title: Annexin A10 expression in colorectal cancers with emphasis on the serrated neoplasia pathway.
abstract: OBJECTIVE
  To validate the utility of Annexin A10 as a surrogate marker of the serrated neoplasia pathway in invasive colorectal cancers (CRCs).
  
  
  METHODS
  A total of 1133 primary CRC patients who underwent surgical resection at Seoul National University Hospital between January 2004 and December 2007 were enrolled. Expression of Annexin A10 was evaluated by immunohistochemistry using tissue microarray and paired to our findings on clinicopathologic and molecular characteristics of each individual. CpG island methylator phenotype was determined by MethyLight assay and microsatellite instability was determined by high performance liquid chromatography. KRAS and BRAF mutation status was evaluated by direct sequencing and allele-specific PCR. Univariate and stage-specific survival analyses were performed to reveal the prognostic value of Annexin A10 expression.
  
  
  RESULTS
  Annexin A10 expression was observed in 66 (5.8%) of the 1133 patients. Annexin A10 expression was more commonly found in females and was associated with proximal location, ulcerative gross type, advanced T category, N category and TNM stage. CRCs with Annexin A10 expression showed an absence of luminal necrosis, luminal serration and mucin production. CRCs with Annexin A10 expression were associated with CpG island methylator phenotype, microsatellite instability and BRAF mutation. In survival analysis, Annexin A10 expression was associated with poor overall survival and progression-free survival, especially in stage IV CRCs.
  
  
  CONCLUSIONS
  Annexin A10 expression is associated with poor clinical behavior and can be used a supportive surrogate marker of the serrated neoplasia pathway in invasive CRCs.
authors.affiliation: Jeong Mo Bae, Jung Ho Kim, Ye-Young Rhee, Nam-Yun Cho, Gyeong Hoon Kang, Laboratory of Epigenetics, Cancer Research Institute, Seoul National University College of Medicine, Seoul 110-799, South Korea.
authors.forename: Jeong Mo
authors.initials: JM
authors.lastname: Bae
authors.affiliation: Jeong Mo Bae, Jung Ho Kim, Ye-Young Rhee, Nam-Yun Cho, Gyeong Hoon Kang, Laboratory of Epigenetics, Cancer Research Institute, Seoul National University College of Medicine, Seoul 110-799, South Korea.
authors.forename: Jung Ho
authors.initials: JH
authors.lastname: Kim
authors.affiliation: Jeong Mo Bae, Jung Ho Kim, Ye-Young Rhee, Nam-Yun Cho, Gyeong Hoon Kang, Laboratory of Epigenetics, Cancer Research Institute, Seoul National University College of Medicine, Seoul 110-799, South Korea.
authors.forename: Ye-Young
authors.initials: YY
authors.lastname: Rhee
authors.affiliation: Jeong Mo Bae, Jung Ho Kim, Ye-Young Rhee, Nam-Yun Cho, Gyeong Hoon Kang, Laboratory of Epigenetics, Cancer Research Institute, Seoul National University College of Medicine, Seoul 110-799, South Korea.
authors.forename: Nam-Yun
authors.initials: NY
authors.lastname: Cho
authors.affiliation: Jeong Mo Bae, Jung Ho Kim, Ye-Young Rhee, Nam-Yun Cho, Gyeong Hoon Kang, Laboratory of Epigenetics, Cancer Research Institute, Seoul National University College of Medicine, Seoul 110-799, South Korea.
authors.forename: Tae-You
authors.initials: TY
authors.lastname: Kim
authors.affiliation: Jeong Mo Bae, Jung Ho Kim, Ye-Young Rhee, Nam-Yun Cho, Gyeong Hoon Kang, Laboratory of Epigenetics, Cancer Research Institute, Seoul National University College of Medicine, Seoul 110-799, South Korea.
authors.forename: Gyeong Hoon
authors.initials: GH
authors.lastname: Kang
mesh_terms: D000368:Aged; D017302:Annexins / Q000032:analysis*; D014408:Biomarkers, Tumor / Q000032:analysis* / Q000235:genetics; D015179:Colorectal Neoplasms / Q000737:chemistry* / Q000235:genetics / Q000401:mortality / Q000473:pathology / Q000628:therapy; D018899:CpG Islands; D019175:DNA Methylation; D004252:DNA Mutational Analysis; D018572:Disease-Free Survival; D005260:Female; D006785:Hospitals, University; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008297:Male; D053842:Microsatellite Instability; D008875:Middle Aged; D009154:Mutation; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D011237:Predictive Value of Tests; D016016:Proportional Hazards Models; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics; D015203:Reproducibility of Results; D056910:Republic of Korea; D012189:Retrospective Studies; D012307:Risk Factors; D046888:Tissue Array Analysis; D016896:Treatment Outcome
chemical_list: C121387:ANXA10 protein, human; D017302:Annexins; D014408:Biomarkers, Tumor; C117307:KRAS protein, human; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; D016283:Proto-Oncogene Proteins p21(ras)
keywords: Annexin A10; BRAF mutation; Colorectal cancer; CpG island methylator phenotype; Serrated neoplasia pathway