Detection of MAPK/ERK pathway proteins and KRAS mutations in adenomatoid odontogenic tumors

• Published in: Oral diseases 2019-03, Vol.25 (2), p.481-487
• Main Authors: Bologna‐Molina, Ronell, Ogawa, Ikuko, Mosqueda‐Taylor, Adalberto, Takata, Takashi, Sánchez‐Romero, Celeste, Villarroel‐Dorrego, Mariana, Takeda, Yasunori, Mikami, Toshinari
• Format: Article
• Language: English
• Subjects: adenomatoid odontogenic tumor; Adolescent; Adult; Ameloblastoma - genetics; Ameloblastoma - metabolism; Cancer; Child; Child, Preschool; Dentistry; Epidermal growth factor receptors; ErbB Receptors - metabolism; ERK pathway; Extracellular signal-regulated kinase; Extracellular Signal-Regulated MAP Kinases - metabolism; Female; Humans; Immunohistochemistry; K-Ras protein; KRAS; Male; MAP kinase; MAP Kinase Signaling System; MAPK; Metabolic pathways; Middle Aged; Missense mutation; Mutation; Mutation hot spots; next‐generation sequencing; Nucleotide sequence; Odontogenic tumors; Paraffin; Proteins; Proto-Oncogene Proteins B-raf - metabolism; Proto-Oncogene Proteins c-raf - metabolism; Proto-Oncogene Proteins p21(ras) - genetics; Proto-Oncogene Proteins p21(ras) - metabolism; Signal transduction; Tumor cells; Tumorigenesis; Tumors; Young Adult
• ISSN: 1354-523X; 1601-0825
• DOI: 10.1111/odi.12989

Objective This study aimed to assess the frequency of KRAS mutation and its association with the presence of the MAPK/ERK signaling pathway proteins in adenomatoid odontogenic tumors. Study Design Paraffin‐embedded tissue samples from nine cases of adenomatoid odontogenic tumor were used. Genomic DNA was extracted from each sample; in one case, genetic mutations in 50 cancer‐associated genes were examined by next‐generation sequencing. Hotspot mutations in the RAS family were analyzed by Luminex assay using the remaining eight cases. Subsequently, immunohistochemistry for KRAS, CRAF, BRAF, EGFR, ERK, MEK, and BRAFV600E was performed. Results A KRAS G12D missense mutation was detected in the DNA sequence of the tumor cells, but it was not detected in the stromal tissue. KRAS G12V and KRAS G12R mutations were detected in two and four cases, respectively. For immunohistochemistry, all the cases were EGFR, KRAS, BRAF, CRAF positive, one case was ERK negative,and one case was MEK and ERK negative, all the other remaining cases were MEK and ERK positive. Conclusion KRAS mutation at codon 12 and the presence of MAPK/ERK pathway proteins were detected suggesting their association with tumorigenesis of adenomatoid odontogenic tumors.