Low CD10 mRNA Expression Identifies High-Risk Ductal Carcinoma In Situ (DCIS)

Jérôme Toussaint,Marianne Paesmans,Valérie Doriath,Benjamin Haibe-Kains,Martine Piccart,Christos Sotiriou,Sevilay Altintas,Philippe Bedard,Wiebren A Tjalma,Denis Larsimont,Virginie Durbecq,Ghizlane Rouas

doi:10.1371/journal.pone.0012100

Jérôme Toussaint, Marianne Paesmans + Show 10 more

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https://doi.org/10.1371/journal.pone.0012100

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Journal: PloS one	Publication Date: Aug 10, 2010
Citations: 33	License type: CC BY 4.0

Affiliation: Institut Jules Bordet, Antwerp University Hospital

Abstract

PurposeOptimal management of breast ductal carcinoma in situ (DCIS) is controversial, and many patients are still overtreated. The local death of myoepithelial cells (MECs) is believed to be a pre-requisite to tumor invasion. We thus hypothesized that loss of CD10 expression, a MEC surface peptidase, would signify basement membrane disruption and confer increased risk of relapse in DCIS. The aim of our study was to retrospectively evaluate the prognostic value of CD10 in DCIS.Experimental DesignCD10 expression was evaluated by quantitative RT-PCR and immunohistochemistry using paraffin-embedded samples of normal breast tissue (n = 11); of morphologically normal ducts associated with DCIS (n = 10); and of DCIS without an invasive component (n = 154).ResultsCD10 immunostaining was only observed in MECs in normal tissue and in DCIS. Normal tissue showed high mRNA expression levels of CD10, whereas DCIS showed a variable range. After a median follow-up of 6 years, DCIS with CD10 expression below the levels observed in normal tissue (71%) demonstrated a higher risk of local relapse (HR = 1.88; [95CI:1.30–2.70], p = 0.001) in univariate analysis. No relapse was observed in patients expressing high CD10 mRNA levels (29%) similar to the ones observed in normal tissue. In multivariate analysis including known prognostic factors, low CD10 mRNA expression remained significant (HR = 2.25; [95%CI:1.24–4.09], p = 0.008), as did the recently revised Van Nuys Prognostic Index (VNPI) score (HR = 2.03; [95%CI:1.23–3.35], p = 0.006).ConclusionThe decrease of CD10 expression in MECs is associated with a higher risk of relapse in DCIS; this knowledge has the potential to improve DCIS management.

Highlights

With the widespread use of high quality screening mammography, the incidence of ductal carcinoma in situ (DCIS) has increased dramatically
After a median follow-up of 6 years, DCIS with CD10 expression below the levels observed in normal tissue (71%) demonstrated a higher risk of local relapse (HR = 1.88; [95CI:1.30–2.70], p = 0.001) in univariate analysis
No relapse was observed in patients expressing high CD10 mRNA levels (29%) similar to the ones observed in normal tissue

Summary

Introduction

With the widespread use of high quality screening mammography, the incidence of ductal carcinoma in situ (DCIS) has increased dramatically. DCIS accounts for approximately 20% of all screening-detected breast cancer [1]. DCIS is pathologically described as the proliferation of malignant epithelial cells that have not invaded beyond the basement membrane. DCIS is a heterogeneous group of pre-invasive breast cancers with various patterns of morphology, expansion, and malignant potential. The long-term prognosis of DCIS is excellent, with an expected overall 10-year survival rate that exceeds 95%, even in the absence of treatment [2]. 16% to 22% of women experience local relapse within 10 years following lumpectomy alone, and approximately one-half of these relapses are invasive breast cancer. Adjuvant radiotherapy reduces the 10-year risk of relapse to 7% to 9%, it is associated with cutaneous toxicity and a small long-term risk of secondary neoplasms [3,4,5]

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