MYC is expressed in the stromal and epithelial cells of primary breast carcinoma and paired nodal metastases

Mundim,Fiorita  Gonzales Lopes; Pasini,Fatima  Solange; Brentani,Maria  Mitzi; Soares,Fernando  Augusto; Nonogaki,Suely; Waitzberg,Angela  Flávia Logullo

doi:10.3892/mco.2015.526

MYC is expressed in the stromal and epithelial cells of primary breast carcinoma and paired nodal metastases

Authors:
- Fiorita Gonzales Lopes Mundim
- Fatima Solange Pasini
- Maria Mitzi Brentani
- Fernando Augusto Soares
- Suely Nonogaki
- Angela Flávia Logullo Waitzberg
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Affiliations: Department of Pathology, Federal University of São Paulo, São Paulo, SP 04023-900, Brazil, Department of Radiology and Oncology (LIM24), Medical School of São Paulo University, São Paulo, SP 01246‑903, Brazil, Department of Pathology, A.C. Camargo Hospital, São Paulo, SP 01509-010, Brazil
Published online on: March 6, 2015 https://doi.org/10.3892/mco.2015.526
Pages: 506-514
Copyright: © Mundim et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

The MYC oncogene is directly involved in the proliferation, metabolism, progression and distant metastasis of breast cancer. Since metastatic spread to the lymph nodes is often the first indication of propensity for metastatic dissemination, the MYC status in nodal disease may represent a decision‑making variable. However, the analysis of MYC expression in stromal cells, namely cancer‑associated fibroblasts (CAFs), which are known to play a critical role in cancer progression, remains poorly reported. The aim of this study was to determine the expression of MYC and other markers, including estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), p53, Ki67, epidermal growth factor receptor (EGFR), phosphorylated AKT (p‑AKT) and phospho‑mammalian target of rapamycin (p‑mTOR) by immunohistochemistry in representative samples from 80 patients with ductal infiltrative breast cancer and 43 paired compromised axillary lymph nodes allocated in tissue microarrays (TMAs). The epithelial and stromal components of primary tumors and respective lymph node metastases were separately analyzed. MYC expression (cytoplasmic and nuclear) was a frequent event in the epithelial and stromal components of the primary tumors. The epithelial cells in the nodal metastases exhibited a trend for decreased MYC expression compared to that in the primary tumors (p=0.08) but retained the original status of the primary tumors for all other markers. The stromal cells were uniformly negative for ER, PR, HER2, p53, Ki67 and EGFR. Comparison of the stromas of primary tumors and respective lymph node metastases revealed a reduced frequency of nuclear MYC in 15% of the cases (p=0.003), whereas p‑mTOR followed a similar trend (p=0.09). Analyses of the possible correlations among markers revealed that epithelial nuclear MYC was associated with p53 (p=0.048). This is an original study demonstrating a significant proportion of MYC expression (nuclear or cytoplasmic), as well p‑mTOR and p‑AKT expression, in the epithelial and stromal components of either the primary tumor or the nodal metastases. CAFs expressing MYC may establish an angiogenic microenvironment supporting cancer survival and facilitating colonization at the nodal metastatic site.

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