title: Low incidence of KRAS, BRAF, and PIK3CA mutations in adenocarcinomas of the ampulla of Vater and their prognostic value.
abstract: Ampullary adenocarcinomas (A-ACs) are rare malignancies with considerable importance because of their high curable resection rate and improved survival rate among periampullary cancers. The RAS-RAF-MAPK pathway is involved in the development of A-ACs and is a potential therapeutic target. However, molecular profiles of A-ACs and their prognostic impact are poorly understood. Peptide nucleic acid-mediated polymerase chain reaction clamping and Mutyper were used to detect KRAS, BRAF, and PIK3CA mutations in 62 paraffinized samples of A-ACs. Of 62 A-ACs, 30.6% had KRAS mutations, but no BRAF mutations and low frequency (1.6%) of PIK3CA mutation were detected. KRAS mutation was correlated with poor tumor differentiation and was a predictor of shorter recurrence-free survival period in overall A-ACs, whereas the prognosis according to the histologic subtypes was not affected by KRAS mutation. Lymph node metastasis was an independent prognostic factor of poor overall survival. Intestinal- and pancreatobiliary-type A-ACs had similar prognosis. Intestinal- and pancreatobiliary-type A-ACs had different prognostic factors; tumor differentiation and lymph node metastasis strongly predicted overall survival and recurrence-free survival in pancreatobiliary-type tumors, respectively, whereas no independent prognostic factors were demonstrated for intestinal-type tumors. Low incidence of KRAS mutations and their strong prognostic value in A-ACs may suggest the potential of survival benefit depending on the epidermal growth factor receptor-targeted therapy. Much lower frequencies of BRAF and PIK3CA mutations may suggest that they do not play a major role in the tumorigenesis of A-ACs. Different therapeutic protocols should be considered for treating pancreatobiliary- and intestinal-type A-ACs.
authors.affiliation: Department of Pathology, Hallym University Sacred Heart Hospital, Hallym University College of Medicine, Anyang, Gyeonggi-do 431-070, Republic of Korea.
authors.forename: Mi Jung
authors.initials: MJ
authors.lastname: Kwon
authors.affiliation: Department of Pathology, Kangnam Sacred Heart Hospital, Hallym University College of Medicine, Yeongdeungpo-gu, Seoul 150-950, Republic of Korea.
authors.forename: Jeong Won
authors.initials: JW
authors.lastname: Kim
authors.affiliation: Department of Surgery, Chuncheon Sacred Heart Hospital, Hallym University College of Medicine, Chuncheon, Gangweon-do 200-704, Republic of Korea.
authors.forename: Jae Pil
authors.initials: JP
authors.lastname: Jung
authors.affiliation: Department of Surgery, Hallym University Sacred Heart Hospital, Hallym University College of Medicine, Anyang, Gyeonggi-do 431-070, Republic of Korea.
authors.forename: Ji Woong
authors.initials: JW
authors.lastname: Cho
authors.affiliation: Department of Pathology, Kangdong Sacred Heart Hospital, Hallym University College of Medicine, Seoul 134-701, Republic of Korea.
authors.forename: Eun Sook
authors.initials: ES
authors.lastname: Nam
authors.affiliation: Department of Pathology, Kangdong Sacred Heart Hospital, Hallym University College of Medicine, Seoul 134-701, Republic of Korea.
authors.forename: Seong Jin
authors.initials: SJ
authors.lastname: Cho
authors.affiliation: Department of Surgery, Kangdong Sacred Heart Hospital, Hallym University College of Medicine, Seoul 134-701, Republic of Korea.
authors.forename: Joo Seop
authors.initials: JS
authors.lastname: Kim
authors.affiliation: Department of Pathology, Hallym University Sacred Heart Hospital, Hallym University College of Medicine, Anyang, Gyeonggi-do 431-070, Republic of Korea.
authors.forename: Hye-Rim
authors.initials: HR
authors.lastname: Park
authors.affiliation: Department of Pathology, Hallym University Sacred Heart Hospital, Hallym University College of Medicine, Anyang, Gyeonggi-do 431-070, Republic of Korea.
authors.forename: Soo Kee
authors.initials: SK
authors.lastname: Min
authors.affiliation: Department of Pathology, Hallym University Sacred Heart Hospital, Hallym University College of Medicine, Anyang, Gyeonggi-do 431-070, Republic of Korea.
authors.forename: Jinwon
authors.initials: J
authors.lastname: Seo
authors.affiliation: Department of Pathology, Hallym University Sacred Heart Hospital, Hallym University College of Medicine, Anyang, Gyeonggi-do 431-070, Republic of Korea.
authors.forename: Kyueng-Whan
authors.initials: KW
authors.lastname: Min
authors.affiliation: Department of Pathology, Dongtan Sacred Heart Hospital, Hallym University College of Medicine, Hwaseong, Gyeonggi-do 445-170, Republic of Korea. Electronic address: homed@hallym.or.kr.
authors.forename: Dong Hoon
authors.initials: DH
authors.lastname: Kim
authors.affiliation: Department of Surgery, Hallym University Sacred Heart Hospital, Hallym University College of Medicine, Anyang, Gyeonggi-do 431-070, Republic of Korea. Electronic address: jjy1030@hallym.or.kr.
authors.forename: Jang Yong
authors.initials: JY
authors.lastname: Jeon
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics* / Q000401:mortality / Q000473:pathology / Q000628:therapy; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014670:Ampulla of Vater / Q000473:pathology; D014408:Biomarkers, Tumor / Q000235:genetics*; D002454:Cell Differentiation; D058534:Class I Phosphatidylinositol 3-Kinases; D003138:Common Bile Duct Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology / Q000628:therapy; D004252:DNA Mutational Analysis / Q000379:methods; D018572:Disease-Free Survival; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010641:Phenotype; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics*; D016133:Polymerase Chain Reaction; 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*; D056910:Republic of Korea; D012307:Risk Factors; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D014408:Biomarkers, Tumor; C117307:KRAS protein, human; D019869:Phosphatidylinositol 3-Kinases; D058534:Class I Phosphatidylinositol 3-Kinases; C484760:PIK3CA protein, human; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; D016283:Proto-Oncogene Proteins p21(ras)
keywords: Adenocarcinoma; Ampulla of Vater; BRAF; KRAS; Mutation; PIK3CA; Prognosis