Molecular Characterization of TP53 Variants in Exons 4-8 and p53 Immunoexpression in a Mexican Colorectal Cancer Cohort

Background/Objectives: Colorectal cancer (CRC) represents a major public health problem in Mexico and is among the malignancies with the highest morbidity and mortality. Alterations in TP53 are frequent molecular events in tumors with chromosomal instability; however, information on TP53 variants in the Mexican population, particularly in exons 4-8, remains limited. Exons 4-8 comprise the main coding region of the p53 DNA-binding domain; therefore, this study aimed to identify TP53 variants in these regions and evaluate p53 protein expression by immunohistochemistry in sporadic CRC. Methods: Tumor samples from 142 patients who underwent surgical resection without neoadjuvant treatment were analyzed. DNA was extracted from tumor tissue. TP53 exons 4-8 were amplified by polymerase chain reaction (PCR), and variants were identified by Sanger sequencing. p53 immunohistochemistry was performed in 40 tumors and 36 adjacent tissues, and nuclear expression was assessed using the Immunoreactivity Score. Results: Forty-three heterozygous variants were identified in 106/142 patients, representing 75% of the cohort. Thirty-one patients carried oncogenic variants, mainly clustered within the DNA-binding domain and involving hotspot residues such as Arg175, Tyr220, Gly245, Arg248, Arg273, and Arg282. Nuclear p53 expression was observed in 9/40 tumors, whereas all adjacent tissues were negative. Conclusions: TP53 alterations in exons 4-8 are frequent and heterogeneous in this Mexican cohort. Integrating mutational profiling with p53 immunohistochemistry provides complementary information for the biological interpretation of these tumors, including variants of translational interest.