title: Pyloric gland adenoma in Lynch syndrome.
abstract: The prevalence of gastric cancer associated with Lynch syndrome (LS) is highly variable, and the underlying histologic pathway or molecular mechanisms remain unclear. From 1995 to 2012, 15 patients had been treated for both gastric and colonic adenocarcinomas and diagnosed as LS. In all cases, pathologic review, immunohistochemical analysis for mismatch-repair proteins, and microsatellite instability (MSI) tests were performed. To confirm LS, germline mutation tests and multiplex ligation-dependent probe amplification were performed. All gastric and colonic carcinomas were MSI-high and lost expressions of MLH1/PMS2 in 11 (73%) cases and MSH2/MSH6 in 4 (27%) cases. Remarkably, in a patient with LS and germline mutation of MLH1 gene, pyloric gland adenoma (PGA) transformed to adenocarcinoma during follow-up. In 2 additional cases, PGA was found adjacent to advanced gastric cancers. All PGAs in LS patients were MSI-high and lost expression of mismatch-repair proteins (MLH1/PMS2 in 2 cases and MSH2/MSH6 in 1 case), whereas none of the 14 sporadic PGAs was MSI-high or had lost expression of mismatch-repair proteins. On the basis of these observations, although very rare, we suggest the possibility that PGA may be a precursor lesion to gastric adenocarcinoma in LS and that the mismatch-repair deficient pathway of carcinogenesis is involved early in the gastric carcinogenesis pathway.
authors: Departments of *Pathology †Gastroenterology ‡Laboratory Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea §Clinical Laboratory Division, National Cancer Center Hospital, Tokyo, Japan ∥Department of Pathology, Massachusetts General Hospital, Boston, MA.
authors: Seung Eun
authors: SE
authors: Lee
authors: So Young
authors: SY
authors: Kang
authors: Junhun
authors: J
authors: Cho
authors: Boram
authors: B
authors: Lee
authors: Dong Kyung
authors: DK
authors: Chang
authors: Hyein
authors: H
authors: Woo
authors: Jong Won
authors: JW
authors: Kim
authors: Ha Young
authors: HY
authors: Park
authors: In Gu
authors: IG
authors: Do
authors: Young Eun
authors: YE
authors: Kim
authors: Ryoji
authors: R
authors: Kushima
authors: Gregory Y
authors: GY
authors: Lauwers
authors: Cheol Keun
authors: CK
authors: Park
authors: Kyoung M
authors: KM
authors: Kim
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000032:analysis; D000230:Adenocarcinoma / Q000737:chemistry / Q000235:genetics / Q000473:pathology*; D000236:Adenoma / Q000737:chemistry / Q000235:genetics / Q000473:pathology*; D000251:Adenosine Triphosphatases / Q000032:analysis; D000328:Adult; D014408:Biomarkers, Tumor / Q000032:analysis / Q000235:genetics; D003123:Colorectal Neoplasms, Hereditary Nonpolyposis / Q000737:chemistry / Q000235:genetics / Q000473:pathology*; D053843:DNA Mismatch Repair; D004252:DNA Mutational Analysis; D045643:DNA Repair Enzymes / Q000032:analysis; D004268:DNA-Binding Proteins / Q000032:analysis; D018450:Disease Progression; D005260:Female; D005752:Gastric Mucins / Q000032:analysis; D005753:Gastric Mucosa / Q000737:chemistry / Q000473:pathology*; D005773:Gastroscopy; D018095:Germ-Line Mutation; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D053842:Microsatellite Instability; D008875:Middle Aged; D000070976:Mismatch Repair Endonuclease PMS2; D000070957:MutL Protein Homolog 1; D009687:Nuclear Proteins / Q000032:analysis; D011379:Prognosis; D013274:Stomach Neoplasms / Q000737:chemistry / Q000235:genetics / Q000473:pathology*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; D005752:Gastric Mucins; C501486:MLH1 protein, human; D009687:Nuclear Proteins; D000251:Adenosine Triphosphatases; C094934:PMS2 protein, human; D000070976:Mismatch Repair Endonuclease PMS2; D000070957:MutL Protein Homolog 1; D045643:DNA Repair Enzymes