CD10 expression and risk of relapse in DCIS

Abstract

e22053 Background: DCIS is a heterogeneous malignant condition of the breast with no standard of care. The Van Nuys Prognostic Index (VNPI) is the most useful tool to predict local recurrence. However, assessment of the VNPI score is not easy and many women with DCIS are offered the same treatment. Experimental evidence has indicated that a local death of the myo-epithelial cells (MECs) in the DCIS is a pre-requisite to tumor invasion. In this study we hypothesized that loss of CD10, (a marker of MECs), would be a surrogate for basement membrane disruption and tumor invasion. The aim of the present study was to retrospectively evaluate the prognostic value of CD10 in DCIS. Methods: CD10 expression was evaluated by qRT-PCR and immuno-histochemistry (IHC) using FFPE tissues on normal samples (N=11) and two independent DCIS populations: a training set (N=66) and a validating set (N=88). Results: MECs were the only cells that showed a CD10 staining using IHC in normal and DCIS samples. All normal tissue samples demonstrated high expression levels of CD10 using both IHC and RT-PCR. In contrast, DCIS samples showed a wide range of CD10 expression levels. Of interest, 66% of DCIS showed lower expression values of CD10 compared to normal tissues. The group of DCIS with low expression of CD10 was statistically associated with higher risk of relapse [HR: 2.49 (CI.95%= 1.13–5.49), P= 0.02]. These results were independently validated in our validation set using both techniques (qRT-PCR: HR: 1.805 (CI.95%= 1.11–2.92), P= 0.02]; IHC [HR: 1.84 (CI.95%= 1.00–3.40), P= 0.05]. In multivariate analysis, CD10 remained significant (HR=2.25; [95CI: 1.24–4.09], p=0.008) together with VNPI [HR: 2.03 (CI.95%= 1.23–3.35), P= 0.006]. Conclusions: Decrease of CD10 expression in MECs is associated with higher risk of relapse in DCIS and it has the potential to improve DCIS management. These promising results are currently being validated in a larger patient's series. No significant financial relationships to disclose.