DCIS have neoplastic cells which proliferate within the ducts. The duct is bound by the basement membrane along with a rim of myoepithelial cells which are on the lumen of the basement membrane. Unlike normal breast ducts which are composed of a single epithelial layer, the lesions of DCIS has multiple layers of cells that increase into to lumen. Blood vessels, lymphatics, immune cells, and lymphatics either promotes or suppress malignant progenitor cells which may rise inside the mass of cells multiplying in the ducts plays a role in carcinogenesis. In the center of the ducts, necrosis occurs because the cells are the furthest from nutrients that circulate from the vessels outside the ducts. These proliferating cells are highly stressed due to being nutrient deprived, hypoxic, crowded and oxidative stress and mammary pluripotent stem cells are compelled to adapt to survive. This adaptation promotes apoptosis suppression which can result in a generation of genetically abnormal malignant progenitor cells before invasions (Espina 69).
Hereditary breast cancer—which is five percent of all breast cancer—is caused by a germ line mutation in BRCA1 BRCA2 genes. BRCA1 mutation related breast cancer is genetically different along with being morphologically and immunohistochemical’s phenotype being different from non-BCRA mutation related breast cancer. BRCA2 mutation-related breast cancer is genetically different from non-BRCA mutation related breast cancer, but it is difficult to differentiate BRCA2 breast cancer’s phenotype from non-BRCA breast cancer’s phenotype (Van der Groep et. al 1).
In non-BRCA mutation related breast cancer, hypoxia is present. Hypoxia is a “state of lower-than-normal oxygen tension” (Weinberg 265). Hypoxia response is regulated by hypoxia induced factor-1 (HIF-1). Under normal oxygen tension (normoxia), prolyl hydroxylases (PHD1-PHD3) uses oxygen as a substrate to adjust the proline residues on HIF-1α (oxygen dependent). Von Hippel-Lindu (VHL) tumor suppresser protein through the ubiquitin ligase complex recognizes HIF-1α and targets proteasomal degradation (Espina 70).
Ataxia telangiectasia mutated (ATM), tumor protein p53 (TP53), check point kinase 2 (CHEK2), and Phosphatase and tensin homolog (PTEN) are less frequent gene mutations in breast cancer than BRCA. When it’s not mutated, ATM helps repair damaged DNA. However, if one mutated ATM genes are inherited, is associated with high breast cancer rates in families. TP53 helps my make p53. P53 is a protein that inhibits tumor growth. If mutation of TP53 is passed down hereditarily, it can result in Li-Fraumeni syndrome. Though Li-Fraumeni syndrome is a rare cause of breast cancer, those with this syndrome can develop breast cancer. Mutation in CHEK2 can also result in Li-Fraumeni syndrome. Though PTN regulates cell growth normally, it causes Cowden syndrome when mutated. This disorder increases changes of developing both malignant and benign breast tumor...