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In this retrospective study, we evaluated the prognostic significance and clinicopathological associations of p53 and HER2 expression in 290 surgically resected CRCs. Tissue microarrays from archival formalin-fixed paraffin-embedded samples were analyzed by immunohistochemistry. p53 expression was categorized into wild-type, overexpression, and null patterns, while HER2 was scored according to College of American Pathologists criteria used for gastric carcinoma. Survival analyses were performed using Kaplan\u2013Meier estimates, univariable and multivariable Cox regression, and restricted mean survival time, and immunohistochemical results were correlated with established clinicopathological and molecular features. Neither aberrant p53 expression nor HER2 positivity had a significant impact on 10-year overall survival. The p53 null phenotype showed a significantly increased relative risk of death within 5 years and a significant adverse effect in multivariable Cox regression of 5-year survival adjusted for age. Aberrant p53 expression was significantly associated with left-sided tumor location, mismatch repair proficiency, CK20 positivity, and MUC6 negativity, consistent with the chromosomal instability pathway of CRC. HER2 expression was infrequent and showed no prognostic relevance; however, HER2-positive tumors were significantly associated with CK7 expression, supporting an \u201cextraintestinal\u201d immunophenotypic profile reminiscent of right-sided or non-intestinal differentiation. In conclusion, while p53 and HER2 expression lacked independent prognostic value, their distinct associations with tumor phenotype underscore biologically relevant CRC subgroups.<\/jats:p>","DOI":"10.3389\/pore.2026.1612343","type":"journal-article","created":{"date-parts":[[2026,5,14]],"date-time":"2026-05-14T05:10:12Z","timestamp":1778735412000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Prognostic impact of p53 and HER2 immunohistochemistry profiles in colorectal carcinoma"],"prefix":"10.3389","volume":"32","author":[{"given":"Michal","family":"Grus","sequence":"first","affiliation":[{"name":"Department of Pathology, 3rd Faculty of Medicine, Charles University, University Hospital Kralovske Vinohrady","place":["Prague, Czechia"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hana","family":"Fi\u0161erov\u00e1","sequence":"additional","affiliation":[{"name":"Department of Pathology, 3rd 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