Distinctive Expression and Amplification of Genes at 11q13 in Relation to HPV Status with Impact on Survival in Head and Neck Cancer Patients

• Main Authors: Francisco Hermida-Prado, Sofía T. Menéndez, Pablo Albornoz-Afanasiev, Rocío Granda-Diaz, Saúl Álvarez-Teijeiro, M. Ángeles Villaronga, Eva Allonca, Laura Alonso-Durán, Xavier León, Laia Alemany, Marisa Mena, Nagore del-Rio-Ibisate, Aurora Astudillo, René Rodríguez, Juan P. Rodrigo, Juana M. García-Pedrero
• Format: Article
• Language: English
• Published: MDPI AG 2018-12-01
• Series: Journal of Clinical Medicine
• Subjects: head and neck squamous cell carcinoma; HPV; 11q13; gene amplification; immunohistochemistry
• Online Access: https://www.mdpi.com/2077-0383/7/12/501

Clear differences have been established between head and neck squamous cell carcinomas (HNSCC) depending on human papillomavirus (HPV) infection status. This study specifically investigated the status of the <i>CTTN</i>, <i>CCND1</i> and <i>ANO1</i> genes mapping at the 11q13 amplicon in relation to the HPV status in HNSCC patients. CTTN, CCND1 and ANO1 protein expression and gene amplification were respectively analyzed by immunohistochemistry and real-time PCR in a homogeneous cohort of 392 surgically treated HNSCC patients. The results were further confirmed using an independent cohort of 279 HNSCC patients from The Cancer Genome Atlas (TCGA). The impact on patient survival was also evaluated. <i>CTTN</i>, <i>CCND1</i> and <i>ANO1</i> gene amplification and protein expression were frequent in HPV-negative tumors, while absent or rare in HPV-positive tumors. Using an independent validation cohort of 279 HNSCC patients, we consistently found that these three genes were frequently co-amplified (28%) and overexpressed (39&#8315;46%) in HPV-negative tumors, whereas almost absent in HPV-positive tumors. Remarkably, these alterations (in particular CTTN and ANO1 overexpression) were associated with poor prognosis. Taken together, the distinctive expression and amplification of these genes could cooperatively contribute to the differences in prognosis and clinical outcome between HPV-positive and HPV-negative tumors. These findings could serve as the basis to design more personalized therapeutic strategies for HNSCC patients.