Sporadic Invasive Breast Carcinomas With Medullary Features Display a Basal-like Phenotype

Breast and Gynecological Cancer Group, Molecular Pathology Programme, Centro Nacional de Investigaciones Oncológicas, Madrid, Spain.
American Journal of Surgical Pathology (Impact Factor: 5.15). 05/2007; 31(4):501-8. DOI: 10.1097/01.pas.0000213427.84245.92
Source: PubMed


It is not clear whether invasive breast carcinomas with medullary features (IBCMFs, atypical medullary carcinomas) constitute a specific phenotype of breast cancer that is of biologic significance. Because medullary features are common in BRCA1-associated carcinomas and these tumors frequently show a basal-like phenotype, we examined whether IBCMFs expressed basal/myoepithelial markers and had a basal-like phenotype. We studied the immunohistochemical expression of 15 markers in tissue microarrays containing samples from 35 IBCMFs and 39 grade 3 invasive ductal carcinomas (IDCG3s) of no special type. In addition, we analyzed EGFR, C-MYC, and CCNE gene amplification by fluorescence in situ hybridization, because the expression of these genes is known to be associated with the basal-like phenotype. We defined the basal-like phenotype according to the criteria of Nielsen et al as being those tumors that were ER/HER2-negative and cytokeratin (CK) 5/6- and/or epidermal growth factor receptor-positive. IBCMFs were more frequently hormone receptor- and HER2-negative, but had greater expression of proliferation markers and p53. In addition, IBCMFs more frequently expressed basal/myoepithelial markers, such as CK5/6 and P-cadherin. A basal-like phenotype was found in 62.9% of IBCMFs but in only 18.9% of IDCG3s. No differences in gene amplification were found between IBCMFs and IDCG3s, although C-MYC amplification was more common in tumors without a basal-like phenotype. The identification of IBCMF as an independent group of tumors could be of clinical significance, given the high incidence of cases with a basal-like phenotype, which is a group of tumors with different prognosis and chemotherapy response from those of IDCG3s of no special type.

13 Reads
  • Source
    • "And previous data add further support to the perception that extensive necrosis is a prognostically unfavorable feature in invasive mammary carcinoma, possibly reflecting a growth rate so rapid that it exceeds tumor sustaining angiogenesis to a substantial degree [21,22]. And the prognostic significance of stromal inflammatory cells within and around invasive duct carcinomas has been the subject of considerable interest and some controversy [23,24]. The reaction consists mainly of mature lymphocytes with a variable admixture of plasma cell, histiocytes, neutrophils, and mast cells. "
    [Show abstract] [Hide abstract]
    ABSTRACT: No clinically useful target molecule has been identified for triple-negative (TN) breast cancer, i.e., estrogen receptor-negative, progesterone receptor-negative, human epidermal growth factor receptor-2-negative phenotype, and its prognosis is poor. The aim of this study is to clarify the clinical and pathologic characteristics of triple negative breast cancer (TNBC). The study subjects, 87 women with TNBC, were a subset of patients operated at Kosin University Gospel Hospital from January 2000 to December 2005. We examined pathologic characteristics such as tumor necrosis, infiltrating border, lymphocytic infiltration, prominent nucleoli in TNBC. And we studied the correlation between TNBC and several factors related to pathologic morphology. Chi-squared tests were used for statistical analysis. Kaplan-Meier estimates are presented for the survival function, and differences in survival were analyzed using the log rank test. Tumor necrosis was found in 51 patients (58.3%) in TNBC. And infiltrating border was found in 71 patients (81.0%). Also continuous lymphocytic distribution and prominent nucleoli was found in 31 patients (35.7%), 52 patients (59.7%), respectively. No association was detected between pathologic characteristics and other biological markers. Patients with tumor necrosis positive for TNBC didn't show shorter disease-free survival (P = 0.4490) or overall survival (P = 0.979) than patients without tumor necrosis. These findings suggest that pathologic characteristics cannot be used to classify triple-negative breast cancer into only two subtypes with differing prognoses. But because our study is small size study, more abundant patients' dates will be needed to evaluate the morphologic characteristics' predictive role.
    Full-text · Article · May 2011
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Advances in the analysis of expression profiles, using genomic techniques, have revealed the high heterogeneity present in breast cancers. These approaches have served to identify different breast cancer subgroups with specific molecular characteristics that could sub-classify these tumours as carcinomas expressing hormone receptors, denominated Luminal subtype, and tumours with negative expression of hormone receptors, the Basal and HER2+ phenotypes. Therefore, during recent years, identification of markers characteristic of each subtype has been the focus of many research groups. All of these breast tumour subtypes probably have specific clinical and morphological features; however, this hypothesis needs to be confirmed by analysing more homogenous series. Although this “new” classification has limitations, it could be useful in the clinical practice, allowing not only a more accurate prognosis in breast cancer patients but also a selective treatment for each predefined subtype.
    Full-text · Article · Dec 2008 · Clinical and Translational Oncology
  • [Show abstract] [Hide abstract]
    ABSTRACT: Breast cancers arising in carriers of germline BRCA1 mutations frequently have a basal-like phenotype. Basal-like cancers are characterized by high histological grade, central necrotic areas, foci with metaplastic differentiation, lack of hormone receptor and HER2 (ErbB2) expression, and consistent positivity for basal markers, including CK5/6, CK14, and EGFR. We have used germline manipulation to generate a conditional mouse model of Brca1 deficiency. Transgenic expression of Cre recombinase in the mammary gland of these mice results in deletion of exons encoding the C-terminus of Brca1 and leads to tumour formation when combined with heterozygosity for a p53 mutation. Histologically, these mammary gland tumours were characterized by high histological grade, central necrotic areas, and presence of homologous metaplastic elements. These metaplastic elements consisted of neoplastic spindle cells or squamous cell differentiation in the form of keratin pearls or individual cell keratinization. Immunohistochemical analysis revealed expression of basal-like markers in all cases. The tumour phenotype generated in our mouse model was compared with published data on human basal-like breast carcinomas and also with metaplastic breast cancers with a basal-like phenotype; the comparison showed that we have generated a mouse model of basal-like breast cancer, which should prove useful in testing new and targeted treatments for this type of breast cancer.
    No preview · Article · Mar 2007 · The Journal of Pathology
Show more