The present study suggests that (1) nearly 90% of AdCCs may have gene alterations of either MYB, MYBL1 or NFIB, suggesting the diagnostic utility of the FISH assay, (2) MYB or MYBL1 gene splits may be associated with local aggressiveness of the tumours and overexpression of MYC, which is one of the oncogenic MYB/MYBL1 targets and (3) MYC overexpression may be a risk factor for disease-free survival in AdCC.

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Aims Thymic carcinoma is rare and usually has a fatal outcome. Gene mutations in the epidermal growth factor receptor (EGFR) signalling pathway and TP53 have not been well analysed in thymic carcinoma. Methods and results We examined a large cohort of thymic carcinoma and thymoma type A/B3 and looked for gene mutations in the RAS family, EGFR, PIK3CA, AKT1, BRAF and TP53. Among 54 thymic carcinoma cases, RAS family mutations were detected in 10 cases, EGFR in two, PIK3CA in one, AKT1 in one, BRAF in none and TP53 in five. Among 33 thymoma type A/B3 cases, HRAS gene mutation were found in one, PIK3CA in two and AKT1 in one. All these mutations were those of missense type activating mutations. RAS family mutations were significantly more frequent in thymic carcinoma than in thymoma type A/B3 (P = 0.0461). A prognostic analysis focusing on thymic squamous cell carcinoma cases (n = 44) showed that the overall survival was significantly shorter in patients with EGFR pathway mutations (n = 9) than in those without in a univariate analysis (P = 0.0173). Subsequently, EGFR pathway mutations were selected as an independent factor for a poor overall survival in a multivariate analysis (P = 0.0389). Conclusions Mutations in the EGFR pathway and TP53 in thymic carcinoma may be frequent, and the EGFR pathway mutations may be associated with a poor prognosis in thymic squamous cell carcinoma patients. The therapeutic significance of gene mutations in thymic carcinoma should be further clarified.

Adenoid cystic carcinoma (AdCC), one of the most common salivary gland carcinomas, usually has a fatal outcome. Epidermal growth factor receptor (EGFR) pathway gene mutations are important in predicting a patient's prognosis and estimating the efficacy of molecular therapy targeting the EGFR pathway. In this study of salivary gland AdCC (SAdCC), we looked for gene mutations in EGFR, RAS family (KRAS, HRAS, and NRAS), PIK3CA, BRAF, and AKT1, using a highly sensitive single-base extension multiplex assay, SNaPshot. Out of 70 cases, EGFR pathway missense mutations were found in 13 (18.6%): RAS mutations in 10 (14.3%), EGFR in one (1.4%), and PIK3CA in 5 (7.1%). None of the cases showed an EGFR deletion by direct sequencing. Concurrent gene mutations were found in three cases (4.3%). EGFR pathway mutations were significantly associated with a shorter disease-free (p = 0.011) and overall survival (p = 0.049) and RAS mutations were as well; (p = 0.010) and (p = 0.024), respectively. The gene fusion status as determined by a FISH assay had no significant association with mutations of the genes involved in the EGFR pathway. In conclusion, EGFR pathway mutations, especially RAS mutations, may be frequent in SAdCC, and associated with a poor prognosis for the patient.