title: Prognostic significance of mammalian sterile20-like kinase 1 in colorectal cancer.
abstract: Mammalian Sterile20-like kinase 1 (Mst1) is a member of the yeast Ste20-related kinase family known to be involved in the process of apoptosis initiated by a variety of stimuli. The aim of this study was to determine the prognostic significance of Mst1 expression in colorectal cancer. A series of 1197 mismatch-repair-proficient colorectal cancers retrieved from a tissue microarray were randomized into two study groups. On the first group (n=599) receiver operating characteristic curves were used to determine the most clinically useful cutoffs to describe Mst1 expression with respect to T stage, N stage, tumor grade, vascular invasion and overall survival. The association of Mst1 expression and each outcome was immunohistochemically evaluated on the second study group (n=598) as well as on a third study group comprising 141 mismatch-repair-deficient colorectal cancers. A univariate analysis in the second study group showed that loss of cytoplasmic Mst1 was associated with higher T stage (P=0.001), higher N stage (P=0.029), vascular invasion (P=0.017) and overall survival (P=0.014). Nuclear Mst1 expression was not significantly associated with N stage, T stage or vascular invasion but was associated with tumor grade. In mismatch-repair-deficient colorectal cancers, loss of cytoplasmic Mst1 was associated with higher N stage (P=0.019) and shortened survival (P=0.0001). In a multivariate analysis, loss of cytoplasmic Mst1 was an independent adverse prognostic factor in this group of patients. Methylation analysis on 32 cases showed that the loss of cytoplasmic Mst1 expression is not likely due to promoter methylation. In summary, loss of cytoplasmic Mst1 expression is a marker of tumor progression in mismatch-repair-proficient as well as mismatch-repair-deficient colorectal cancers. These results are suggestive of a tumor suppressor role for Mst1 in human colorectal cancer.
authors.affiliation: Department of Pathology, McGill University, Montreal, QC, Canada. parham.minoo@mcgill.ca
authors.forename: Parham
authors.initials: P
authors.lastname: Minoo
authors.forename: Inti
authors.initials: I
authors.lastname: Zlobec
authors.forename: Kristi
authors.initials: K
authors.lastname: Baker
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: D014408:Biomarkers, Tumor / Q000032:analysis*; D015179:Colorectal Neoplasms / Q000201:enzymology* / Q000401:mortality / Q000473:pathology*; D019175:DNA Methylation; D053843:DNA Mismatch Repair; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D047908:Intracellular Signaling Peptides and Proteins; D008297:Male; D009367:Neoplasm Staging; D016133:Polymerase Chain Reaction; D011379:Prognosis; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D012372:ROC Curve; D016019:Survival Analysis; D046888:Tissue Array Analysis; D000099317:Hippo Kinases
chemical_list: D014408:Biomarkers, Tumor; D047908:Intracellular Signaling Peptides and Proteins; D017346:Protein Serine-Threonine Kinases; C095566:STK4 protein, human; D000099317:Hippo Kinases