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Reduced FEZ1/LZTS1 Expression and Outcome Prediction in Lung Cancer

Departments of ¹ Pathology and ² Experimental Oncology, Units of ³ Medical Statistics and Biometry and ⁴ Thoracic Surgery, Istituto Nazionale Tumori, Milan, Italy; ⁵ Kimmel Cancer Center, Jefferson Medical College of Thomas Jefferson University, Philadelphia, Pennsylvania; ⁶ Division of Surgical Pathology, II Faculty of Medicine, University La Sapienza, Hospital Sant'Andrea, Rome, Italy; and ⁷ Baltimore Veterans' Administration Maryland Health Care System, University of Maryland Medical System and Johns Hopkins Medical Institutions, Baltimore, Maryland

Request for reprints: Gabriella Sozzi, Cytogenetics and Molecular Cytogenetics Unit, Department of Experimental Oncology, Istituto Nazionale Tumori, Via Venezian 1, 20133 Milan, Italy. Phone: 39-02-23902232; Fax: 39-02-23902764; E-mail: gabriella.sozzi{at}istitutotumori.mi.it.

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.

Key Words: Lung cancer • FEZ1/LZTS1 • cell cycle control • p34^cdc2

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