title: Immunohistochemical investigation of tumorigenic pathways in sinonasal intestinal-type adenocarcinoma. A tissue microarray analysis of 62 cases.
abstract: OBJECTIVE
  Sinonasal intestinal-type adenocarcinoma (ITAC) is an uncommon neoplasm morphologically similar to colorectal adenocarcinoma, with a well-recognized association with occupational exposure to wood or leather dusts. Here, we analyse several gene products with pivotal roles in tumorigenesis, including p53, p16, deleted in colon cancer (DCC), retinoblastoma, adenomatous polyposis coli, β-catenin, E-cadherin and CD10, and discuss their relation to clinical behaviour and to similar pathways in colorectal adenocarcinomas.
  
  
  RESULTS
  Immunohistochemical analysis of 62 ITACs was conducted on a tissue microarray. Aberrant expression of p53 and p16 were the most commonly observed alterations (61.3% and 64.5% of cases, respectively). Analysis according to the histological subtype showed that p53 overexpression was less frequent in mucinous ITACs (35.3% versus 71.1%, P = 0.018), while loss of DCC and E-cadherin were observed more frequently in this subtype (76.5% versus 31.1%, P=0.002 and 82.4% versus 31.1%, P<0.001, respectively). No correlation was found between the aberrant expression of these and clinical behaviour while mucinous adenocarcinomas had a significantly worse prognosis, with shorter disease-free interval and overall survival (P=0.005 and P<0.001, respectively).
  
  
  CONCLUSIONS
  Mucinous ITACs appear to follow a distinct molecular pathway(s) from the non-mucinous variants, and pursue an aggressive clinical behaviour.
authors.affiliation: Division of Anatomic Pathology, Department of Critical Care Medicine and Surgery, University of Florence Medical School, Florence, Italy. franchi@unifi.it
authors.forename: Alessandro
authors.initials: A
authors.lastname: Franchi
authors.forename: Annarita
authors.initials: A
authors.lastname: Palomba
authors.forename: Cristina
authors.initials: C
authors.lastname: Fondi
authors.forename: Lucia
authors.initials: L
authors.lastname: Miligi
authors.forename: Milena
authors.initials: M
authors.lastname: Paglierani
authors.forename: Monica
authors.initials: M
authors.lastname: Pepi
authors.forename: Marco
authors.initials: M
authors.lastname: Santucci
mesh_terms: D000230:Adenocarcinoma / Q000209:etiology / Q000378:metabolism* / Q000473:pathology*; D002288:Adenocarcinoma, Mucinous / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D025601:Adenomatous Polyposis Coli Protein / Q000378:metabolism; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000378:metabolism; D000075389:DCC Receptor; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007414:Intestinal Neoplasms / Q000378:metabolism / Q000473:pathology; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D016273:Occupational Exposure; D010255:Paranasal Sinus Neoplasms / Q000209:etiology / Q000378:metabolism* / Q000473:pathology*; D011956:Receptors, Cell Surface / Q000378:metabolism; D016160:Retinoblastoma Protein / Q000378:metabolism; D046888:Tissue Array Analysis; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D025521:Tumor Suppressor Proteins / Q000378:metabolism; D060449:Wnt Signaling Pathway; D014934:Wood / Q000009:adverse effects; D051176:beta Catenin / Q000378:metabolism
chemical_list: C555337:APC protein, human; D025601:Adenomatous Polyposis Coli Protein; C495270:CTNNB1 protein, human; D019941:Cyclin-Dependent Kinase Inhibitor p16; D000075389:DCC Receptor; C501909:DCC protein, human; D011956:Receptors, Cell Surface; D016160:Retinoblastoma Protein; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins; D051176:beta Catenin