EGFR Exon 20 Insertion Mutations in Sinonasal Squamous Cell Carcinoma

Pacini, Laura; Cabal, Virginia N.; Hermsen, Mario; Huang, Paul H.

doi:10.3390/cancers14020394

Cited by 7 publications

(7 citation statements)

References 107 publications

(184 reference statements)

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“…17,18 There is no evidence in clinical trials of SNCtargeted therapy, but there were some effective in vitro experiments of exon 20 mutation SNC by epidermal growth factor receptor gene (EGFR) exon 20 inhibitor targeted therapy, neratinib, which sparked a debate about the viability of SNC treatment. 19,20 On the other hand, the treatments in OC, OPC, and LC have gained potential to use targeted therapy and immunotherapy, such as nivolumab and cetuximab. Nivolumab and cetuximab are monoclonal antibodybased therapies that target Programmed death 1 (PD-1) and EGFR, respectively.…”

Section: Discussionmentioning

confidence: 99%

High 4-1BB Expression in PBMCs and Tumor Infiltrating Lymphocytes (TILs) in Patients with Head and Neck Squamous Cell Carcinoma

et al. 2023

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Objective 4-1BB is a costimulatory immune-activating molecule. Increased amounts of this protein have previously been found in the plasma of patients with oropharyngeal and oral cancer. Here, we focused on this molecule that functions as part of the immune system. We investigated 4-1BB in the peripheral blood mononuclear cells (PBMCs) and tumor infiltrating lymphocytes (TILs) of patients with head and neck squamous cell cancer (HNSCC). Materials and Methods The expression level of 4-1BB in the PBMCs was determined using real-time polymerase chain reaction (PCR). The TIMER (Tumor Immune Estimation Resource) web server was utilized to approximate the 4-1BB level in HNSCC TILs. Moreover, 4-1BB immunohistochemistry (IHC) was used to validate TILs in four organs of HNSCC, including oral cancer (OC), oropharyngeal cancer (OPC), sinonasal cancer (SNC), and laryngeal cancer (LC), in both the tumor area and adjacent normal epithelium. The difference in 4-1BB expression levels in various groups was assessed using a Kruskal-Wallis test and an independent sample t-test. Results The level of 4-1BB expression in PBMCs was highest in OPC, followed by OC and healthy controls (HC). Significant differences were discovered between HC and OPC and between OC and OPC. Bioinformatics revealed a substantial correlation between 4-1BB expression level and lymphocyte infiltration in HNSCC, including B cells, CD8+ T cells, and CD4+ T cells. IHC validation in HNSCC tissue revealed that the average number of 4-1BB positive TILs in all four HNSCC subtypes was considerably greater than the number of lymphocytes seen in adjacent normal tissue. Interestingly, the number of lymphocytes that were 4-1BB positive increased in relation to the TIL level. Conclusion A higher number of 4-1BB expression levels were found in the PBMCs and TILs of HNSCC patients, implying that 4-1BB may be a promising approach for HNSCC patients to improve their immune function. It is important to study and create a treatment that uses 4-1BB medicine as well as existing drugs.

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Section: Discussionmentioning

confidence: 99%

High 4-1BB Expression in PBMCs and Tumor Infiltrating Lymphocytes (TILs) in Patients with Head and Neck Squamous Cell Carcinoma

et al. 2023

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“…Considering that smoking and occupational hazards are strongly associated with human sinonasal SCC, 21,31,32 these tumours might also show a different behaviour than their canine counterparts. Currently, monoclonal antibodies especially against EGFR 69,70 and VEGFR 71 are being investigated in human sinus carcinoma 18–20 …”

Section: Discussionmentioning

confidence: 99%

“…68 Considering that smoking and occupational hazards are strongly associated with human sinonasal SCC, 21,31,32 these tumours might also show a different behaviour than their canine counterparts. Currently, monoclonal antibodies especially against EGFR 69,70 and VEGFR 71 are being investigated in human sinus carcinoma. [18][19][20] There are several limitations to this study: diagnosis was based on clinical findings as well as cytological or histological and diagnostic imaging reports.…”

Section: Discussionmentioning

confidence: 99%

Frontal sinus carcinoma in forty‐one dogs (2001–2022)

