Research article

Gene expression signatures of morphologically normal breast tissue identify basal-like tumors

Greg Finak^1,2,3 , Svetlana Sadekova^1,4 , Francois Pepin^1,2,3 , Michael Hallett^3,5 , Sarkis Meterissian^6,7 , Fawaz Halwani⁸ , Karim Khetani⁹ , Margarita Souleimanova⁴ , Brent Zabolotny¹⁰ , Atilla Omeroglu⁹ and Morag Park^1,2,4,7,11

¹  Molecular Oncology Group, McGill University Health Centre, 687 Pine Ave, West, H3A 1A1, Quebec, Canada

²  Department of Biochemistry, McGill University, 3655 Promenade Sir William Osler, H3G 1Y6, Montreal, Quebec, Canada

³  McGill Centre for Bioinformatics, McGill University, 3775 University Street, H3A 2B4, Montreal, Quebec, Canada

⁴  Breast Cancer Functional Genomics Group, McGill University, 3775 University Street, H3A 2B4, Montreal, Quebec, Canada

⁵  School of Computer Science, McGill University, 3480 University Street, H3A 2A7, Montreal, Quebec, Canada

⁶  Department of Surgery, McGill University, Montreal, 687 Pine Avenue West, H3A 1A1, Quebec, Canada

⁷  School of Medicine, McGill University, Montreal, 687 Pine Avenue West, H3A 1A1, Quebec, Canada

⁸  Department of Anatomical Pathology, Sunnybrook Health Sciences Center, 2075 Bayview Avenue, M4N 3M5, Ontario, Canada

⁹  School of Pathology, McGill University, 3775 University Street, H3A 2B4, Montreal, Quebec, Canada

¹⁰  Department of Surgery, Grace General Hospital, 300 Booth Drive, R3J 3M7, Winnipeg, Manitoba, Canada

¹¹  Department of Oncology, McGill University, 546 Pine Ave. W, H2W 1S6, Montreal, Quebec, Canada

author email corresponding author email

Breast Cancer Research 2006, 8:R58doi:10.1186/bcr1608

Published:	20 October 2006

Abstract

Introduction

The role of the cellular microenvironment in breast tumorigenesis has become an important research area. However, little is known about gene expression in histologically normal tissue adjacent to breast tumor, if this is influenced by the tumor, and how this compares with non-tumor-bearing breast tissue.

Methods

To address this, we have generated gene expression profiles of morphologically normal epithelial and stromal tissue, isolated using laser capture microdissection, from patients with breast cancer or undergoing breast reduction mammoplasty (n = 44).

Results

Based on this data, we determined that morphologically normal epithelium and stroma exhibited distinct expression profiles, but molecular signatures that distinguished breast reduction tissue from tumor-adjacent normal tissue were absent. Stroma isolated from morphologically normal ducts adjacent to tumor tissue contained two distinct expression profiles that correlated with stromal cellularity, and shared similarities with soft tissue tumors with favorable outcome. Adjacent normal epithelium and stroma from breast cancer patients showed no significant association between expression profiles and standard clinical characteristics, but did cluster ER/PR/HER2-negative breast cancers with basal-like subtype expression profiles with poor prognosis.

Conclusion

Our data reveal that morphologically normal tissue adjacent to breast carcinomas has not undergone significant gene expression changes when compared to breast reduction tissue, and provide an important gene expression dataset for comparative studies of tumor expression profiles.