Loss of APAF-1 expression is associated with tumour progression and adverse prognosis in colorectal cancer.
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.
Zlobec
Inti
I
Department of Pathology, McGill University, Duff Medical Building, 3775 University Street, Montreal, Canada H3A 2B4. inti.zlobec@elf.mcgill.ca
Minoo
Parham
P
Baker
Kristi
K
Haegert
David
D
Khetani
Karim
K
Tornillo
Luigi
L
Terracciano
Luigi
L
Jass
Jeremy R
JR
Lugli
Alessandro
A
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
C506592:APAF1 protein, human; D053477:Apoptotic Protease-Activating Factor 1