The metastatic potential of grade 1 Breast Carcinoma of No Special Type: a deep insight into putative molecular mechanisms.

The grade of a breast cancer (BC) is representative of the aggressive potential of the cancer. Usually, Grade 1 (G1) tumors do have the best prognosis in terms of recurrence and survival. Rarely can be found grade 1 tumors that metastasize to the axilla, suggesting a more aggressive behavior. The aim of this project is to uncover the mechanism responsible for the dissemination of tumor cells of G1 BC-NST into axillary lymph nodes in order to better understand lymph nodal metastasis phenomenon in breast cancer and stratify the patients for therapy. At present the scientific literature does not report anything about the molecular profile of grade 1 BC-NST with axillary metastasis so we decided to investigate this situation. We performed Whole Exome Sequencing (WES) on FFPE BC-NST G1 tumors. We analyzed 7 G1 Luminal A samples with metastasis and 8 without metastasis. From NGS results, we didn’t find any differences in the number of total mutations between the two groups. Analyzing the mutations with a major frequency, we found that two metastatic samples show single nucleotide polymorphisms (SNP) in AKT1, PI3KCA and KRAS genes that are correlated with cancer progression. Moreover, we identified the presence of one SNP in GPX6 gene (rs406113) (A>C) which is present only in metastatic group. In conclusion, from the results obtained we can state that the presence of the SNP rs406113 is associated with a more aggressive cellular behavior especially with regard to the migration capacities.