title: Chromosomal imbalances exclusively detected in invasive front area are associated with poor outcome in laryngeal carcinomas from different anatomical sites.
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.
authors.affiliation: Institute of Biosciences, UNESP-São Paulo State University, Botucatu, SP, Brazil.
authors.forename: Eliane Papa
authors.initials: EP
authors.lastname: Ambrosio
authors.forename: Cássia Gisele Terrassani
authors.initials: CG
authors.lastname: Silveira
authors.forename: Sandra Aparecida
authors.initials: SA
authors.lastname: Drigo
authors.forename: Vivian de Souza
authors.initials: Vde S
authors.lastname: Sacomano
authors.forename: Miriam Coelho
authors.initials: MC
authors.lastname: Molck
authors.forename: Rafael Malagoli
authors.initials: RM
authors.lastname: Rocha
authors.forename: Maria Aparecida Custódio
authors.initials: MA
authors.lastname: Domingues
authors.forename: Fernando Augusto
authors.initials: FA
authors.lastname: Soares
authors.forename: Luiz Paulo
authors.initials: LP
authors.lastname: Kowalski
authors.forename: Silvia Regina
authors.initials: SR
authors.lastname: Rogatto
mesh_terms: D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000556:secondary; D002869:Chromosome Aberrations; D002877:Chromosomes, Human; D055028:Comparative Genomic Hybridization; D019938:Cyclin D1 / Q000378:metabolism; D005260:Female; D018628:Gene Dosage; D006801:Humans; D007150:Immunohistochemistry; D007822:Laryngeal Neoplasms / Q000235:genetics* / Q000473:pathology; D061346:Laser Capture Microdissection; D019656:Loss of Heterozygosity; D008207:Lymphatic Metastasis; D008297:Male; D053842:Microsatellite Instability; D018895:Microsatellite Repeats; D008875:Middle Aged; D046888:Tissue Array Analysis
chemical_list: C530104:CCND1 protein, human; D019938:Cyclin D1