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Tumor Biology

, Volume 34, Issue 5, pp 3015–3026 | Cite as

Chromosomal imbalances exclusively detected in invasive front area are associated with poor outcome in laryngeal carcinomas from different anatomical sites

  • Eliane Papa Ambrosio
  • Cássia Gisele Terrassani Silveira
  • Sandra Aparecida Drigo
  • Vivian de Souza Sacomano
  • Miriam Coelho Molck
  • Rafael Malagoli Rocha
  • Maria Aparecida Custódio Domingues
  • Fernando Augusto Soares
  • Luiz Paulo Kowalski
  • Silvia Regina Rogatto
Research Article

Abstract

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.

Keywords

Laryngeal carcinomas Comparative genomic hybridization Invasive front Molecular markers Chromosomal imbalances 

Notes

Acknowledgments

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

None

Supplementary material

13277_2013_866_MOESM1_ESM.docx (23 kb)
Online Resource 1 Microsatellite markers: location and primer sets. (DOCX 23.0 kb)
13277_2013_866_MOESM2_ESM.doc (44 kb)
Online Resource 2 Differential chromosomal gains and losses in invasive front and surface cells detected by HR-CGH. (DOC 44.5 kb)
13277_2013_866_MOESM3_ESM.doc (162 kb)
Online Resource 3 Comparison between cyclin D1 expression in unpaired LSCC samples and clinical and histopathological data. (DOC 162 kb)

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Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2013

Authors and Affiliations

  • Eliane Papa Ambrosio
    • 1
    • 2
  • Cássia Gisele Terrassani Silveira
    • 1
    • 2
  • Sandra Aparecida Drigo
    • 2
    • 3
  • Vivian de Souza Sacomano
    • 1
  • Miriam Coelho Molck
    • 1
    • 2
  • Rafael Malagoli Rocha
    • 5
  • Maria Aparecida Custódio Domingues
    • 4
  • Fernando Augusto Soares
    • 5
  • Luiz Paulo Kowalski
    • 6
  • Silvia Regina Rogatto
    • 2
    • 7
  1. 1.Institute of BiosciencesUNESP-São Paulo State UniversityBotucatuBrazil
  2. 2.International Research Center - CIPE, A.C. Camargo Cancer CenterLiberdade ­ São PauloBrazil
  3. 3.Department of Urology, Faculty of MedicineUNESP-São Paulo State UniversityBotucatuBrazil
  4. 4.Department of PathologyUNESP-São Paulo State UniversityBotucatuBrazil
  5. 5.Department of PathologyAC Camargo HospitalSão PauloBrazil
  6. 6.Department of Head and Neck Surgery and Otorhinolaryngology and National Institute of Oncogenomics (INCITO)A.C. Camargo HospitalSão PauloBrazil
  7. 7.NeoGene Laboratory Fundação Antonio PrudenteHospital A.C. CamargoSão PauloBrazil

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