High EZH2 expression in ductal carcinoma in situ diagnosed on breast core needle biopsy is an independent predictive factor for upgrade on surgical excision

Approximately 25 % of DCIS diagnosed on breast core needle biopsy (CNB) is upgraded to invasive carcinoma on surgical excision. Risk factors to predict the upgrade on excision are not well established, leading many patients to be over or under-treated. EZH2 was shown to be associated with aggressive behavior of cancer from many sites, including breast cancer. We aimed to analyze EZH2 expression and tumor infiltrating lymphocytes (TILs) in DCIS as predictive factors for an upgrade on excision.

We assessed EZH2 expression in 34 DCIS cases diagnosed on CNB and upgraded to invasive carcinoma on excision. Then, we compared these cases with 60 control cases that were not upgraded on excision. A staining score for DCIS (0-12) was obtained by multiplying the staining intensity (0-3) and the percentage of positive cells (1-4). The nuclear staining score ≥6 was considered as 'high' expression.

46 of 94 (49 %) DCIS on CNB showed high EZH2 expression. EZH2 expression was directly correlated with TILs density, nuclear grade, HER2 expression, Ki-67 index and negative ER status. On univariate analysis, upgrade on excision was associated with high EZH2 expression, high TILs density, negative ER status and high Ki-67 index. Multivariate analysis revealed the high EZH2 expression as the only independent predictive factor for upgrade on excision.

Our study revealed the high EZH2 expression as the only independent predictive factor for an upgrade on excision. Future studies should focus on the evaluation of EZH2 expression in tumor-microenvironment interaction in terms of diagnostic, treatment and prognostic purposes.