Spectrum of Ductal Carcinoma In Situ (DCIS) Lesions of the Breast: From Morphology to Molecular Characteristics.

Background Specific molecular characteristics of invasive breast cancer have been linked to an increased risk of early relapse. Similarly, ductal carcinoma in situ (DCIS) displays a comparable molecular profile, although their prevalence and implications are not yet fully understood. Aims and objectives The study design defined a multivariable statistical approach aimed at describing the interplay between the histopathological features of ductal carcinoma in situ (DCIS) and their molecular profile. The objective was to explore the correlations between the histopathological features of DCIS (tumor location, DCIS grade, DCIS type, and presence or absence of comedo necrosis) and various biomarkers like estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor (HER2/neu), androgen receptor (AR), and epidermal growth factor receptor (EGFR), in addition to the Ki-67 labeling index. Methods In this retrospective study, we selected and analyzed 100 diagnosed cases of ductal carcinoma in situ (DCIS) to represent various subtypes, grades, and morphological characteristics. A detailed histopathological review and immunohistopathological staining for ER, PR, HER2/neu, AR, EGFR, and Ki-67 were performed on formalin-fixed paraffin-embedded (FFPE) tumor tissue blocks. Molecular subtyping was done based on the biomarker analysis into luminal A, luminal B, luminal HER2/neu, HER2/neu enriched, and triple-negative subtypes. Statistical analysis was done to examine the correlation between tumor location, histopathological features of ductal carcinoma in situ (DCIS), and the expression of the immunohistochemical markers and the molecular subtypes. Results The majority of cases exhibited positivity for estrogen receptor (ER) and progesterone receptor (PR). A strong association was observed between histopathological features (DCIS grade, type, and comedo necrosis) of DCIS and ER/PR status. Additionally, a significant correlation was found between ductal carcinoma in situ (DCIS) grade and HER2/neu status. However, no association was identified between histopathological features and AR or EGFR status. Contrary to expectations, triple-negative DCIS did not show the most aggressive behavior, whereas HER2/neu-positive tumors, particularly high-grade ones, exhibited more aggressive features. No low-grade cases of luminal HER2/neu and HER2/neu-enriched tumors were found. A higher Ki-67 labeling index was found in cases with grade 3 and solid and comedo architectural types of DCIS, while low-grade tumors had a lower Ki-67 labeling index. Conclusion These findings suggest that hormone pathways play a crucial role in ductal carcinoma in situ (DCIS) progression, but the molecular interactions are complex and extend beyond simple binary associations. The complex relationship between the histopathological features of ductal carcinoma in situ (DCIS) and its hormone receptor status warrants further investigation with a larger sample size to fully understand the underlying mechanisms. The results challenge the expectation that triple-negative DCIS is the most aggressive subtype, highlighting the need for further research into the prognostic significance of different DCIS subtypes.