RESEARCH ARTICLE

Predicting OncoDX Recurrence Scores With Immunohistochemical Markers: Effect of Stromelysin Scott H. Bradshaw, MD, MSc,* Dale Pidutti,w Denis H. Gravel, MD, FRCPC,* Xinni Song, MD, FRCPC,* and Susan J. Robertson, MD, FRCPC*

Abstract: Recent reports suggest that immunohistochemistry (IHC) markers can be used to give prognostic information in breast cancer that is similar to that contained in the Genomic Health Inc. OncoDX recurrence score (Onco-RS). Our own previous work confirmed that an IHC model based on estrogen receptor (ER), progesterone receptor (PR), and Ki67 predicts 62% of the Onco-RS variability. Other markers used in the Onco-RS include proteins thought to increase tumoral invasive potential, and one such marker is matrix metalloproteinase-11, also called stromelysin 3 (ST3). The goal of this study is to examine the additional value of including ST3 in an IHC-based model that also includes ER, PR, and Ki67 in predicting the Onco-RS, as compared with an IHC model based only on ER, PR, and Ki67 (IHC-RS). The patient population consists of a retrospectively identified cohort of 91 women with ER-positive, HER2neu-negative breast cancer who completed OncoDX testing. Using stepwise multiple regression incorporating Ki67 percentage and semiquantitative ER, PR, and ST3 scores, the ST3 score was not statistically significant. Key Words: oncotype, OncoDX, stromelysin, matrix metalloproteinase, immunohistochemistry, genomic health, recurrence score, breast cancer, Ki67 (Appl Immunohistochem Mol Morphol 2015;23:26–30)

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tage, grade, estrogen receptor (ER), progesterone receptor (PR), and HER2neu status are established prognostic and predictive markers in breast cancer. Many, but not all, low-stage, lymph node (LN)-negative, ER-positive patients have a good prognosis without chemotherapy. Thus, a demand exists for predictive tools to stratify patient risk within this subgroup. The Oncotype DX (OncoDX) test1 is one of the several multigene assays that attempt to fill this gap. This test produces a recurrence score (Onco-RS) validated in prospective

Received for publication October 6, 2013; accepted December 22, 2013. From *The Ottawa Hospital; and wDepartment of Biology, Carleton University, Ottawa, ON, Canada. The authors declare no conflict of interest. Reprints: Scott H. Bradshaw, MD, MSc, Department of Anatomic Pathology and Laboratory Medicine, The Ottawa Hospital-General Campus, Critical Care Wing, 4th Floor, 501 Smyth Road, Ottawa, ON, Canada K1H 8L6 (e-mail: [email protected]). Copyright r 2014 by Lippincott Williams & Wilkins

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clinical studies and for this reason it is publicly funded in Ontario; however, the OncoDX test is expensive. Several genes analyzed in the OncoDX algorithm can be measured by standard immunohistochemistry (IHC). This has led to interest in developing more cost-effective strategies to predict recurrence in LN  ER+ patients.2–9 Previous studies,2,3,9 have shown a correlation between OncoDX score and IHC-based scores. Our own previous work4 confirmed that an IHC model based on ER, PR, and Ki67 predicts 62% of the Onco-RS variability. Other markers used in the Onco-RS include proteins thought to increase tumoral invasive potential, and one such marker is stromelysin 3 (ST3). The present study is designed to assess the value of including ST3 in an IHCbased model that also includes ER, PR, and Ki67 in predicting the Onco-RS, as compared with an IHC model based only on ER, PR, and Ki67 (IHC-RS). As the literature on ST3 in breast cancer is still unclear with respect to the relative importance of stromal versus tumoral source for ST3, measurements that would reflect both were selected.10–13

DESIGN A cohort of 91 women aged 30 to 78 years with ERpositive, HER2neu-negative breast cancer completed OncoDX testing between March 2010 and May 2012. This cohort represents all the patients selected for Oncotype testing during this time interval whose tissue was on file in the central testing laboratory. Additional IHC for ST3 was performed for this cohort, and the data were incorporated into the previously derived4 IHC-RS based on Allred ER score, Allred PR score, and Ki67 percentage.

MATERIALS AND METHODS Prefixation/Ischemic and Total Fixation Time All samples obtained at our institution were sliced and exposed to formalin within 2 hours and total fixation time was held to the ASCAP guidelines of 8 to 72 hours14 with the majority having 24 to 72 hours of fixation time and

Predicting OncoDX recurrence scores with immunohistochemical markers: effect of stromelysin.

Recent reports suggest that immunohistochemistry (IHC) markers can be used to give prognostic information in breast cancer that is similar to that con...
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