Molecular Subtypes of Ductal Carcinoma In Situ (DCIS) Identified by Expression of ER, PR, HER2, and Ki-67

Abstract

Objective: The estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), and Ki-67 are used to classify invasive breast cancer into various subtypes. In the case of ductal carcinoma in situ (DCIS), however, the information relating to subtypes using these markers is still limited. Methods: The pathological specimens of 267 patients diagnosed with DCIS at Siriraj Hospital were analyzed. By using the expressions of ER, PR, HER2, and Ki-67, breast cancer patients were classified into the five molecular subtypes: luminal A, luminal B/HER2 negative, luminal B/HER2 positive, HER2 overexpression, and triple-negative. Based on the specific molecular subtypes, age, clinical presentation, tumor size, and tumor grade were analyzed separately using univariate analysis. Results: 135 (50.6%), 1 (0.4%), 58 (21.7%), 59 (22.1%), and 14 (5.2%) DCIS were luminal A, luminal B/HER2 negative, luminal B/HER2 positive, HER2 overexpression, and triple-negative, respectively. Patients with luminal A DCIS significantly presented with mass, compared to the other subtypes that displayed with mass and microcalcification in combination (p = 0.008). The luminal A subtype was also associated with tumors of a smaller size (less than 2 cm; p = 0.007) and a lower nuclear grade (p = 0.000) than the HER2 overexpression subtype. Conclusion: Although luminal A DCIS was the most common DCIS subtype of Thai women, HER2 overexpression DCIS was significantly correlated with poor clinicopathological features, including a large tumor size and a high nuclear grade, which are recognized prognostic factors for tumor recurrence.