title: Negative/low HER2 expression alone or combined with E-cadherin positivity is predictive of better prognosis in patients with breast carcinoma.
abstract: The loss of E-cadherin expression leads to absence of tissue integrity, an essential step in tumor progression. Methylation of CpG islands in the promoter region of the CDH1 gene coding E-cadherin might be an alternative for gene silencing. In the present study, we investigate the expression of E-cadherin and hormone receptors in invasive ductal breast carcinoma (IDCs). Protein expression was analysed immunohistochemically in 87 cases, including 26 familial tumors. The most interesting results revealed a significantly reduced E-cadherin expression in cases with familial history compared to sporadic tumors (p=0.009), as well as with tumors ≤5 cm (p=0.022). Moreover, HER2 over-expression was associated with distant metastasis (p=0.011) and overall survival (p log rank=0.028). Tumors displaying negative/low HER2 expression combined with E-cadherin positivity confer better patient survival (p=0.052). Triple Negative tumors (TN) were more frequently found in patients with advanced grade (GIII) (p=0.001) and TNM (III+IV) (p=0.018) which supports the aggressive behavior of TN tumors. On the other hand, hypermethylation of CDH1 gene promoter was observed in 46% of hereditary cases and strongly associated with loss of E-cadherin expression (p=0.002). Furthermore, patients with unmethylated CDH1 pattern have a better 5-year disease free survival (p=0.021). In conclusion, in patients with hereditary breast cancer, the CpG methylation event contributes to the loss of E-cadherin expression. On the other hand, HER2 over-expression is predictive of worse prognosis, either alone or combined with loss of E-cadherin expression in Tunisian patients with breast cancer.
authors.affiliation: Laboratory of Biomass Valorization and Production of Eukaryotic proteins Center of Biotechnology of Sfax BP K Sfax. University of Sfax, Tunisia.
authors.forename: Sondes
authors.initials: S
authors.lastname: Karray-Chouayekh
authors.forename: Fatma
authors.initials: F
authors.lastname: Trifa
authors.forename: Abdelmajid
authors.initials: A
authors.lastname: Khabir
authors.forename: Tahia
authors.initials: T
authors.lastname: Sellami-Boudawara
authors.forename: Mounir
authors.initials: M
authors.lastname: Frikha
authors.forename: Ali
authors.initials: A
authors.lastname: Gargouri
authors.forename: Raja
authors.initials: R
authors.lastname: Mokdad-Gargouri
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015703:Antigens, CD; D014408:Biomarkers, Tumor / Q000032:analysis* / Q000235:genetics; D001943:Breast Neoplasms / Q000737:chemistry* / Q000235:genetics / Q000401:mortality / Q000473:pathology / Q000628:therapy; D015820:Cadherins / Q000032:analysis* / Q000235:genetics; D018270:Carcinoma, Ductal, Breast / Q000737:chemistry* / Q000235:genetics / Q000401:mortality / Q000556:secondary / Q000628:therapy; D016009:Chi-Square Distribution; D019175:DNA Methylation; D018572:Disease-Free Survival; D005260:Female; D020022:Genetic Predisposition to Disease; D040941:Heredity; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008875:Middle Aged; D060787:Neoplasm Grading; D010641:Phenotype; D011237:Predictive Value of Tests; D011379:Prognosis; D011401:Promoter Regions, Genetic; D016016:Proportional Hazards Models; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis*; D011960:Receptors, Estrogen / Q000032:analysis; D011980:Receptors, Progesterone / Q000032:analysis; D013997:Time Factors; D014416:Tunisia
chemical_list: D015703:Antigens, CD; D014408:Biomarkers, Tumor; D015820:Cadherins; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; C513384:CDH1 protein, human; C508053:ERBB2 protein, human