title: 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.
authors.affiliation: Department of Pathology, McGill University, Duff Medical Building, 3775 University Street, Montreal, Canada H3A 2B4. inti.zlobec@elf.mcgill.ca
authors.forename: Inti
authors.initials: I
authors.lastname: Zlobec
authors.forename: Parham
authors.initials: P
authors.lastname: Minoo
authors.forename: Kristi
authors.initials: K
authors.lastname: Baker
authors.forename: David
authors.initials: D
authors.lastname: Haegert
authors.forename: Karim
authors.initials: K
authors.lastname: Khetani
authors.forename: Luigi
authors.initials: L
authors.lastname: Tornillo
authors.forename: Luigi
authors.initials: L
authors.lastname: Terracciano
authors.forename: Jeremy R
authors.initials: JR
authors.lastname: Jass
authors.forename: Alessandro
authors.initials: A
authors.lastname: Lugli
mesh_terms: D053477:Apoptotic Protease-Activating Factor 1 / Q000235:genetics / Q000378:metabolism*; D015179:Colorectal Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000401:mortality; D019175:DNA Methylation; D053843:DNA Mismatch Repair; D018450:Disease Progression; D006801:Humans; D007150:Immunohistochemistry; D015588:Observer Variation; D011379:Prognosis; D016019:Survival Analysis
chemical_list: C506592:APAF1 protein, human; D053477:Apoptotic Protease-Activating Factor 1