Gedon¹,

Kessler²,

Schmidt³

2023

Vet Comparative Oncology

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Reports on canine frontal sinus carcinomas (FSCs) are scarce. This retrospective review of 41 dogs with FSC (2001–2022) describes demographic and clinical characteristics of canine FSC and reports the clinical experience and overall survival following treatment with toceranib phosphate (TOC) and meloxicam in 10 cases. Median age at diagnosis was 10.6 years (range: 6.5–15.4 years). There was a male‐to‐female‐ratio of 2.4:1. The most common breeds were Jack Russell Terriers (JRT) (n = 7; 17.1%) and Rottweilers (n = 3, 7.3%). Mesocephalic breeds (70.6%) were most commonly affected, brachycephalics accounted for 8.8%. The most frequent clinical signs included skull deformation dorsomedial to the eye (87.5%), pain/head‐shyness (40.0%), ocular (22.5%)/nasal (17.5%) discharge, and exophthalmos (17.5%). Duration of symptoms prior to diagnosis varied from a few days to 9 months. There were no neurological signs at initial presentation despite imaging evidence of osteolysis of the lamina interna of the frontal bone in most dogs (69.4%). In 11.5%, pulmonary changes suggestive of metastasis or concurrent primary pulmonary neoplasia were present. Tumour types included squamous cell carcinoma (58.5%), unspecified carcinoma (29.3%), and adenocarcinoma (9.8%). Ten dogs were treated with TOC (median 2.8 mg/kg EOD or three times per week) and meloxicam (0.1 mg/kg, EOD) (TOC‐M), resulting in subjective regression of skull deformity in 8/10 (80.0%) patients. Overall median survival time with TOC‐M was 183.5 days (range: 120–434 days). FSCs typically present with skull deformation, but no overt neurological signs. Male dogs and JRT may be overrepresented. The use of TOC‐M in FSC appears promising and warrants further prospective evaluation.

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“…Other explanations of differences between DN-SCC and IP-SCC include molecular differences that may impact clinical behavior and outcomes. For instance, a recent study reported a higher prevalence of EGFR mutations in IP-SCC that are less frequently observed in DN-SCC (44) . Additionally, a recent study demonstrated progressive upregulation of several genes unique to malignant transformation of IP-SCC that may impact different outcomes compared to DN-SCC (45,46) .…”

Section: O R R E C T E D P R O O Fmentioning

confidence: 99%

Recurrence rates of de-novo versus inverted papilloma-transformed sinonasal squamous cell carcinoma: a meta-analysis

Birkenbeuel¹,

Goshtasbi²,

Adappa³

et al. 2022

Rhin

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Background: There is a paucity of reporting on recurrence patterns of de-novo sinonasal squamous cell carcinoma (DN-SCC) and inverted-papilloma-transformed sinonasal squamous cell carcinoma (IP-SCC). Method: A systematic literature review queried studies comparing recurrence patterns in patients with both DN-SCC and IP-SCC. Primary outcomes included local and regional recurrence and rates of distant metastasis. Of the 595 studies screened, eight were included. Results: Patients with DN-SCC had significantly higher rates of positive margins, advanced T classification (T3/T4), treatment with chemotherapy and radiotherapy. There were no significant differences in local recurrence or regional recurrence. Overall risk of distant metastasis was lower in IP-SCC. DN-SCC, compared to IP-SCC, is more likely to present with advanced TNM classification and have positive margins after surgical resection, which may affect rates of distant metastasis and recurrence. Conclusions: The findings in this study suggest IP-SCC may be a less aggressive malignancy compared to DN-SCC, with the possibility of a reduced role for adjuvant therapy in IP-SCC. Further studies are required to better understand differences in tumor biology and treatments strategies between IP-SCC and DN-SCC.

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EGFR Exon 20 Insertion Mutations in Sinonasal Squamous Cell Carcinoma

Cited by 7 publications

References 107 publications

High 4-1BB Expression in PBMCs and Tumor Infiltrating Lymphocytes (TILs) in Patients with Head and Neck Squamous Cell Carcinoma

High 4-1BB Expression in PBMCs and Tumor Infiltrating Lymphocytes (TILs) in Patients with Head and Neck Squamous Cell Carcinoma

Frontal sinus carcinoma in forty‐one dogs (2001–2022)

Recurrence rates of de-novo versus inverted papilloma-transformed sinonasal squamous cell carcinoma: a meta-analysis

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