EGFR Exon 20 Insertion Mutations in Sinonasal Squamous Cell Carcinoma

Recurrent epidermal growth factor receptor (EGFR)-activating mutations have been identified in a rare form of head and neck cancer known as sinonasal squamous cell carcinoma (SNSCC), a malignant disease with a 5-year mortality rate of ~40%. Interestingly, the majority of EGFR mutations identified in patients with primary SNSCC are exon 20 insertions (Ex20ins), which is in contrast to non-small-cell lung cancer (NSCLC), where the EGFR exon 19 deletion and L858R mutations predominate. These studies demonstrate that EGFR Ex20ins mutations are not exclusive to lung cancer as previously believed, but are also involved in driving SNSCC pathogenesis. Here we review the landscape of EGFR mutations in SNSCC, with a particular focus on SNSCC associated with inverted sinonasal papilloma (ISP), a benign epithelial neoplasm. Taking lessons from NSCLC, we also discuss potential new treatment options for ISP-associated SNSCC harbouring EGFR Ex20ins in the context of targeted therapies, drug resistance and precision cancer medicine. Moving forward, further basic and translational work is needed to delineate the biology of EGFR Ex20ins in SNSCC in order to develop more effective treatments for patients with this rare disease.

Download Full-text

Detection of clinically relevant epidermal growth factor receptor pathway mutations in circulating cell-free tumor DNA using next generation sequencing in squamous cell carcinoma lung

South Asian Journal of Cancer ◽

10.4103/sajc.sajc_281_18 ◽

2019 ◽

Vol 08 (04) ◽

pp. 247-249

Author(s):

Kanakasetty Babu Govind ◽

Deepak Koppaka ◽

Lokanatha Dasappa ◽

Linu Abraham Jacob ◽

Suresh M.C. Babu ◽

...

Keyword(s):

Lung Cancer ◽

Squamous Cell Carcinoma ◽

Epidermal Growth Factor Receptor ◽

Cell Carcinoma ◽

Squamous Cell ◽

Growth Factor Receptor ◽

Braf Mutations ◽

Lung Cancer Patients ◽

Epidermal Growth ◽

Generation Sequencing

Abstract Background: Limited repertoires of targets are available in the management of squamous cell carcinoma lung. In this study, we analyzed epidermal growth factor receptor (EGFR), RAS, BRAF mutations in lung cancer patients of squamous cell histology using next-generation sequencing (NGS) on the circulating cell-free DNA (cf-DNA). Materials and Methods: In this prospective observational study, patients with squamous cell carcinoma lung, either newly diagnosed or having a progressive disease on prior therapy were eligible. Cf-DNA was extracted from peripheral blood and analyzed for EGFR, KRAS, NRAS, and BRAF mutations using NGS. Results: Sixteen patients were enrolled over a period of 1 month. The mean cf-DNA quantity extracted from the plasma was 96.5 ng (range, 15–200 ng). Eight clinically relevant mutations in the EGFR pathway were identified. These include Exon 21 mutations in 4 patients, Exon 20 mutation in onepatient, complex mutations with coexisting Exon 21 and Exon18 in one patient and KRAS Exon 2 mutations in two patients. Conclusion: cf-DNA is a minimally invasive technique for detection of clinically relevant mutations in lung cancer patients. The use of novel advanced techniques such as NGS may help in detecting EGFR pathway mutations in patients with squamous cell carcinoma lung.

Download Full-text

Incidence and the clinical outcomes of epidermal growth factor receptor (EGFR) mutations in male smokers with squamous cell carcinoma of lung

European Journal of Cancer Supplements ◽

10.1016/s1359-6349(08)71599-4 ◽

2008 ◽

Vol 6 (9) ◽

pp. 111-112

Author(s):

S. Park ◽

E. Cho ◽

D. Shin

Keyword(s):

Squamous Cell Carcinoma ◽

Epidermal Growth Factor Receptor ◽

Growth Factor ◽

Epidermal Growth Factor ◽

Cell Carcinoma ◽

Clinical Outcomes ◽

Squamous Cell ◽

Growth Factor Receptor ◽

Egfr Mutations ◽

Epidermal Growth

Download Full-text

Squamous Cell Carcinoma of the Lung with Metastasis to the GI Tract Associated with EGFR Exon 19 Deletion

Case Reports in Medicine ◽

10.1155/2013/874836 ◽

2013 ◽

Vol 2013 ◽

pp. 1-2 ◽

Cited By ~ 2

Author(s):

Glen J. Weiss ◽

Agnes K. Liman ◽

Jeffrey Allen ◽

Philip Y. Cheung ◽

Rajesh N. Kukunoor

Keyword(s):

