Multiple genetic copy number alterations in oral squamous cell carcinoma: study of MYC, TP53, CCDN1, EGFR and ERBB2 status in primary and metastatic tumours

• Published in: British journal of dermatology (1951) Vol. 163; no. 5; pp. 1028 - 1035
• Main Authors: Martín-Ezquerra, G., Salgado, R., Toll, A., Gilaberte, M., Baró, T., Alameda Quitllet, F., Yébenes, M., Solé, F., Garcia-Muret, M., Espinet, B., Pujol, R.M.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.11.2010; Wiley-Blackwell
• Subjects: Adult; Aged; Aged, 80 and over; Benign; Biological and medical sciences; Biomarkers, Tumor - genetics; Biomarkers, Tumor - metabolism; Biopsy; carcinogenesis; carcinoma; Carcinoma, Squamous Cell - genetics; CCND1; copy number; cyclin D1; Cyclin D1 - genetics; Cyclin D1 - metabolism; Dermatology; EGFR; Epidermal growth factor receptors; ErbB-2 protein; ERBB2; Female; Fluorescence in situ hybridization; Gene Dosage; Genes, p53 - genetics; Humans; Immunohistochemistry; Inflammation; Invasiveness; Lichen planus; Lymph Nodes; Male; Medical sciences; Metastases; Middle Aged; Mouth Neoplasms - genetics; Mucosa; Myc protein; Neoplasm Metastasis - genetics; Oncogenes; Oncogenes - genetics; Oral cavity; oral squamous cell carcinoma; Otorhinolaryngology. Stomatology; p53 protein; Protein status; Proto-Oncogene Proteins c-myc - genetics; Proto-Oncogene Proteins c-myc - metabolism; Receptor, Epidermal Growth Factor - genetics; Receptor, Epidermal Growth Factor - metabolism; Receptor, ErbB-2 - genetics; Receptor, ErbB-2 - metabolism; Reviews; squamous cell; TP53; Transformation; Tumor suppressor genes; Tumorigenesis; Tumors; Upper respiratory tract, upper alimentary tract, paranasal sinuses, salivary glands: diseases, semeiology; Multiple; Stomatology; Dermatology; Malignant tumor; Oral squamous cell carcinoma; Metastasis; Carcinogenesis; CCND 1; EGFR; carcinoma; squamous cell; ERBB2; Oral cavity disease; Metastatic; TP53; Cancer
• ISSN: 0007-0963; 1365-2133
• DOI: 10.1111/j.1365-2133.2010.09947.x

Summary Background  Oncogenesis in the oral cavity is believed to result from genetic alterations that cause a stepwise transformation of the mucosa to invasive carcinoma. In oral squamous cell carcinoma (OSCC) multiple cytogenetic abnormalities have been reported, but their practical significance remains uncertain. Objective  To evaluate the usefulness of the assessment of CCND1, MYC, EGFR, ERBB2 and TP53 in OSCC and lymph node metastases. Methods  Fifty‐one consecutive samples of OSCC, nine lymph node biopsies showing metastatic spread from OSCC, 16 biopsies diagnosed as oral leucoplakia (OLK), 13 samples corresponding to oral lichen planus (OLP) and 14 samples from normal oral mucosa were included in the study. Clinical and histopathological characteristics were reviewed. The genetic and protein status of the CCND1, MYC, EGFR, ERBB2 oncogenes and the TP53 tumour suppressor gene were assessed by fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC). The obtained results were compared with the clinical characteristics and the outcome of the OSCCs. Results  TP53 gene losses and MYC, ERBB2, CCND1 and EGFR copy number gains and amplifications were detected in a higher proportion in OSCC and lymph node samples than in OLK and OLP samples (P < 0·005). Overexpression of p53, Myc, Cyclin D1, c‐erbB‐2 and epidermal growth factor receptor (EGFR) was more prevalent in malignant samples than benign samples (P < 0·05). Correlation between FISH and IHC results was demonstrated in MYC, EGFR and CCND1 studies. The presence of two or more genetic abnormalities in the studied loci was exclusively detected in primary and metastatic OSCC. Conclusions  In our series, genetic abnormalities in TP53, MYC, CCND1, ERBB2 and EGFR detected by FISH were absent in inflammatory lesions, infrequent in precursor lesions and common in tumoral lesions. Evaluation of the genetic status of TP53, MYC, CCND1, ERBB2 and EGFR may be an additional diagnostic tool in distinguishing benign from malignant oral lesions in histopathologically challenging cases.