Basal Cytokeratin in Ductal Carcinoma in Situ: Potential Marker of Low Risk of Invasive Disease

Abstract

INTRODUCTION: The prevalence of DCIS has been rising in the last decades, probably due to better screening programs. This increase in the diagnosed cases of DCIS shows the heterogeneity of the group, particularly the risk of associated invasive disease and the risk of recurrences, most of these as invasive cancer. We investigated the role of basal cytokeratin 5/6 (CK5/6) in the risk of invasion of ductal carcinoma in situ (DCIS). MATERIAL AND METHODS: Tissue microarrays from 236 DCIS samples, consisting of 90 without invasive ductal carcinoma (IDC) (group 1) and 146 with IDC (group 2), with both groups having similar patient age and nuclear grade, were compared in terms of estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), CK5/6, epidermal growth factor receptor, and the immunohistochemically defined molecular subtype. RESULTS: ER- and PR-negative status was associated with a invasion component (OR 4.67, CI 1.87- 11.70), whereas HER2-positive and CK5/6-positive status was negatively associated with invasion. Among high-grade tumors, the hybrid luminal/HER2 profile and CK5/6 were negatively associated with invasion. In low-grade DCIS, only CK5/6 showed a negative impact on the probability of invasion (OR 0.22, CI 0.09-0.57). DISCUSSION AND CONCLUSIONS: Our results suggest that the low-grade DCIS patients that would benefit more with conservative approaches would be those with CK5/6 expression, regardless of the molecular profile. On the other hand, high-grade DCIS with the triple-positive phenotype (ER/PR/ HER2) and CK5/6 expression might correspond to less aggressive lesions.