Determination of HER2 and p53 Mutations by Sequence Analysis Method and EGFR/Chromosome 7 Gene Status by Fluorescence in Situ Hybridization for the Predilection of Targeted Therapy Modalities in Immunohistochemically Triple Negative Breast Carcinomas in Turkish Population

Abstract

Triple negative breast cancer (TNBC), an agressive subtype accounts nearly 15 % of all breast carcinomas. Conventional chemotherapy is the only treatment modality thus new, effective targeted therapy methods have been investigated. Epidermal growth factor receptor (EGFR) inhibitors give hope according to the recent studies results. Also therapeutic agents have been tried against aberrant p53 signal activity as TNBC show high p53 mutation rates. Our aim was to detect the incidence of mutations/amplifications identified in TNBC in our population. Here we used sequence analysis to detect HER2 (exon 18-23), p53 (exon 5-8) mutations; fluorescence in situ hybridization (FISH) method to analyse EGFR/chromosome 7 centromere gene status in 82 immunohistochemically TNBC. Basaloid phenotype was identified in 49 (59.8 %) patients. EGFR amplification was noted in 5 cases (6.1 %). All EGFR amplified cases showed EGFR overexpression by immunohistochemistry (IHC). p53 mutations were identified in 33 (40.2 %) cases. Almost 60 % of the basal like breast cancer cases showed p53 mutation. Only one case showed HER2 mutation (exon 20:g.36830_3). Our results showed that gene amplification is not the unique mechanism in EGFR overexpression. IHC might be used in the decision of anti-EGFR therapy in routine practice. p53 mutation rate was lower than the rates reported in the literature probably due to ethnic differences and low sensitivity of sanger sequences in general mutation screening. We also established the rarity of HER2 mutation in TNBC. In conclusion EGFR and p53 are the major targets in TNBC also for our population.

Current biomarkers of canine mammary tumors

“…In human patients, a mutation of p53 is found in the majority of HBC, especially in more aggressive types, such as triple negative breast cancer [ 44 , 45 ]. High expression of p53 correlates positively with a worse prognosis and shorter survival time [ 45 ].…”

Prognostic Evaluation of Epidermal Growth Factor Receptor (EGFR) Genotype and Phenotype Parameters in Triple-negative Breast Cancers

“…However, only one out of eleven amplified tumors was a metaplastic carcinoma (one out of seventeen such tumors) in our series. EGFR gene amplification has been described to result in increased protein expression in breast carcinomas (66,67,72,73) implying that the multiple gene copies have downstream effects on EGFR mRNA and protein. Our results are concordant with these findings at both the mRNA and protein level for tumors informative with all methods, although the amplified group was too small to yield statistically significant results.…”

Exploring the contrasts: in-depth analysis of human and canine mammary tumors - discoveries at the frontier

“…PCNA, a DNA polymerase protein, signifies the proliferation index (PI), peaking in late G1 phase and remaining elevated through G2 and M phases [ 38 ]. In human medicine, PCNA serves as a primary proliferation biomarker, often evaluated alongside other HBC markers [ 35 ].…”

“…Similar to Ki-67, PCNA expression is higher in malignant tumors, indicating poor prognosis and lower survival rates [ 39 ]. Combining PCNA with other biomarkers, particularly Ki-67, enhances prognostic accuracy due to its cell cycle-specific expression [ 38 ].…”

“…Combining PCNA with other biomarkers, particularly Ki-67, enhances prognostic accuracy due to its cell cyclespecific expression [38].…”