The Head & Neck Primary Sarcomatoid Carcinoma (HN PSC) is a rare sub-type of squamous cell carcinoma with poor prognosis. This study sought to describe the mutational profile of HN PSC using high-throughput genotyping technology Massarray, (Agena, Hamburg).
We included 45 patients with HN PSC. We used PCR mass spectrometry detection to establish the DNA mutation profiles of 72 samples from these patients (45 primary tumors, 5 metastatic cervical nodes and 22 non tumoral tissues) studying 214 mutations affecting 26 oncogenes and tumor suppressor genes.
In total, 33/45 (77.3%) patients were male and 31/45 (69%) were smokers. Median age was 60 years (range 13 – 93 years) and 28/45 (62.2%) were metastatic. The main tumor sites were oral cavities (31.1%) and larynx (28.1%). The predominant histological subtype was the pleomorphic form (66,7%). In the 72 tumors, 18 distinct somatic alterations were identified, 15 tumors (33%) harboring at least one mutation. The most frequent mutations were TP53 (11.1%), PIK3CA (8.9%), EPHA5 (4.4%), MET (4.4%), NOTCH1 (4.9%), NTRK2 (2.2%), BRAF (2.2%), JAK2 (2,2%), KRAS (2,2%) and NRF2 (2,2%). The presence of a mutation was not correlated with any clinical characteristic (age, sex, primary located site, cancer stage, tobacco and alcohol status). Only 1/45 (2.2%) tumor presented a targetable mutation with tyrosine kinase inhibitor (mutation BRAF). The mutational profile was identical between the local tumor site and the cervical node in 4/5 patients.
Our results demonstrated that HN PSC had a similar mutational profile of other HN carcinoma such as TP53, PIK3CA and NOTCH1 mutations. It reinforced the hypothesis of a single cell clone, which is acquired with different histological phenotypes by different, still unknown mechanisms involving epithelial to mesenchymal transition.
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V. Fallet: Travel, accommodations, expenses: GSK, BMS, Novartis, Boeringher Ingelheim. M. Wislez: Research funding: BMS, Boehringer Ingelheim; Consulting or advisory role: AstraZeneca, Roche, BMS, MSD, Novartis, Boehringer Ingelheim. All other authors have declared no conflicts of interest.