Breast Cancer and p16: Role in Proliferation, Malignant Transformation and Progression

Abstract

The definition of new molecular biomarkers could provide a more reliable approach in predicting the prognosis of invasive breast cancers (IBC). The aim of this study is to analyze the expression of p16 protein in IBC, as well as its participation in malignant transformation. The study included 147 patients diagnosed with IBC. The presence of non-invasive lesions (NIL) was noted in each IBC and surrounding tissue. p16 expression was determined by reading the percentage of nuclear and/or cytoplasmic expression in epithelial cells of IBC and NIL, but also in stromal fibroblasts. Results showed that expression of p16 increases with the progression of cytological changes in the epithelium; it is significantly higher in IBC compared to NIL (p < 0.0005). Cytoplasmic p16 expression is more prevalent in IBC (76.6%), as opposed to nuclear staining, which is characteristic of most NIL (21.1%). There is a difference in p16 expression between different molecular subtypes of IBC (p = 0.025). In the group of p16 positive tumors, pronounced mononuclear infiltrates (p = 0.047) and increased expression of p16 in stromal fibroblasts (p = 0.044) were noted. In conclusion, p16 protein plays an important role in proliferation, malignant transformation, as well as in progression from NIL to IBC.

Senescence in head and neck squamous cell carcinoma: relationship between senescence-associated secretory phenotype (SASP) mRNA expression level and clinicopathological features

“…In a study done by Jovanovic et al on breast cancer increased expression of p16 indicated malignant transformation of non-invasive lesions and suggested that p16 can be used as an additional diagnostic test in separating benign from malignant changes [ 17 ]. In another study by Zhou et al on colorectal cancer (CRC), p16 overexpression was correlated with Dukes stage, lymph node metastasis, and TNM stage (only in Caucasians) suggesting its effect on the development of CRC [ 18 ].…”

Unravelling the Intricate Roles of FAM111A and FAM111B: From Protease-Mediated Cellular Processes to Disease Implications

“…Notably, there was a marked decrease in the number of cells progressing through the S and G2/M phases of the cell cycle, and a higher proportion of cells remained in the G0/G1 phases. FAM111B was also shown to influence the degradation of p16 (CDKN2A), a protein responsible for delaying the G1/S transition by inhibiting the formation of the CDK 4/6—Cyclin D complex [ 24 , 26 ]. This complex is responsible for phosphorylating the retinoblastoma protein (pRb1), allowing for its dissociation from E2F and promoting cell cycle progression.…”

“…This complex is responsible for phosphorylating the retinoblastoma protein (pRb1), allowing for its dissociation from E2F and promoting cell cycle progression. If the DNA repair process is effective, FAM111B could initiate the resumption of the cell cycle by decreasing the levels of p16 ( Figure 3 a) [ 16 , 26 ].…”

Expression of p16 Tumor Suppressor Protein in Malignant Ovarian Germ Cell Tumors; Immunohistochemical Study

“…9,17 However, it is also expressed in some HPV-independent tumors as high-grade serous carcinomas of the ovary, 18 colorectal carcinomas, 19 and breast cancer. 20 Inactivation of p16 protein occurs in many tumors by different genetic and epigenetic mechanisms. [21][22][23] Loss of p16 expression was reported to be associated with poor prognosis in nasopharyngeal carcinomas 22 and in melanomas.…”