PTEN status, tumor immune microenvironment, and survival in colorectal cancer

Abstract

Phosphatase and tensin homolog (PTEN) is a tumor suppressor involved in cell proliferation, DNA repair, apoptosis, and cell cycle regulation. Its loss has been linked to worse prognosis and poor immune therapy response in several cancers, but findings in colorectal cancer (CRC) have been inconsistent. This study aims to evaluate the prognostic value of PTEN expression and its relationship with the tumor immune microenvironment in two large CRC cohorts (combined N = 2303). PTEN expression was assessed by immunohistochemistry and categorized as intact, reduced, or lost. Additionally, three multiplex immunohistochemistry assays were used to assess immune cell composition and expression of immunosuppressive markers within the tumor environment. PTEN loss was observed in 12% of tumors in cohort 1 and 11% in cohort 2. PTEN expression status showed no significant prognostic value. For CRC-specific mortality, the multivariable HR for PTEN loss (vs. intact expression) was 1.19 (95% CI 0.88–1.61) in cohort 1 and 0.85 (95% CI 0.55–1.31) in cohort 2. PTEN loss was associated with BRAF mutations and mismatch repair (MMR) deficiency in both cohorts, but was not independently associated with tumor immune cell composition or expression of PD-L1, PD-1, IDO, and ARG1. In conclusion, PTEN immunohistochemistry lacked prognostic value in CRC and did not reflect the tumor immune landscape. These findings suggest that PTEN immunohistochemistry alone may have limited clinical utility as a biomarker in CRC, highlighting the need for complementary genomic profiling in future studies.