Ghiarone, T.; Hansen, E.; Holaska, J. M.

Nuclear dysmorphism is a critical indicator of tumor aggressiveness, influencing cancer cell invasion and metastasis. Emerin, an integral nuclear envelope protein involved in nuclear architecture, is important for maintaining nuclear integrity. Our previous work demonstrated an inverse correlation between nuclear envelope-localized emerin expression and breast cancer aggressiveness. However, it failed to have the power to assess whether emerin loss correlates with cancer stage, grade, proliferation, or molecular phenotype. Here we analyzed emerin expression at the nuclear envelope across 243 breast cancer patient samples encompassing various tumor grades, stages, and molecular phenotypes. We found significantly reduced emerin expression in invasive ductal carcinoma (IDC), invasive lobular carcinoma (ILC), and ductal carcinoma in situ (DCIS), compared to normal breast tissue. Notably, emerin loss correlated with advanced tumor stage, higher Ki-67 proliferation rates, elevated human epidermal growth factor receptor 2 (HER2) levels, and decreased estrogen receptor (ER) and progesterone receptor (PR) expression - markers associated with more aggressive breast cancers. Emerin expression was consistently reduced in triple-negative breast cancer (TNBC) and other receptor-negative subtypes, underscoring its potential role in tumor dedifferentiation and progression. These findings highlight emerin as a promising prognostic biomarker and therapeutic target for aggressive breast cancer subtypes.