Oncogene amplification pattern in adenoid cystic carcinoma of the salivary glands.
The aim of the present study was the search of molecular alterations (oncogene amplification or protein overexpression) that could have an impact on the outcome of ACC patients. For this purpose, paraffin-embedded tissue samples of primary ACC of 24 patients were collected. Oncogenic amplification status of six targets previously described to be involved in human carcinogenesis (ERBB1, KIT, PIK3CA, CCND1, MYC and MDM2) were studied by a PCR-based semiquantitative approach. C-Kit, cyclin D1 and EGFR protein levels were immunohistochemically assessed. ERBB1, CCND1 and PIK3CA were frequent targets of oncogene amplification (67, 46 and 38%, respectively). C-Kit and cyclin D1 were overexpressed in 57 and 82%, respectively. CCND1 amplification was associated with advanced tumour stage and ERBB1 amplification to distant metastasis. ERBB1/CCND1/PIK3CA coamplification was the most consistently observed pattern (29%). The cases with this amplification pattern presented a reduced survival. This study points to the importance of ERBB1, CCND1 and PIK3CA oncogenic amplification status in ACC carcinogenesis.
Servicio de Otorrinolaringología, Hospital Universitario Central de Asturias (HUCA), Asturias, Spain.
Guadalupe
G
Sequeiros-Santiago
Dario
D
García-Carracedo
Manuel F
MF
Fresno
Carlos
C
Suarez
Juan P
JP
Rodrigo
M Victoria
MV
Gonzalez
D000293:Adolescent; D000328:Adult; D000368:Aged; D003528:Carcinoma, Adenoid Cystic / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D019938:Cyclin D1 / Q000096:biosynthesis / Q000235:genetics; D066246:ErbB Receptors / Q000096:biosynthesis / Q000235:genetics; D005260:Female; D005784:Gene Amplification; D019940:Genes, bcl-1; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D009857:Oncogenes; D019009:Proto-Oncogene Proteins c-kit / Q000096:biosynthesis / Q000235:genetics; D012468:Salivary Gland Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D015996:Survival Rate; D055815:Young Adult
D019938:Cyclin D1; D066246:ErbB Receptors; D019009:Proto-Oncogene Proteins c-kit