title: Adenosquamous carcinoma of the pancreas harbors KRAS2, DPC4 and TP53 molecular alterations similar to pancreatic ductal adenocarcinoma.
abstract: Adenosquamous carcinoma of the pancreas is one of the most aggressive forms of pancreatic cancer. Molecular characterizations of this rare tumor subtype are sparse. Understanding the common molecular and pathologic features of pancreatic adenosquamous carcinomas could provide critical information for identifying therapeutic targets. Herein, we analyzed the pathologic and molecular features of our series of eight pancreatic adenosquamous carcinomas. We found KRAS2 gene mutations at codon 12 in all eight cases. All the cases showed loss of p16 protein. In three of these cases the loss was attributed to an exon 2 homozygous deletion in the p16/CDKN2a gene. The majority of the cases had loss of Dpc4 protein and strong nuclear p53 positivity, similar to the molecular signature found in pancreatic ductal adenocarcinoma. We found that E-cadherin was either lost or reduced in all cases and that epidermal growth factor receptor was overexpressed in all cases. The squamous component was positive for p63 staining and thus p63 labeling was helpful in identifying squamous differentiation in adenosquamous carcinomas with an acantholytic growth pattern. In summary, although pancreatic adenosquamous carcinoma and ductal adenocarcinoma have overlapping pathologic and molecular characteristics, there are distinct differences that may be helpful in diagnostic and therapeutic strategies.
authors.affiliation: Department of Surgery, Thomas Jefferson University, Philadelphia, PA, USA.
authors.forename: Jonathan R
authors.initials: JR
authors.lastname: Brody
authors.forename: Christina L
authors.initials: CL
authors.lastname: Costantino
authors.forename: Magdalena
authors.initials: M
authors.lastname: Potoczek
authors.forename: Joseph
authors.initials: J
authors.lastname: Cozzitorto
authors.forename: Peter
authors.initials: P
authors.lastname: McCue
authors.forename: Charles J
authors.initials: CJ
authors.lastname: Yeo
authors.forename: Ralph H
authors.initials: RH
authors.lastname: Hruban
authors.forename: Agnieszka K
authors.initials: AK
authors.lastname: Witkiewicz
mesh_terms: D000368:Aged; D015820:Cadherins / Q000096:biosynthesis; D018196:Carcinoma, Adenosquamous / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D021441:Carcinoma, Pancreatic Ductal / Q000235:genetics*; D004252:DNA Mutational Analysis; D004268:DNA-Binding Proteins / Q000235:genetics*; D066246:ErbB Receptors / Q000096:biosynthesis; D005260:Female; D015870:Gene Expression; D019942:Genes, p16; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008565:Membrane Proteins / Q000096:biosynthesis; D008875:Middle Aged; D009154:Mutation; D010190:Pancreatic Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D016133:Polymerase Chain Reaction; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D016283:Proto-Oncogene Proteins p21(ras); D051901:Smad4 Protein / Q000235:genetics*; D018631:ras Proteins / Q000235:genetics*
chemical_list: C081876:CKAP4 protein, human; D015820:Cadherins; D004268:DNA-Binding Proteins; C117307:KRAS protein, human; D008565:Membrane Proteins; D011518:Proto-Oncogene Proteins; C497796:SMAD4 protein, human; D051901:Smad4 Protein; C114495:TP53TG1 protein, human; D066246:ErbB Receptors; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins