{"title":"EGFR mutations in sinonasal squamous neoplasms: Novel hotspot for exon 20 insertions.","authors":"Kirti Srivastava, Kavneet Kaur, Hitesh Verma, Deepali Jain, Alok Thakar, Aanchal Kakkar","doi":"10.1007/s00428-025-04070-0","DOIUrl":null,"url":null,"abstract":"<p><p>EGFR mutations and oncogenic high-risk (HR) HPV have been suggested to be mutually exclusive pathways in pathogenesis of sinonasal squamous neoplasms which include sinonasal papilloma and squamous cell carcinoma (SCC). In Indian patients, HR-HPV association is rare; however, there is no data on EGFR mutations in these tumors. One-hundred-eleven cases of sinonasal squamous neoplasms were interrogated for EGFR exon 19 and 20 mutations, including 48 inverted papillomas (IP), 15 SCC arising in the background of inverted papilloma (IP-SCC) and 48 de novo SCC. HR-HPV association was determined by p16 immunohistochemistry, followed by mRNA in situ hybridization (ISH) in all p16 positive and a subset of negative cases. Low-risk (LR)-HPV mRNA ISH was performed in all EGFR wild-type IP and IP-SCC. Among 94 cases with valid results (41 IP, 10 IP-SCC and 43 de novo SCC), EGFR mutations were identified in 24 (59%) IP, 4 (40%) IP-SCC and 15 (35%) de novo SCC. EGFR mutations were associated with nasal cavity location and non-keratinizing histology. All exon 20 insertions were located between residues 778 and 810. p16 immunopositivity was present in 18 cases, including 7 EGFR mutant ones. mRNA ISH identified HR-HPV in one p16 positive de novo SCC, which also had an EGFR mutation. LR-HPV was absent in all 34 cases tested. Thus, we identified EGFR exon 20 mutations at a novel hotspot in a sizeable number of sinonasal squamous neoplasms, both IPs and SCCs, suggesting that they play a significant role in their pathogenesis. Exon 19 mutations were uncommon.</p>","PeriodicalId":23514,"journal":{"name":"Virchows Archiv","volume":" ","pages":""},"PeriodicalIF":3.4000,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Virchows Archiv","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s00428-025-04070-0","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"PATHOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
EGFR mutations and oncogenic high-risk (HR) HPV have been suggested to be mutually exclusive pathways in pathogenesis of sinonasal squamous neoplasms which include sinonasal papilloma and squamous cell carcinoma (SCC). In Indian patients, HR-HPV association is rare; however, there is no data on EGFR mutations in these tumors. One-hundred-eleven cases of sinonasal squamous neoplasms were interrogated for EGFR exon 19 and 20 mutations, including 48 inverted papillomas (IP), 15 SCC arising in the background of inverted papilloma (IP-SCC) and 48 de novo SCC. HR-HPV association was determined by p16 immunohistochemistry, followed by mRNA in situ hybridization (ISH) in all p16 positive and a subset of negative cases. Low-risk (LR)-HPV mRNA ISH was performed in all EGFR wild-type IP and IP-SCC. Among 94 cases with valid results (41 IP, 10 IP-SCC and 43 de novo SCC), EGFR mutations were identified in 24 (59%) IP, 4 (40%) IP-SCC and 15 (35%) de novo SCC. EGFR mutations were associated with nasal cavity location and non-keratinizing histology. All exon 20 insertions were located between residues 778 and 810. p16 immunopositivity was present in 18 cases, including 7 EGFR mutant ones. mRNA ISH identified HR-HPV in one p16 positive de novo SCC, which also had an EGFR mutation. LR-HPV was absent in all 34 cases tested. Thus, we identified EGFR exon 20 mutations at a novel hotspot in a sizeable number of sinonasal squamous neoplasms, both IPs and SCCs, suggesting that they play a significant role in their pathogenesis. Exon 19 mutations were uncommon.
期刊介绍:
Manuscripts of original studies reinforcing the evidence base of modern diagnostic pathology, using immunocytochemical, molecular and ultrastructural techniques, will be welcomed. In addition, papers on critical evaluation of diagnostic criteria but also broadsheets and guidelines with a solid evidence base will be considered. Consideration will also be given to reports of work in other fields relevant to the understanding of human pathology as well as manuscripts on the application of new methods and techniques in pathology. Submission of purely experimental articles is discouraged but manuscripts on experimental work applicable to diagnostic pathology are welcomed. Biomarker studies are welcomed but need to abide by strict rules (e.g. REMARK) of adequate sample size and relevant marker choice. Single marker studies on limited patient series without validated application will as a rule not be considered. Case reports will only be considered when they provide substantial new information with an impact on understanding disease or diagnostic practice.