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Differences and Molecular Immunohistochemical Parameters in the Subtypes of Infiltrating Ductal Breast Cancer

Cristina Bertolo PhD, David Guerrero PhD, Francisco Vicente MD, PhD, Alicia Cordoba MD, PhD, Manel Esteller MD, PhD, Santiago Ropero PhD, Francisco Guillen-Grima MD, MPH, MSc, PhD, Jose Maria Martinez-Peñuela MD, PhD, Jose Miguel Lera MD, PhD
DOI: http://dx.doi.org/10.1309/J3QV9763DYPV338D 414-424 First published online: 1 September 2008


Breast cancer is a heterogeneous disease, and patients are categorized into subtypes according to gene expression. We studied the associations among molecular, immunohistochemical, and clinicopathologic features and their distribution according to the subtypes luminal, HER2, basal, and normal-like in 60 patients with invasive ductal breast carcinoma without distant metastasis at the time of diagnosis (M0). We evaluated the hypermethylation of the CDH-1, RASSF1A, SIAH-1 and TSLC-1 genes by methylation-specific polymerase chain reaction and the expression of p53, bcl-2, cyclin D1, E-cadherin, and β-catenin proteins in tissue microarrays by immunohistochemical analysis. Expression of bcl-2 was associated with the luminal subtype (P = .003), and CDH-1 hypermethylation was present preferentially in HER2 tumors (P = .038). The basal subtype was characterized by the expression of β-catenin (P = .003). The hypermethylation of CDH-1 and the expression of bcl-2, cyclin D1, and β-catenin proteins differ among breast cancer subtypes.

Key Words:
  • Breast cancer subtypes
  • Hypermethylation
  • Prognosis
  • Tissue microarray
  • Tumor markers