Loss of APAF-1 expression is associated with tumour progression and adverse prognosis in colorectal cancer

Abstract

The aim of this study was to determine the prognostic value of APAF-1 in colorectal cancer (CRC). Immunohistochemistry for APAF-1 was performed on a tissue microarray of 1015 mismatch-repair (MMR) proficient and 130 sporadic MLH1-negative CRCs. The association of APAF-1 with clinico-pathological features including 10-year survival time was analysed. Methylation specific PCR was performed on a subset of MMR-proficient and MLH1-negative CRC. Loss of APAF-1 was associated with advanced T stage ( p-value = 0.022), N stage ( p-value = 0.009), vascular invasion ( p-value = 0.001) and worse survival ( p-value = 0.017) in MMR-proficient CRC. In MLH1-negative CRC, loss of APAF-1 was associated with metastasis ( p-value = 0.041), worse prognosis ( p-value < 0.001) and independently predicted shorter survival time ( p-value < 0.001). No methylation was found in the selected region of APAF-1. APAF-1 is a marker of tumour progression in MMR-proficient CRC and an independent adverse prognostic factor in MLH1-negative CRC.