J Breast Cancer.  2017 Mar;20(1):45-53. 10.4048/jbc.2017.20.1.45.

Clinicopathologic and Prognostic Significance of Transducin-Like Enhancer of Split 1 Protein Expression in Invasive Breast Cancer

• Lee JH
• Bae SB
• Oh MH
• Cho HD
• Jang SH
• Hong SA
• Cho J
• Kim SY
• Han SW
• Lee JE
• Kim HJ
• Lee HJ

• KMID: 2379398
• DOI: http://doi.org/10.4048/jbc.2017.20.1.45

Abstract

PURPOSE
Transducin-like enhancer of split 1 (TLE1) is a member of the TLE family of transcriptional co-repressors that control the transcription of a wide range of genes. We investigated the prognostic significance of TLE1 protein expression in breast cancers by using immunohistochemistry and explored the relationship of TLE1 with clinicopathological parameters.
METHODS
Immunohistochemistry was performed on 456 cases of breast cancer tiled on tissue microarrays. The relationship between TLE1 expression in normal breast specimens and ductal carcinoma in situ (DCIS) was also analyzed.
RESULTS
TLE1 was highly expressed in 57 of 456 (12.5%) carcinoma samples. TLE1 was more frequently expressed in DCIS and invasive breast cancers than in normal breast tissue (p=0.002). High expression of TLE1 significantly correlated with negative lymph node (LN) metastasis (p=0.007), high histologic grade (p<0.001), estrogen receptor negativity (p<0.001), progesterone receptor negativity (p<0.001), human epidermal growth factor receptor 2 (HER2) positivity (p<0.001), and high Ki-67 proliferation index (p<0.001). Based on intrinsic subtypes, high TLE1 expression was strongly associated with HER2+ and triple-negative breast cancers (TNBC) (p<0.001). Survival analysis demonstrated no significant association between TLE1 expression and disease-free survival (DFS) (p=0.167) or overall survival (OS) (p=0.286). In subgroup analyses, no correlation was found between TLE1 expression and DFS or OS according to LN status or intrinsic subtype.
CONCLUSION
High TLE1 expression is significantly associated with the HER2+ and TNBC subtypes. This is the first study documenting immunohistochemical expression of TLE1 in invasive breast cancer and its association with clinicopathological parameters, prognosis, and intrinsic subtype.

Keyword

Breast neoplasms; Immunohistochemistry; Prognosis; TLE1 protein; human

MeSH Terms

Breast Neoplasms*
Breast*
Carcinoma, Intraductal, Noninfiltrating
Co-Repressor Proteins
Disease-Free Survival
Estrogens
Humans
Immunohistochemistry
Lymph Nodes
Neoplasm Metastasis
Prognosis
Receptor, Epidermal Growth Factor
Receptors, Progesterone
Triple Negative Breast Neoplasms
Co-Repressor Proteins
Estrogens
Receptor, Epidermal Growth Factor
Receptors, Progesterone

Figure

• 

  Figure 1 Immunohistochemical expression of transducin-like enhancer of split 1 (TLE1) in breast cancer: (A) score 0, no staining or staining in <1% of the tumor cells; (B) score 1, weak or staining in 1% to 10% of the cells; (C) score 2, moderate or staining in 11% to 50% of the cells; and (D) score 3, strong or staining in >50% of tumor cells. TLE1 expressed in nuclei of the tumor cells (original magnification, ×200).

• 

  Figure 2 Average staining intensity of transducin-like enhancer of split 1 expression was significantly higher in malignant tumors than in normal breast tissues. Normal=normal breast tissue; DCIS=ductal carcinoma in situ; IBC= invasive breast carcinoma.

• 

  Figure 3 Kaplan-Meier survival curves for transducin-like enhancer of split 1 (TLE1)-high and TLE1-low breast cancer patients. TLE1-high breast cancer patients in all cases, in lymph node (LN) (−) group, and in LN (+) group have no longer disease-free survival (A, C, and E) and overall survival (B, D, and F) compared to patients with TLE1-low expression.

• 

  Figure 4 Kaplan-Meier survival curves for transducin-like enhancer of split 1 (TLE1)-high and TLE1-low according to the intrinsic subtype. TLE1-high luminal A, luminal B, human epidermal growth factor receptor 2 (HER2) type, and triple-negative breast cancer (TNBC) breast cancer patients have no longer disease-free survival (A, C, E, and G) and overall survival (B, D, F, and H) compared to patients with TLE1-low expression.

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