Epithelial Paradox: Clinical Significance of Coexpression of E-cadherin and Vimentin With Regard to Invasion and Metastasis of Breast Cancer

Background

E-cadherin and vimentin are regarded as major conventional canonical markers of the epithelial–mesenchymal transition. It is commonly assumed that E-cadherin is uniformly lost during the process of epithelial–mesenchymal transition. Breast tumor cells typically invade as a cohesive multicellular unit in a process called collective invasion. The aim of this study was to reveal the clinical importance of the expression pattern of E-cadherin and vimentin in breast cancer.

Over-expression of EGFR in Breast Cancer

Objective： To explore the relationship of overexpression of epidermal growth factor receptor （EGFR） in occurrence, development and treatment of breast cancer. Methods： Samples of 46 breast adenoma tissues and 86 breast cancer tissues were regularly dehydrate-fixed, embedded in paraffin, sliced in to 5μm thick, stained with SABC immunohistochemistry and coloured with DAB. Results： The positive staining of EGFR was shown as brown- yellow and distributed in cytoplasm. The positive rates in the tissues of breast adenosis and breast cancer were 17.04% （6/46） and 56.98% （49/86） respectively. The positive rates of EGFR in the tissue of invasive ductal carcinoma was 64.49% （41/59）, which was significantly higher than that in in situ carcinoma （P〈0.05）. The positive rate of lymph metastasis group was higher than that in non-lymph metastasis group （P〈0.05）. Conclusion： The overexpression of EGFR was related with occurrence, lymph metastasis and pathologic types of breast cancer. The examination of EGFR in the breast cancer can serve as a guidance for target chemotherapy.     

Clinical outcomes linked to expression of gene subsets for protein hormones and their cognate receptors from LCM-procured breast carcinoma cells

Purpose

Certain peptide hormones and/or their cognate receptors influencing normal cellular pathways also have been detected in breast cancers. The hypothesis is that gene subsets of these regulatory molecules predict risk of breast carcinoma recurrence in patients with primary disease.

Methods

Gene expression levels of 61 hormones and 81 receptors were determined by microarray with LCM-procured carcinoma cells of 247 de-identified biopsies. Univariable and multivariable Cox regressions were determined using expression levels of each hormone/receptor gene, individually or as a pair.

Results

Molecular signatures for ER+/PR+, ER?/PR?, and ER? carcinoma cells deciphered by LASSO were externally validated at HRs (CI) of 2.8 (1.84–4.4), 1.53 (1.01–2.3), and 1.72 (1.15–2.56), respectively. Using LCM-procured breast carcinoma cells, a 16-gene molecular signature was derived for ER+/PR+ biopsies, whereas a 10-gene signature was deciphered for ER?/PR? cancers. Four genes, POMC, CALCR, AVPR1A, and GH1, of this 10-gene signature were identified in a 6-gene molecular signature for ER? specimens.

Conclusions

Applying these signatures, Kaplan–Meier plots definitively identified a cohort of patients with either ER?/PR? or ER? carcinomas that exhibited low risk of recurrence. In contrast, the ER+/PR+ signature identified a cohort of patients with high risk of breast cancer recurrence. Each of the three molecular signatures predicted clinical outcomes of breast cancer patients with greater accuracy than observed with either single-gene analysis or by ER/PR protein content alone. Collectively, our results suggest that gene expression profiles of breast carcinomas with suspected poor prognosis (ER?/PR?) have identified a subset of patients with decreased risk of recurrence.