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Reduced FEZ1/LZTS1 expression and outcome prediction in lung cancer
Daisuke Nonaka1, Alessandra Fabbri, Luca Roz
1Department of Pathology, Istituto Nazionale Tumori, Milan, Italy.
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.
Insights
Loss of FEZ1 protein expression is common in lung cancer, particularly in higher-grade tumors. This suggests FEZ1 may be a crucial tumor suppressor and a potential prognostic marker for lung cancer patients.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Chromosomal deletions in lung cancer often target tumor suppressor genes.
- Chromosome 8p22 deletions are frequent in lung cancer, implicating candidate genes like FEZ1/LZTS1.
- FEZ1/LZTS1 is known to suppress cancer cell growth and regulate mitosis, and is inactivated in various other cancers.
Purpose of the Study:
- To investigate the role of the FEZ1 gene in lung cancer development and progression.
- To analyze the expression levels of FEZ1 protein in primary lung cancer specimens.
- To determine if FEZ1 expression correlates with tumor characteristics or patient outcomes.
Main Methods:
- Immunohistochemistry was used to assess FEZ1 protein expression.
- 103 primary lung cancer specimens were analyzed, including non-small cell lung cancers (NSCLC) and small cell lung cancers (SCLC).
- Statistical analysis was performed to correlate FEZ1 expression with tumor grade and mortality rates.
Main Results:
- Absence or significant reduction of FEZ1 protein expression was observed in 26% and 42% of lung cancer cases, respectively.
- Loss of FEZ1 expression showed a positive association with higher tumor grading (P = 0.0345).
- A trend suggested a reduced mortality rate in patients with strong FEZ1 expression.
Conclusions:
- FEZ1 plays a significant role in lung cancer, likely as a tumor suppressor.
- Reduced or absent FEZ1 expression is linked to more aggressive tumor characteristics.
- FEZ1 protein expression may serve as a novel prognostic indicator for lung cancer.