Erratum to: Elafin is downregulated during breast and ovarian tumorigenesis but its residual expression predicts recurrence.

Joseph A Caruso,Khandan Keyomarsi,Aysegul Sahin,Melissa Bondy,Constance Albarracin,Kelly K Hunt,Min Yi,Jinsong Liu,Jing Zhang,Cansu Karakas

doi:10.1186/s13058-015-0572-5

Abstract

Elafin is an endogenous serine protease inhibitor. The majority of breast cancer cell lines lack elafin expression compared to human mammary epithelial cells. In this study, we hypothesized that elafin is downregulated during breast and ovarian tumorigenesis. We examined elafin expression by immunohistochemistry (IHC) in specimens of normal breast tissue (n = 24), ductal carcinoma in situ (DCIS) (n = 54), and invasive breast cancer (n = 793). IHC analysis of elafin expression was also performed in normal fallopian tube tissue (n = 20), ovarian cystadenomas (n = 9), borderline ovarian tumors (n = 21), and invasive ovarian carcinomas (n = 216). To understand the significance of elafin in luminal breast cancer cell lines, wild-type or M25G elafin (lacking the protease inhibitory function) were exogenously expressed in MCF-7 and T47D cells. Elafin expression was downregulated in 24% of DCIS and 83% of invasive breast tumors when compared to elafin expression in the normal mammary epithelium. However, the presence of elafin-positive cells in invasive breast tumors, even at low frequency, correlated with poor recurrence-free survival (RFS), reduced overall survival (OS), and clinicopathological markers of aggressive tumor behavior. Elafin-positive cells were an especially strong and independent prognostic marker of reduced RFS in IHC-defined luminal A-like tumors. Elafin was also downregulated in 33% of ovarian cystadenomas, 43% of borderline ovarian tumors, and 86% of invasive ovarian carcinomas when compared to elafin expression in the normal fallopian tube. In ovarian tumors, elafin-positive cells were correlated with reduced RFS, OS and disease-specific survival (DSS) only in stage I/II patients and not in stage III/IV patients. Notably, exogenous expression of elafin or elafin M25G in the luminal breast cancer cell lines MCF-7 and T47D significantly decreased cell proliferation in a protease inhibitory domain-independent manner. Elafin predicts poor outcome in breast and ovarian cancer patients and delineates a subset of endocrine receptor-positive breast cancer patients susceptible to recurrence who could benefit from more aggressive intervention. Our in vitro results suggest that elafin arrests luminal breast cancer cells, perhaps suggesting a role in tumor dormancy.

Highlights

Erratum During the editorial process preceding the publication of this article an error was introduced in the heading of “Table 1 Univariate and multivariate analysis of elafinpositive cells in breast cancer patients.” This error was only noticed after publication of the final version
Caruso JA, Karakas C, Zhang J, Yi M, Albarracin C, Sahin A, et al Elafin is downregulated during breast and ovarian tumorigenesis but its residual expression predicts recurrence
* Correspondence: kkeyomar@mdanderson.org 1Department of Experimental Radiation Oncology, University of Texas at MD Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX 77030, USA 5The University of Texas Graduate School of Biomedical Sciences, 6767 Bertner Ave, Houston, Texas 77030, USA Full list of author information is available at the end of the article

Summary

Introduction

Erratum During the editorial process preceding the publication of this article an error was introduced in the heading of “Table 1 Univariate and multivariate analysis of elafinpositive cells in breast cancer patients.” This error was only noticed after publication of the final version. Author details 1Department of Experimental Radiation Oncology, University of Texas at MD Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX 77030, USA. Duncan Cancer Center, 1 Baylor Plaza, Houston, Texas 77030, USA.

Results

Conclusion