Searching for Novel Molecular Prognostic Markers in Colorectal Cancer-The Tumor Suppressor Proteins p53 and PTEN

Background: Colorectal cancer (CRC) remains a leading cause of cancer-related morbidity and mortality worldwide. While established molecular biomarkers such as microsatellite instability (MSI), KRAS, and BRAF are routinely used in clinical practice, the prognostic relevance of tumor suppressor proteins p53 and PTEN remains incompletely defined, particularly when assessed using immunohistochemistry. Objective: The primary aim of this study was to evaluate the prognostic significance of p53 expression and PTEN deficiency in colorectal adenocarcinoma. Secondary aims included assessment of their association with clinicopathological characteristics. Methods: This retrospective cohort study included 103 consecutive patients who underwent surgical resection for colorectal adenocarcinoma. Immunohistochemical analysis of formalin-fixed paraffin-embedded (FFPE) tumor samples was performed to assess aberrant p53 expression and PTEN deficiency. Associations with clinicopathological variables were evaluated, and overall survival was analyzed using Kaplan-Meier curves and Cox proportional hazards regression models. Results: Aberrant p53 expression and PTEN deficiency were both associated with shorter overall survival in univariate analyses. Patients with concurrent aberrant p53 expression and PTEN deficiency demonstrated the poorest survival outcomes. However, in multivariate Cox regression analysis, only nodal status and age remained independent predictors of overall survival, while p53 and PTEN did not retain independent prognostic significance after adjustment for clinicopathological variables. Conclusions: Aberrant p53 expression and PTEN deficiency are associated with reduced overall survival in colorectal cancer; however, their prognostic impact appears secondary to established clinicopathological factors. The combined presence of these alterations may identify a biologically aggressive subgroup of patients with particularly unfavorable outcomes, although this observation should be considered exploratory. Further validation in larger, independent cohorts is required.