Analysis of TP53 gene and particular infrastructural alterations in invasive ductal mammary carcinoma

Abstract

This study was conducted in order to determine the mutational status of TP53 gene and to determine some particular aspects from ultrastructural level in invasive mammary ductal carcinoma. The cellular signaling pathway involving the TP53 gene acts in biological deoxyribonucleic acid (DNA) repair processes and cell cycle arrest following a signal transmitted to the p53 protein when posttranslational changes occur in the cell due to stress induced in the cell by both intrinsic and extrinsic factors. Cellular stress activates the transcription factor function of the protein that initiates, as the case may be, either DNA repair or programmed cell death (apoptosis). The TP53 gene is commonly mutated in many human cancers and also has a highly polymorphic grade. To determine the mutational status of the exons 4–9 of the TP53 gene, we used extracted DNA from fresh breast tissue, and we analyzed it through direct sequencing. In mammary carcinoma, the mutation frequency of TP53 is running between 20–40% and, in regards the polymorphism, at least 14 different forms were identified, that are associated with cancer risk. The mutation type distribution showed a predominance of deletions and a reduced frequency of substitutions comparing with International Agency for Research on Cancer (IARC) database. Taken in consideration the importance of the tumor associated stroma in tumor development, we have also investigated some particular aspects at the infrastructural level of invasive mammary ductal carcinoma, notably concerning telocytes as tumor stroma interstitial cells by transmission electron microscopy analysis.

Assessment of programmed death-ligand 1 receptor immunohistochemical expression and its association with tumor-infiltrating lymphocytes and p53 status in triple-negative breast cancer

“…Consistent with data from literature, we also demonstrated that an aberrant p53 immunoexpression has a prognostic value since its presence is associated with a worse DMFS. The mutant p53 protein acquired more functions than the “wild-type” p53 protein (normal immunoexpression) and can trigger the immune system by expressing itself on the tumor cell surface through histocompatibility complex (neoantigen) [ 22 , 43 , 44 ]. It was also demonstrated that mutation of TP 53 gene can lead to a poor reaction of CD8+ T-cells, which can affect the response to the immunotherapy [ 45 ].…”

Telocytes inside of the peripheral nervous system – a 3D endoneurial network and putative role in cell communication

“…Moreover, in different pathologies, TCs can be altered in their morphology and their number in surrounding stroma [19,[22][23][24]50]. In this line, Sabatelli et al (2022) [51] reported that in Ullrich congenital muscular dystrophya devastating inherited neuromuscular disorder [52] -, cluster of differentiation 34 (CD34)-positive TCs increase in their number in the interstitium of the deep fascia, Tps pass through dissoluted basal lamina and contact the sarcolemma of underlying muscle fiber aspects, which suggest a potential involvement of TCs in the pathogenesis.…”

“…During regeneration of post-injured skeletal muscle, TCs may activate and regulate satellite muscle cells activity by invading satellite cell niche by their long Tps through local destructured basal lamina succeeded to contact the adjacent activated satellite cells [ 49 ]. Moreover, in different pathologies, TCs can be altered in their morphology and their number in surrounding stroma [ 19 , 22 , 23 , 24 , 50 ]. In this line, Sabatelli et al (2022) [ 51 ] reported that in Ullrich congenital muscular dystrophy – a devastating inherited neuromuscular disorder [ 52 ] –, cluster of differentiation 34 (CD34)-positive TCs increase in their number in the interstitium of the deep fascia, Tps pass through dissoluted basal lamina and contact the sarcolemma of underlying muscle fiber aspects, which suggest a potential involvement of TCs in the pathogenesis.…”

“…TCs were described as a new stromal cell phenotype in almost normal tissue types [1,[6][7][8][9][10][11][12][13][14][15][16][17][18] or in a variety of disorders, including basal cell carcinoma (BCC) [19], fibrotic remodeling [20], uterine leiomyoma [21], mammary carcinoma [22][23][24][25], heart failure [26], atrial amyloidosis [27], etc.…”

“…Stromal cells are generally defined as heterogeneous population of resident or transiently cells mostly of mesenchymal origin represented by fibroblasts/fibrocytes, pericytes, telocytes (TCs), mostly located in perivascular niches [ 1 , 2 , 3 , 4 , 5 ]. TCs were described as a new stromal cell phenotype in almost normal tissue types [ 1 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 ] or in a variety of disorders, including basal cell carcinoma (BCC) [ 19 ], fibrotic remodeling [ 20 ], uterine leiomyoma [ 21 ], mammary carcinoma [ 22 , 23 , 24 , 25 ], heart failure [ 26 ], atrial amyloidosis [ 27 ], etc.…”