title: Reduced FEZ1/LZTS1 expression and outcome prediction in lung cancer.
abstract: Chromosomal deletions are often observed in lung cancers suggesting that inactivation of tumor suppressor genes plays an important role in the development of this neoplasm. The region around chromosome 8p22 is a frequent and early target of these deletions and has therefore been investigated for the presence of candidate genes. The FEZ1/LZTS1 gene, located at 8p22, is inactivated in many cancers with 8p deletions, including prostate, esophageal, gastric, bladder, and breast cancer and the Fez1 protein has been shown to suppress growth of cancer cells and to regulate mitosis. To elucidate the role of FEZ1 in lung cancer, we have analyzed its expression by immunohistochemistry in 103 primary lung cancer specimens including 98 non-small cell lung cancers (57 adenocarcinomas, 32 squamous cell carcinomas, 7 large cell carcinomas, and 2 others) and five small cell carcinomas. Absence of Fez1 protein expression was observed in 27 cases (26%) and additional 43 cases (42%) showed strong reduction in immunoreactivity. There was a positive association between loss of FEZ1 expression and tumor grading (P = 0.0345) and a tendency toward a reduction in the mortality rate in subjects with strong FEZ1 expression. Overall, these data indicate an important role for FEZ1 in lung cancer and suggest the possibility that it may serve as a novel prognostic indicator.
authors.affiliation: Department of Pathology, Istituto Nazionale Tumori, Milan, Italy.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Nonaka
authors.forename: Alessandra
authors.initials: A
authors.lastname: Fabbri
authors.forename: Luca
authors.initials: L
authors.lastname: Roz
authors.forename: Luigi
authors.initials: L
authors.lastname: Mariani
authors.forename: Andrea
authors.initials: A
authors.lastname: Vecchione
authors.forename: G William
authors.initials: GW
authors.lastname: Moore
authors.forename: Luca
authors.initials: L
authors.lastname: Tavecchio
authors.forename: Carlo M
authors.initials: CM
authors.lastname: Croce
authors.forename: Gabriella
authors.initials: G
authors.lastname: Sozzi
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000096:biosynthesis* / Q000235:genetics; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D004268:DNA-Binding Proteins / Q000096:biosynthesis* / Q000235:genetics; D005260:Female; D016147:Genes, Tumor Suppressor; D006801:Humans; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009419:Nerve Tissue Proteins; D011379:Prognosis; D012189:Retrospective Studies; D025521:Tumor Suppressor Proteins / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; C528597:FEZ1 protein, human; C118711:LZTS1 protein, human; D009419:Nerve Tissue Proteins; D025521:Tumor Suppressor Proteins