J Breast Cancer.  2009 Mar;12(1):4-13. 10.4048/jbc.2009.12.1.4.

Prognostic Significance of Basal Markers in Triple-negative Breast Cancers

• Kim JM
• Hwang TY
• Kang SH
• Lee SJ
• Bae YK

• KMID: 2286572
• DOI: http://doi.org/10.4048/jbc.2009.12.1.4

Abstract

PURPOSE: We have investigated the prognostic significance of the expression of basal markers for triple-negative (estrogen receptor-negative, progesterone receptor-negative and human epidermal growth factor receptor-2-negative) breast cancers (TNBCs).
METHODS
An immunohistochemical study was performed on tissue microarrays constructed with 643 invasive breast carcinoma samples. We subclassified the TNBCs into basal phenotype (BP) and non-BP groups by the use of four different criteria according to the immunprofiles for cytokeratin5/6 (CK5/6), epidermal growth factor receptor (EGFR), vimentin, c-Kit, p63 and P-cadherin. The criteria consisted of criterion 1: CK5/6+ only, criterion 2: CK5/6+ and/or EGFR+, criterion 3: CK5/6+ and/or EGFR+ and/or vimentin+ and criterion 4: one or more marker(s) positive among the six basal markers. Each of these criteria, as well as the status of each individual marker, was evaluated to estimate prognosis for TNBC patients.
RESULTS
Of the breast carcinomas, 165 cases (25.7%) were TNBCs. As compared with the non-TNBCs, TNBCs were associated with a larger tumor size (p=0.001), higher histological grade (p<0.001) and shorter overall survival (OS) (p=0.002) and disease-free survival (DFS) (p=0.05). Lymph node status, tumor size and expression of EGFR or c-Kit were independent prognostic factors for patients with TNBC. As compared with the non-BP, BP as defined by criterion 2 was an independent poor prognostic factor for OS and DFS among patients with a lymph node metastasis (p=0.044 and p=0.01) and among patients who received anthracycline-based adjuvant chemotherapy (p=0.009 and p=0.01, respectively).
CONCLUSION
Patients with TNBCs showed a poorer prognosis as compared to patients with non-TNBCs. Selected group of the basal-like breast cancers (BLBCs) defined by the immunohistochemical profiles of basal markers showed survival differences from non-BLBCs in subgroups of TNBCs with a homogeneous clinical finding.

Keyword

Basal-like breast cancer; Breast cancer; Immunohistochemistry; Prognosis; Triple-negative breast cancer

MeSH Terms

Breast
Breast Neoplasms
Cadherins
Chemotherapy, Adjuvant
Disease-Free Survival
Epidermal Growth Factor
Humans
Immunohistochemistry
Lymph Nodes
Neoplasm Metastasis
Phenotype
Progesterone
Prognosis
Receptor, Epidermal Growth Factor
Vimentin
Cadherins
Epidermal Growth Factor
Progesterone
Receptor, Epidermal Growth Factor
Vimentin

Figure

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  Figure 1 Kaplan-Meier survival curves of patients with TNBCs (n=165) and non-TNBCs (n=478). Patients with a TNBC had significantly reduced OS compared to those with a non-TNBC, especially within the first 6 yr. TNBC=triple negative breast cancer; OS=overall survival.

• 

  Figure 2 Representative immunohistochemical results. Some tumors showed strong and diffuse, cytoplasmic or membranous staining for (A) cytokeratin5/6 and (B) EGFR. (C) Vimentin was expressed in both tumor cells and stroma cells in some cases. (D) c-Kit immunoreactivity was observed in tumor cell cytoplasm. (E) p63 immunostaining was observed in tumor cell nuclei in a minority of cases. (F) P-cadherin immunoreactivity was characterized by strong membranous staining. Original magnification, ×200. EGFR=epidermal growth factor receptor.

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