title: WWOX expression in different histologic types and subtypes of non-small cell lung cancer.
abstract: OBJECTIVE
  Non-small cell lung cancer (NSCLC) has heterogeneous histopathologic classification and clinical behavior and very low survival rate. WWOX (WW domain-containing oxidoreductase) is a tumor suppressor gene, and its expression is altered in several cancers. The purpose of this study is to better define the role of WWOX in NSCLC tumorigenesis and progression by determining its pathogenetic and prognostic significance.
  
  
  METHODS
  WWOX protein expression was evaluated by immunohistochemistry in 170 patients with NSCLC (101 squamous cell carcinomas, 66 adenocarcinomas, 3 large cell carcinomas) and was correlated with histopathologic (histotype, subtype, grade, tumor-node-metastasis, stage, index of cell proliferation Ki67/MIB1) and clinical (age, gender, local recurrences, distant metastases, overall survival, and disease-free survival) characteristics.
  
  
  RESULTS
  WWOX expression was absent/reduced in 84.9% of NSCLCs, whereas it was normal in 80.5% of adjacent normal lung tissues. WWOX expression was strongly associated with tumor histology (P=1.1x10(-5)) and histologic grade (P=0.0081): the percentage of cases with absent/strongly reduced WWOX expression was higher in squamous cell carcinomas and in poorly differentiated tumors. Regarding adenocarcinoma, bronchioloalveolar pattern showed normal WWOX expression in 62.5% of the cases, whereas in solid and acinar patterns, a prevalence of cases with absent/very low WWOX expression was observed (79.2% and 50%, respectively). Finally, weak WWOX staining intensity was related to the high index of cell proliferation (P=0.0012).
  
  
  CONCLUSIONS
  Our results suggest that the loss of WWOX expression plays different roles in tumorigenesis of distinct histotypes and subtypes of NSCLC and is related to high aggressiveness (G3; high proliferating activity) of tumors.
authors.affiliation: Department of Surgery, Division of Anatomic Pathology and Cardio-Thoracic Surgery, University of Pisa and Scuola Normale Superiore and Istituto Nazionale di Fisica Nucleare, Section of Pisa, Pisa, Italy. valentina.donati@gmail.com
authors.forename: Valentina
authors.initials: V
authors.lastname: Donati
authors.forename: Gabriella
authors.initials: G
authors.lastname: Fontanini
authors.forename: Matteo
authors.initials: M
authors.lastname: Dell'Omodarme
authors.forename: Maria Cristina
authors.initials: MC
authors.lastname: Prati
authors.forename: Simona
authors.initials: S
authors.lastname: Nuti
authors.forename: Marco
authors.initials: M
authors.lastname: Lucchi
authors.forename: Alfredo
authors.initials: A
authors.lastname: Mussi
authors.forename: Muller
authors.initials: M
authors.lastname: Fabbri
authors.forename: Fulvio
authors.initials: F
authors.lastname: Basolo
authors.forename: Carlo Maria
authors.initials: CM
authors.lastname: Croce
authors.forename: Rami Ishaq
authors.initials: RI
authors.lastname: Aqeilan
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002289:Carcinoma, Non-Small-Cell Lung / Q000378:metabolism* / Q000473:pathology; D049109:Cell Proliferation; D018450:Disease Progression; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D010088:Oxidoreductases / Q000096:biosynthesis* / Q000737:chemistry; D011379:Prognosis; D013997:Time Factors; D025521:Tumor Suppressor Proteins / Q000096:biosynthesis* / Q000737:chemistry; D000074584:WW Domain-Containing Oxidoreductase
chemical_list: D025521:Tumor Suppressor Proteins; D010088:Oxidoreductases; D000074584:WW Domain-Containing Oxidoreductase; C486071:WWOX protein, human