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.

Oncogenic drivers in 11q13 associated with prognosis and response to therapy in advanced oropharyngeal carcinomas

“…Particularly, gains of 11q13.2 (LRP5, PPP6R3 and SAPS3 genes) were exclusively detected in HPV-negative samples. Amplification of 11q13 is commonly reported in different tumors, including HNSCC [20,27,[35][36][37][38], particularly in HPV-negative tumors [39,40] and OPSCC [15]. Mutually exclusive amplifications of 11q13 (CCND1 and FADD) and 11q22 (BIRC2 and YAP1) were detected in HPV-negative HNSCC [27].…”

Genomic and Transcriptomic Characterization Links Cell Lines with Aggressive Head and Neck Cancers

“…Some of these chr alterations were observed in previous studies. Amplifications of 2q, 4q, 6p, and 6q were described in the invasive front area of laryngeal carcinoma and associated with aggressive tumor progression ( Ambrosio et al, 2013 ). The 6p21 region harbors oncogenes CCND3 , HMGA1 , cell cycle regulators CDKN1A , CDC5L , human leukocyte antigen ( HLA ), and cytidine deaminase gene APOBEC2 genes.…”

Integrated analysis revealing genome‑wide chromosomal copy number variation in supraglottic laryngeal squamous cell carcinoma

“…The chromosomal region of 3q, particularly 3q26-29, was demonstrated to be a defining feature of squamous cell carcinomas, with an ~75% predicted occurrence in HNSCC (25). Furthermore, gains of 11q13 and loss of 18q23 were positively associated with a poor outcome in patients with LSCC (23,26,27).…”