PMID- 23749487 OWN - NLM STAT- MEDLINE DCOM- 20131126 LR - 20211021 IS - 1423-0380 (Electronic) IS - 1010-4283 (Linking) VI - 34 IP - 5 DP - 2013 Oct TI - Chromosomal imbalances exclusively detected in invasive front area are associated with poor outcome in laryngeal carcinomas from different anatomical sites. PG - 3015-26 LID - 10.1007/s13277-013-0866-0 [doi] AB - 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. FAU - Ambrosio, Eliane Papa AU - Ambrosio EP AD - Institute of Biosciences, UNESP-Sao Paulo State University, Botucatu, SP, Brazil. FAU - Silveira, Cassia Gisele Terrassani AU - Silveira CG FAU - Drigo, Sandra Aparecida AU - Drigo SA FAU - Sacomano, Vivian de Souza AU - Sacomano Vde S FAU - Molck, Miriam Coelho AU - Molck MC FAU - Rocha, Rafael Malagoli AU - Rocha RM FAU - Domingues, Maria Aparecida Custodio AU - Domingues MA FAU - Soares, Fernando Augusto AU - Soares FA FAU - Kowalski, Luiz Paulo AU - Kowalski LP FAU - Rogatto, Silvia Regina AU - Rogatto SR LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20130608 PL - Netherlands TA - Tumour Biol JT - Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine JID - 8409922 RN - 0 (CCND1 protein, human) RN - 136601-57-5 (Cyclin D1) SB - IM MH - Carcinoma, Squamous Cell/*genetics/secondary MH - *Chromosome Aberrations MH - Chromosomes, Human MH - Comparative Genomic Hybridization MH - Cyclin D1/metabolism MH - Female MH - Gene Dosage MH - Humans MH - Immunohistochemistry MH - Laryngeal Neoplasms/*genetics/pathology MH - Laser Capture Microdissection MH - Loss of Heterozygosity MH - Lymphatic Metastasis MH - Male MH - Microsatellite Instability MH - Microsatellite Repeats MH - Middle Aged MH - Tissue Array Analysis EDAT- 2013/06/12 06:00 MHDA- 2013/12/16 06:00 CRDT- 2013/06/11 06:00 PHST- 2013/02/27 00:00 [received] PHST- 2013/05/13 00:00 [accepted] PHST- 2013/06/11 06:00 [entrez] PHST- 2013/06/12 06:00 [pubmed] PHST- 2013/12/16 06:00 [medline] AID - 10.1007/s13277-013-0866-0 [doi] PST - ppublish SO - Tumour Biol. 2013 Oct;34(5):3015-26. doi: 10.1007/s13277-013-0866-0. Epub 2013 Jun 8.