ESPRESSIONE DI SEL1L NEL CARCINOMA MAMMARIO - CORRELAZIONI CLINICO PATOLOGICHE

Malignant cells exhibit an exceptional ability to maintain homeostasis in an hostile environment, upregulation of proteins involved in the stress response with an increase in the apoptosis resistance, and in diminishing cell senescence or permanent arrest of cell division. SEL1L is a member of endoplasmic-reticulum (ER)-associated protein degradation (ERAD)-specific ubiquitin ligase complex that functions in the detection, targeting, and degradation of malfolded and normal endoplasmic reticulum (ER) resident proteins in fisiologic or pathologic conditions. Past studies have focused on the role of SEL1L in various aspects of malignant transformation and tumorigenic processes, providing significant in vitro and in vivo evidences to link its increased expression to a decrease in breast tumor aggressiveness. In this study it has been suggested that SEL1L protein could be also a tumor breast markers with a prognostic and/or predictive response and this may be important in determining the successive therapeutic approach. In patients of Black African ethnicity, breast cancer strongly differ from Western populations in ethnicity, lifestyle and environmental exposures and is reportedly to be characterized by aggressive, poorly differentiated phenotype(s). To highlight possible differences between breast cancer in indigenous sub-Saharan African and European patients, two breast cancer case series, from Central Sudan (Khartoum) and Northern Italy (Milan), were compared for clinicopathological characteristics, expression of oestrogen receptor (ER), progesterone receptor (PR), Her-2/neu, and breast cancer subtypes and for SEL1L expression. SEL1L protein expression was evaluated by immunohistochemistry using the mouse MAb MSel1 raised against the NH2 terminus of the recombinant human SEL1L protein. Compared with the Italian series, the Sudanese breast cancer series showed younger age and worse prognostic features, including larger tumour size, higher grade and LN+ status, consistent with more advanced stage at disease diagnosis. Results showed that no clear significant differences between the Sudanese and Italian series were found for SEL1L expression levels combined with clinicopathological characteristics, including nodal involvement, tumor size, grade, with hormone receptor status (ER and/or PR), Her-2/neu status and with breast cancer subtypes (Luminal A, Luminal B, Her-2/neu+ and basal-like). The clinicopathological differences between breast cancer in indigenous sub-Saharan African and European patients probably reflects the young demographic structure of the Sudanese population, the lack of breast cancer prevention, the extreme rarity of healthcare centres able to treat breast cancer and, possibly, the influence of socio-cultural and logistic factors which could limit travel and access to healthcare. In conclusion, SEL1L protein expression is not a tumor marker however the role of SEL1L during tumorigenesis and in breast cancer needs further investigation.