Cyclin D1 overexpression in Algerian breast cancer women: correlation with CCND1 amplification and clinicopathological parameters.

BACKGROUND: Cyclin D1 which is associated with cell cycle regulation is solidly established as an oncogene with an important pathogenetic role in breast carcinomas. OBJECTIVES: The aim of this study was to relate the Cyclin D1 protein overexpression with the amplification of its gene CCND1 in Estrogen Receptors (ER) positive breast carcinomas, in order to investigate the prognostic effect of their aberrations in relation to ER status, also to correlate the Cyclin D1 overexpression with other prognostic parameters. MATERIALS AND METHODS: Chromogenic in situ hybridization (CISH) was used to identify CCND1 amplification on formalin-fixed paraffin-embedded invasive ductal carcinoma, in which immunohistochemistry (IHC) had previously been performed in order to evaluate the pathological relevance of Cyclin D1 overexpression in human breast cancer (n = 138). RESULTS: CCND1 amplification was identified in 17/138 (12.3%) tumors and 78/138 (56.5%) tumors have overexpressed Cyclin D1. A significant correlation was identified between CCND1 amplification and Cyclin D1 overexpression (P < 0.001) and both Cyclin D1 and CCND1 were related with ER expression. CONCLUSION: Our results show a significant correlation between Cyclin D1 overexpression and CCND1 amplification. Overexpression of Cyclin D1was observed in high proportion of breast cancer which should be considered for routine diagnosis.

BRCA1 and BRCA2 Germline Mutation Screening in Western Algeria using High Resolution Melting Analysis (HRM).

Breast cancer is the leading cause of cancer deaths in Algerian women. Our aim is to analyze BRCA1 and BRCA2 genes mutations in 100 Algerian patients with a family history suggestive of genetic predisposition to breast cancer. BRCA1 and BRCA2 mutations were searched by High-Resolution Melting (HRM) analysis, followed by direct sequencing, and Multiplex Ligation- Dependent Probe Amplification (MLPA) for large deletions or duplications. An unclassified variant c.5117G>C, p.Gly1706ALA and a pathogenic mutation c.2125_2126insA, p.Phe709TyrfX3 were detected in the BRCA1 gene. No large deletions or duplications were detected with MLPA. One deleterious mutation c.250C>T, p.Gin84X, and one unclassified variant c.9364G>A, p. Ala3122Thr were identified in BRCA2 gene. The pathological significance of this variant has to be specified and analysis of its segregation in the family and differs from those provided in the literature. Although on a limited cohort, our findings suggest a higher frequency of BRCA1/2 mutations in Algeria and it would be of interest to search for the presence of these pathogenic mutations in other family member for preventing the risk of cancer.