Chromosomal imbalances exclusively detected in invasive front area are associated with poor outcome in laryngeal carcinomas from different anatomical sites
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Laryngeal squamous cell carcinoma (LSCC) is a malignant neoplasm exhibiting aggressive phenotype, high recurrence rate, and risk of developing second primary tumors. Current evidence suggests that cells in the invasive front of carcinomas have different molecular profiles compared to those in superficial areas. This study aimed to identify candidate genes in the invasive front and superficial cells from laryngeal carcinomas that would be useful as molecular markers. Invasive front and tumor surface cells of 32 LSCC were evaluated by high-resolution comparative genomic hybridization. Both CCND1 copy number gains and cyclin D1 protein expression were evaluated to confirm gains of 11q13.3. Losses of 3q26.2-q29 and 18q23 were confirmed by loss of heterozygosity analysis. The most frequent chromosomal alterations observed only in invasive front cells involved gains of 1p, 4q, and 9p and losses of 3p, 11p, 12p, 13q, 17q, 18p, 19q, 20q, 21q, and Xp. Gains of 11q13 were detected in both components from glottis and supraglottis but only in invasive front cells from transglottic tumors. Fluorescence in situ hybridization confirmed gains of CCND1/CPE11 in a subset of cases. In supraglottic tumors, cyclin D1 positivity was associated with distant metastasis (P = 0.0018) and with decreased disease-free survival (P = 0.042). Loss of heterozygosity at 3q26.2 and 18q23 were associated with lymph node involvement (P = 0.055) and worsened prognosis, respectively. In conclusion, this study revealed regions that could be targeted in the search for molecular markers in LSCC. Cyclin D1 may be useful as a prognostic marker in supraglottic tumors.
KeywordsLaryngeal carcinomas Comparative genomic hybridization Invasive front Molecular markers Chromosomal imbalances
The authors would like to thank Francine Blumental de Abreu and Hellen Kuasne for their technical assistance. The authors also express their gratitude to Dr Fabiola Encinas Rosa and Dr Claudia A Rainho for their many helpful suggestions throughout the manuscript's preparation. This work was supported by grants from the National Institute of Science and Technology in Oncogenomics (INCITO—Fundação de Amparo à Pesquisa do Estado de São Paulo—FAPESP 2008/57887-9 and Conselho Nacional de Desenvolvimento Científico e Tecnológico—CNPq 573589/08-9) and FAPESP 07/52265-7.
Conflicts of interest
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