Affiliation:
1. Zhejiang University School of Medicine
2. Sir Run Run Shaw Hospital
Abstract
Abstract
Purpose
Ductal carcinoma in situ (DCIS) is regarded as non-invasive precursor lesion of invasive ductal carcinoma (IDC) but the molecular mechanisms and tumorigenesis behind DCIS progression remain to be elucidated. IDC sometimes present with a synchronous in-situ component (IDC-DCIS). The current study investigated the clinicopathological features that could predict DCIS progression and trace the origin of IDC.
Methods
Total 501 breast ductal carcinoma patients who underwent surgery as a first-line treatment between 2019 to 2022 from Sir Run Run Shaw Hospital were retrospectively reviewed. The clinical outcomes in different molecular subtypes and nuclear grade were evaluated.
Results
DCIS was significantly associated with a positive CK5/6 expression (P < 0.001), which was observed especially in HER2 overexpression subtype (P = 0.0027). Compared to IDC-DCIS, EGFR expression was significantly higher in IDC (P < 0.001) in triple-negative subtype (P < 0.001). In IDC-DCIS, co-expression of several biomarkers was observed in the DCIS component and IDC component. High grade DCIS component was significantly associated with HER2 and high Ki-67 (P < 0.001). Compared to pure DCIS, the in-situ component of IDC-DCIS was associated with high Ki-67 (P = 0.004), negative EGFR (P = 0.003), positive CK5/6 (P < 0.001) and high grade (P = 0.004).
Conclusion
Molecular subtypes, nuclear grade, and expressions of EGFR and CK5/6 resulted in different clinicopathological profiles in DCIS, IDC-DCIS and IDC. Presence of in-situ component is a marker of reduced aggressiveness and also supported that DCIS is the precursor lesion. Overall, our study traced the origin of IDC and propounded that HER2 targeted therapies could be of potential use in DCIS clinical trials.
Publisher
Research Square Platform LLC