density [MVD] correlated closely with increasing number of tumor cells shed into the bloodstream and development of metastasis. Because proliferation status closely correlates with tumor aggressiveness, proliferation index [PI] is considered as an established prognostic marker for various tumors. We aimed to: 1. Study WVD and PI by assessing immunohistochemical profiles of CD31 and Ki67 respectively and their probable role in breast cancer progression. 2. Assess values of CD31 and Ki67 in relations to clinico-pathological prognostic parameters

Subjects and methods: Immunostaining was done to detect CD31 and Ki67 expressions in 74 specimens of breast lesions

Results: Both CD31 and Ki67 increased progressively along the continuum of neoplastic changes from normal breast epithelium to invasive ductal carcinomas; IDC [P<0.000 for each]. CD31 expression was positively correlated with minor size [p< 0.04], increasing grade [P<0.01], lymphovascular invasion [p<0.01] and lymph node metastasis [P< 0.05] in IDC. There was significant positive correlation between Ki67 expression and increasing grade [P<0.03] and lymph node metastasis [P<0.02] in IDC. Positive correlation was present between Ki67 and CD31 in ductal carcinoma in situ [DCIS] and in IDC [P<0.02 and P<0.001 respectively]

Conclusion: Our findings indicate that aggressive tumors are more capable of angiogenesis and proliferation which are poor prognostic signs in IDC. These findings might open the door for new therapeutic strategies to prevent progression of DCIS to IDC

Association of Leu125Val polymorphism of platelet endothelial cell adhesion molecule-1 (PECAM-1) gene & soluble level of PECAM-1 with coronary artery disease in Asian Indians.

BACKGROUND & OBJECTIVES: Platelet endothelial cell adhesion molecule-1 (PECAM-1) plays a key role in the transendothelial migration of circulating leukocytes (diapedesis) during vascular inflammation. We hypothesized that genetic variation and the level of soluble PECAM-1 could be associated with the development of atherosclerosis and conducted a study on gene polymorphisms of PECAM-1 and soluble PECAM-1 levels in Asian Indian patients with coronary artery disease (CAD) in Singapore. METHODS: Of the 137 angiographically confirmed patients (> or =70% stenosis) of CAD and 110 controls in Asian Indian population, two single nucleotide polymorphisms (SNPs) of PECAM-1 gene, C+373G (Leu125Val) at exon 3 and G+1688A (Ser563Asn) at exon 8 were analyzed by polymerase chain reaction-restriction fragment-length polymorphism (PCR-RFLP) strategy. In addition, plasma soluble PECAM-1, P-selection and lipid profile were measured. Chi- square test and student t test were adopted to compare categorical and continuous variables, respectively. RESULTS: A significant decrease in C allele frequency but increase in G allele frequency of the Leu125Val (C/G) polymorphism were observed in CAD patients as compared with controls (0.54/0.46 vs 0.663/0.337 respectively, P=0.008). Alteration in genotype distributions (CC, CG and GG) of the Leu125Val polymorphism between CAD patients and controls (P=0.009) was also significant. A similar trend was observed on the allele frequencies (G/A) and genotype distributions of Ser563Asn (G/A) polymorphism, though the difference did not reach significance. On the other hand, plasma level of soluble PECAM-1 (sPECAM-1) was markedly elevated in CAD patients (P=0.006), and associated with soluble P-selectin and lipid profiles. INTERPRETATION & CONCLUSION: Our study showed that Leu125Val polymorphism of PECAM-1 gene and elevated soluble PECAM-1 were related to severe coronary artery stenosis in CAD patients of Asian Indian origin in Singapore. Our data also suggest that PECAM-1 plays an important role in the development of atherosclerosis.