Pattern and clinical significance of cancer‐testis gene expression in head and neck squamous cell carcinoma

• Published in: International journal of cancer 2011-06, Vol.128 (11), p.2625-2634
• Main Authors: Cuffel, Cyril, Rivals, Jean‐Paul, Zaugg, Yannick, Salvi, Suzanne, Seelentag, Walter, Speiser, Daniel E., Liénard, Danielle, Monnier, Philippe, Romero, Pedro, Bron, Luc, Rimoldi, Donata
• Format: Article
• Language: English
• Subjects: Adult; Aged; Aged, 80 and over; Biological and medical sciences; Biomarkers, Tumor - genetics; Biomarkers, Tumor - metabolism; cancer‐testis antigens; Carcinoma, Squamous Cell - genetics; Carcinoma, Squamous Cell - metabolism; Female; gene expression; Head and Neck Neoplasms - genetics; Head and Neck Neoplasms - metabolism; head and neck squamous cell carcinoma (HNSCC); Humans; Immunoenzyme Techniques; immunotherapy; Male; Medical sciences; Middle Aged; Neoplasm Proteins - genetics; Neoplasm Proteins - metabolism; Otorhinolaryngology (head neck, general aspects and miscellaneous); Otorhinolaryngology. Stomatology; Prognosis; Prospective Studies; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger - genetics; RNA, Neoplasm - genetics; Tumors; tumor‐associated antigens
• ISSN: 0020-7136; 1097-0215
• DOI: 10.1002/ijc.25607

Cancer‐testis (CT) antigens comprise families of tumor‐associated antigens that are immunogenic in patients with various cancers. Their restricted expression makes them attractive targets for immunotherapy. The aim of this study was to determine the expression of several CT genes and evaluate their prognostic value in head and neck squamous cell carcinoma (HNSCC). The pattern and level of expression of 12 CT genes (MAGE‐A1, MAGE‐A3, MAGE‐A4, MAGE‐A10, MAGE‐C2, NY‐ESO‐1, LAGE‐1, SSX‐2, SSX‐4, BAGE, GAGE‐1/2, GAGE‐3/4) and the tumor‐associated antigen encoding genes PRAME, HERV‐K‐MEL, and NA‐17A were evaluated by RT‐PCR in a panel of 57 primary HNSCC. Over 80% of the tumors expressed at least 1 CT gene. Coexpression of three or more genes was detected in 59% of the patients. MAGE‐A4 (60%), MAGE‐A3 (51%), PRAME (49%) and HERV‐K‐MEL (42%) were the most frequently expressed genes. Overall, the pattern of expression of CT genes indicated a coordinate regulation; however there was no correlation between expression of MAGE‐A3/A4 and BORIS, a gene whose product has been implicated in CT gene activation. The presence of MAGE‐A and NY‐ESO‐1 proteins was verified by immunohistochemistry. Analysis of the correlation between mRNA expression of CT genes with clinico‐pathological characteristics and clinical outcome revealed that patients with tumors positive for MAGE‐A4 or multiple CT gene expression had a poorer overall survival. Furthermore, MAGE‐A4 mRNA positivity was prognostic of poor outcome independent of clinical parameters. These findings indicate that expression of CT genes is associated with a more malignant phenotype and suggest their usefulness as prognostic markers in HNSCC.