Squamous Cell Carcinoma ◽

Epidermal Growth Factor Receptor ◽

Cell Carcinoma ◽

Squamous Cell ◽

Symptom Relief ◽

Growth Factor Receptor ◽

Gi Tract ◽

Exon 19 Deletion ◽

Epidermal Growth ◽

Exon 19

We describe three confirmed cases of squamous cell carcinoma (SCC) of the lung with metastasis to the gastrointestinal (GI) tract, with two having epidermal growth factor receptor (EGFR) exon 19 deletions in all available specimens. One of these patients received EGFR tyrosine kinase directed therapy for a brief period with some symptom relief. Consideration of EGFR exon 19 mutation testing in SCC of the lung, particularly for those with GI tract metastasis, may identify this potentially drug-targetable entity.

Download Full-text

Molecular profiling and characteristics of non-small-cell lung cancer patients in Georgia

Future Oncology ◽

10.2217/fon-2021-0177 ◽

2021 ◽

Author(s):

Ivane Kiladze ◽

Elene Mariamidze ◽

Anna Baramidze ◽

Mariam Lomidze ◽

Ketevan Meladze ◽

...

Keyword(s):

Lung Cancer ◽

Squamous Cell Carcinoma ◽

Small Cell Lung Cancer ◽

Cell Carcinoma ◽

Squamous Cell ◽

Smoking Status ◽

Small Cell ◽

Egfr Mutations ◽

Small Cell Lung ◽

Never Smokers

Aims: In patients with advanced non-small-cell lung cancer, the correlation between histopathology, smoking status, driver oncogene mutations and PD-L1 overexpression were investigated. Patients and methods: A total of 202 patients were identified. Research was done in Georgia. Results: EGFR mutations were detected in 6% of the tested cases (12/187) and five out of 12 EGFR+ cases had histology consistent with squamous cell carcinoma. No statistically significant correlation was observed between PD-L1 expression, smoking status and clinicopathological characteristics. However, the correlation between smoking status and histology was statistically significant (p = 0.0264), as never-smokers had a higher incidence of adenocarcinoma histology. Conclusion: The study showed a small percentage of EGFR mutations associated with adenocarcinoma histology and revealed a solid existence of this mutation in squamous cell carcinoma histology. A higher incidence of adenocarcinoma histology was observed in never-smokers.

Download Full-text

Novel gene signatures for stage classification of the squamous cell carcinoma of the lung

Scientific Reports ◽

10.1038/s41598-021-83668-1 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Angel Juarez-Flores ◽

Gabriel S. Zamudio ◽

Marco V. José

Keyword(s):

Lung Cancer ◽

Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Squamous Cell ◽

Treatment Options ◽

Machine Learning Algorithms ◽

Treatment Development ◽

Cancer Pathology ◽

Novel Concept

AbstractThe squamous cell carcinoma of the lung (SCLC) is one of the most common types of lung cancer. As GLOBOCAN reported in 2018, lung cancer was the first cause of death and new cases by cancer worldwide. Typically, diagnosis is made in the later stages of the disease with few treatment options available. The goal of this work was to find some key components underlying each stage of the disease, to help in the classification of tumor samples, and to increase the available options for experimental assays and molecular targets that could be used in treatment development. We employed two approaches. The first was based in the classic method of differential gene expression analysis, network analysis, and a novel concept known as network gatekeepers. The second approach was using machine learning algorithms. From our combined approach, we identified two sets of genes that could function as a signature to identify each stage of the cancer pathology. We also arrived at a network of 55 nodes, which according to their biological functions, they can be regarded as drivers in this cancer. Although biological experiments are necessary for their validation, we proposed that all these genes could be used for cancer development treatments.

Download Full-text

Squamous cell carcinoma of the scrotum in HIV: two case reports

African Journal of Urology ◽

10.1186/s12301-021-00177-3 ◽

2021 ◽

Vol 27 (1) ◽

Author(s):

Jeff John ◽

Ken Kesner ◽

John Lazarus

Keyword(s):

Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Squamous Cell ◽

Case Reports ◽

Treatment Options ◽

Punch Biopsy ◽

Delayed Treatment ◽

Clinical Presentations ◽

T1 N0 M0

Abstract Background Squamous cell carcinoma (SCC) of the scrotum was the first malignancy known to be associated with exposure to an occupational carcinogen—in this case, soot trapped in the breeches of chimney sweeps. Better civil rules and regulations and the replacement of hearths with other forms of heating have rendered SCC of the scrotum a rarity. We report two cases of scrotal SCC with vastly differing clinical presentations and management. Case presentation Case 1 had T1 N0 M0 disease and presented with a small (< 2 cm), innocuous-looking, non-healing ulcer of eight years duration. A punch biopsy revealed a superficially invasive SCC confirmed on immunohistochemical profiling. A wide local excision of the lesion was subsequently performed. Follow-up at three years showed no signs of recurrence. Case 2 presented with T4 N1 M1 disease and rapidly progressing locally destructive mass. A punch biopsy of the scrotal lesion confirmed invasive moderately differentiated focally keratinising SCC. The metastatic evaluation confirmed the presence of metastatic, extensive para-aortic lymphadenopathy. He was managed with cisplatin-based chemoradiotherapy. Conclusion Early detection and management of patients with SCC of the scrotum are essential. If the diagnosis is delayed, treatment options become limited, and the prognosis is poor. Notwithstanding the rarity of this disease, multicentre trials are needed to provide more precise guidelines as to the optimal management of these patients.

Download Full-text

Re-use of erlotinib in a patient using osimertinib after erlotinib, case report

Journal of Oncology Pharmacy Practice ◽

10.1177/10781552211019108 ◽

2021 ◽

pp. 107815522110191

Author(s):

Pinar Gursoy

Keyword(s):

Lung Cancer ◽

Case Report ◽

Treatment Options ◽

Resistance Mutation ◽

Growth Factor Receptor ◽

Complete Response ◽

Egfr Mutations ◽

T790m Mutation ◽

Development Of Resistance ◽

Exon 19

Introduction Most patients with non-small-cell lung cancer tumors that have epidermal growth factor receptor (EGFR) mutations have deletion mutations in exon 19 or exon 21, or both.In recent years, targeted therapies in lung cancer have increased survival, but the development of resistance to these drugs poses a major problem. Thesubstitution of methionineforthreonine at position 790 (T790M) mutation,is primarily responsible for this resistance. However, after osimertinib used in T790M positivepatients treatment options are generally limited to chemotherapy. Case report We reported the efficacy of erlotinib, which we reapplied due to the disappearance of the resistance mutation after osimertinib in a 68-year-old patient using osimertinib after erlotinib. Management and outcome: In the patient using erlotinib due to exon 19 deletion when progression was observed and T790M positivity was detected, osimertinib treatment was initiated. However, when T790M was found to be negative with rebiopsy in progression after osimertinib, a complete response was achieved by restarting erlotinib. Discussion The strategy of restarting erlotinib treatment with negative T790M mutation detected in biopsies of patients with osimertinib resistance may be an acceptable treatment option.

Download Full-text

Chemotherapy alone versus definitive concurrent chemoradiotherapy for cT4b esophageal squamous cell carcinoma: a population-based study

BMC Gastroenterology ◽

10.1186/s12876-021-01742-4 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Chia-Chin Li ◽

Chih-Yi Chen ◽

Ying-Hsiang Chou ◽

Chih-Jen Huang ◽

Hsiu-Ying Ku ◽

...

Keyword(s):

Squamous Cell Carcinoma ◽

Esophageal Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Squamous Cell ◽

Concurrent Chemoradiotherapy ◽

Statistical Significance ◽

Treatment Options ◽

Population Based ◽

Primary Analysis

Abstract Background The role of radiotherapy for cT4bNanyM0 esophageal squamous cell carcinoma (ESqCC) is relatively unclear, with both chemotherapy (C/T) alone and definitive concurrent chemoradiotherapy (dCCRT) being treatment options in the current guidelines. We aimed to compare the survival of dCCRT versus C/T for these patients via a population-based approach. Methods Eligible cT4b ESqCC patients diagnosed between 2011 and 2017 were identified via the Taiwan Cancer Registry. We used propensity score (PS) weighting to balance the observable potential confounders between groups. The hazard ratio (HR) of death and incidence of esophageal cancer mortality (IECM) were compared between dCCRT and C/T. We also evaluated OS in subgroups of either low or standard radiotherapy doses. Results Our primary analysis consisted of 247 patients in whom covariates were well balanced after PS weighing. The HR for death when dCCRT was compared with C/T was 0.36 (95% confidence interval 0.24–0.53, P < 0.001). Similar results were found for IECM. Statistical significance was only observed in the standard RT dose but not in the low dose in subgroup analyses. Conclusions In this population-based nonrandomized study of cT4bNanyM0 ESqCC patients from Asia (Taiwan), we found that the use of radiotherapy with chemotherapy was associated with better overall survival than chemotherapy alone. Further studies (especially RCTs) are needed to confirm our findings.

Download Full-text