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

Author(s)

Ambrosio, Eliane Papa ^{[1, 2]} ; Terrassani Silveira, Cassia Gisele ^{[1, 2]} ; Drigo, Sandra Aparecida ^{[1, 3]} ; Sacomano, Vivian de Souza ^[2] ; Molck, Miriam Coelho ^{[1, 2]} ; Rocha, Rafael Malagoli ^[4] ; Custodio Domingues, Maria Aparecida ^[5] ; Soares, Fernando Augusto ^[4] ; Kowalski, Luiz Paulo ^{[6, 7]} ; Rogatto, Silvia Regina ^{[1, 8]}

Affiliation

^[1] AC Camargo Canc Ctr, CIPE, Int Res Ctr, BR-0150801 Liberdade Sao Paulo, SP - Brazil

^[2] UNESP Sao Paulo State Univ, Inst Biosci, Botucatu, SP - Brazil

^[3] UNESP Sao Paulo State Univ, Fac Med, Dept Urol, Botucatu, SP - Brazil

^[4] AC Camargo Hosp, Dept Pathol, Sao Paulo - Brazil

^[5] UNESP Sao Paulo State Univ, Dept Pathol, Botucatu, SP - Brazil

^[6] AC Camargo Hosp, Dept Head & Neck Surg & Otorhinolaryngol, Sao Paulo - Brazil

^[7] AC Camargo Hosp, Natl Inst Oncogen INCITO, Sao Paulo - Brazil

^[8] Hosp AC Camargo Fund Antonio Prudente, NeoGene Lab Fundacao Antonio Prudente, BR-01508010 Sao Paulo - Brazil

• Document type: Journal article
• Source: TUMOR BIOLOGY; v. 34, n. 5, p. 3015-3026, OCT 2013.
• Web of Science Citations: 4

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. (AU)

• FAPESP's process: 08/57887-9 - National Institute of Oncogenomics
• Grantee: Luiz Paulo Kowalski
• Support Opportunities: Research Projects - Thematic Grants