title: Genetic, immunohistochemical, and clinical features of medullary carcinoma of the pancreas: A newly described and characterized entity.
abstract: Medullary carcinomas of the pancreas are a recently described, histologically distinct subset of poorly differentiated adenocarcinomas that may have a unique pathogenesis and clinical course. To further evaluate these neoplasms, we studied genetic, pathological, and clinical features of 13 newly identified medullary carcinomas of the pancreas. Nine (69%) of these had wild-type K-ras genes, and one had microsatellite instability (MSI). This MSI medullary carcinoma, along with three previously reported MSI medullary carcinomas, were examined immunohistochemically for Mlh1 and Msh2 expression, and all four expressed Msh2 but did not express Mlh1. In contrast, all of the medullary carcinomas without MSI expressed both Msh2 and Mlh1. Remarkably, the MSI medullary carcinoma of the pancreas in the present series arose in a patient with a synchronous but histologically distinct cecal carcinoma that also had MSI and did not express Mlh1. The synchronous occurrence of two MSI carcinomas suggests an inherited basis for the development of these carcinomas. Indeed, the medullary phenotype, irrespective of MSI, was highly associated with a family history of cancer in first-degree relatives (P < 0.001). Finally, one medullary carcinoma with lymphoepithelioma-like features contained Epstein-Barr virus-encoded RNA-1 by in situ hybridization. Therefore, because of medullary carcinoma's special genetic, immunohistochemical, and clinical features, recognition of the medullary variant of pancreatic adenocarcinoma is important. Only by classifying medullary carcinoma as special subset of adenocarcinoma can we hope to further elucidate its unique pathogenesis.
authors.affiliation: Department of Pathology, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21231, USA.
authors.forename: R E
authors.initials: RE
authors.lastname: Wilentz
authors.forename: M
authors.initials: M
authors.lastname: Goggins
authors.forename: M
authors.initials: M
authors.lastname: Redston
authors.forename: V A
authors.initials: VA
authors.lastname: Marcus
authors.forename: N V
authors.initials: NV
authors.lastname: Adsay
authors.forename: T A
authors.initials: TA
authors.lastname: Sohn
authors.forename: S S
authors.initials: SS
authors.lastname: Kadkol
authors.forename: C J
authors.initials: CJ
authors.lastname: Yeo
authors.forename: M
authors.initials: M
authors.lastname: Choti
authors.forename: M
authors.initials: M
authors.lastname: Zahurak
authors.forename: K
authors.initials: K
authors.lastname: Johnson
authors.forename: M
authors.initials: M
authors.lastname: Tascilar
authors.forename: G J
authors.initials: GJ
authors.lastname: Offerhaus
authors.forename: R H
authors.initials: RH
authors.lastname: Hruban
authors.forename: S E
authors.initials: SE
authors.lastname: Kern
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018276:Carcinoma, Medullary / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D002352:Carrier Proteins; D004268:DNA-Binding Proteins; D020031:Epstein-Barr Virus Infections / Q000821:virology; D005192:Family Health; D005260:Female; D011905:Genes, ras / Q000235:genetics; D004854:Herpesvirus 4, Human / Q000235:genetics; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008297:Male; D018895:Microsatellite Repeats / Q000235:genetics; D008875:Middle Aged; D015999:Multivariate Analysis; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein; D009154:Mutation; D009363:Neoplasm Proteins / Q000032:analysis; D009687:Nuclear Proteins; D010179:Pancreas / Q000737:chemistry / Q000473:pathology / Q000821:virology; D010190:Pancreatic Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D010641:Phenotype; D011518:Proto-Oncogene Proteins / Q000032:analysis; D012367:RNA, Viral / Q000235:genetics; D016019:Survival Analysis
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D004268:DNA-Binding Proteins; C501486:MLH1 protein, human; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; D012367:RNA, Viral; C497172:MSH2 protein, human; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein