Abstract
Oral squamous cell cancer (OSCC) is a common malignancy attributed to use of chewing smokeless tobacco and smoking. Most of the targeted strategies are based on EGFR expression and mutation; however, none of them has shown significant improvement in survival and response rates. We carried out this study to evaluate mutational profile of tobacco associated oral carcinoma with special emphasis on EGFR and its downstream events.Patients and methodsA total of 46 histologically proven cases were recruited between January 2017 and January 2019. Apart from detailed clinical and histological studies, the paraffin-embedded tissue was submitted for expression of 50 genes using Next Generation Sequencing using Ion Ampliseq Cancer Hotspot Panel v2.ResultsThe mean age of patients was 47.8 ± 10.9 years. Majority had tumors on buccal mucosa (24) and tongue (13). Nineteen of these tumors were larger than 4 cm, and 5 had adjacent site involvement. Thirty one were node positive. TP53 mutations were commonest seen in 19 followed by CDKN2A in 11, HRAS in 8, PIK3CA in 3, SMARCB1 in 2, and KIT, EGFR, BRAF, STK11, ABL1, RB1 in one case each. Concomitant TP53 mutation was identified with other mutations like CDKN2A, HRAS, KIT, PIK3CA, STK11, SMARCB1, ABL1, and RB1 making tobacco-associated OSCC as a heterogeneous mutational tumor with multiple events. A patient with TP53 mutations has poor disease free survival (47.4 vs 63% p = 0.17); however, this was not statistically significant.ConclusionThe study shows a heterogeneous mutational spectrum with multiple mutational events in OSCC. The low EGFR mutation rates and higher mutations in EGFR downstream pathways including that in TP53 and HRAS suggest that anti EGFR strategies may not succeed in these tumors and newer agents and therapeutic combinations need to be tried.
Highlights
Oral squamous cell cancer (OSCC) is the most common malignancy among males in India and the eighth most common cancer worldwide [1]
The low EGFR mutation rates and higher mutations in EGFR downstream pathways including that in TP53 and HRAS suggest that anti EGFR strategies may not succeed in these tumors and newer agents and therapeutic combinations need to be tried
EGFR is a member of receptor protein tyrosine kinase family with 42–80% over expression in head neck squamous cell carcinoma (HNSCC), whereas EGFR gene
Summary
Oral squamous cell cancer (OSCC) is the most common malignancy among males in India and the eighth most common cancer worldwide [1]. EGFR is a member of receptor protein tyrosine kinase family with 42–80% over expression in head neck squamous cell carcinoma (HNSCC), whereas EGFR gene. Afatinib (selective EGFR and HER2 inhibitor), erlotinib (an oral reversible EGFR TKI), and gefitinib (a reversible EGFR TKI) have been used in cases with EGFR exon 19 deletions or exon 21 (L858R) substitution mutations as detected by an FDA-approved test. Vamurafenib (an oral selective inhibitor of BRAF kinase V600E oncogene) in unresectable and metastatic melanoma with the BRAFV600E mutation have been recently approved [11,12,13,14,15,16]. Still mono therapy with TKI’s has only modest activity in EGFR mutated HNSCC [17]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
