Abnormalities of epidermal growth factor receptor in lung squamous‐cell carcinomas, adenosquamous carcinomas, and large‐cell carcinomas

Ohtsuka, Kouki; Ohnìshì, H.; Fujiwara, Masachika; Kishino, Tomonori; Matsushima, Satsuki; Furuyashiki, Go; Takei, Hidefumi; Koshiishi, Yoshihiko; Goya, Tomoyuki; Watanabe, Takashi

doi:10.1002/cncr.22476

Cited by 68 publications

(48 citation statements)

References 41 publications

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“…All patients bearing a EGFRvIII mutation were male, smokers, and seven had squamous cell carcinoma, whereas one had poorly differentiated adenocarcinoma. However, in the investigation of Ohtsuka et al, 99 EGFRvIII mutation was detected in one of seven squamous cell carcinomas with an adenocarcinoma component, in two of four adenosquamous carcinomas and in one of seven large cell carcinomas.…”

Section: Egfrviii Mutationmentioning

confidence: 89%

“…The information concerning whether EGFRvIII mutation is associated with specific histological types of lung cancer is conflicting, although most studies have indicated that EGFRvIII is associated with squamous cell carcinoma. 98,99 In the study by Sasaki et al, 97 EGFRvIII mutation was detected in 3% (8/ 252) of non-selected lung cancer patients. All patients bearing a EGFRvIII mutation were male, smokers, and seven had squamous cell carcinoma, whereas one had poorly differentiated adenocarcinoma.…”

Section: Egfrviii Mutationmentioning

confidence: 98%

“…27,41,99 However, EGFR mutations in squamous cell carcinoma appear to occur much less frequently, with a reported incidence as high as 14% from a group of seven patients to as low as 0% in a group of 454 squamous cell lung cancers. 27,41,99 The National Comprehensive Cancer Network recommends erlotinib as the first-line therapy for patients who have an EGFR mutation and who have advanced, recurrent, or metastatic adenocarcinoma. 3 Adenosquamous carcinomas appear to have an EGFR mutation incidence that is similar to that of adenocarcinomas.…”

Section: Other Alterations That Affect the Egfr Tki Responsementioning

confidence: 99%

“…EGFRvIII mutations were found in 5% of human lung squamous cell carcinomas (also see prior discussion) (Figure 4). 98,99 The advent of targeted therapy based on driver mutations in lung adenocarcinoma has countered the notion that non-small cell lung cancer (NSCLC) is a distinct clinical entity. Current information indicates that distinguishing a tumor as NSCLC alone is no longer sufficient for patient management and the term 'non-small cell lung cancer (NSCLC)' should be abandoned.…”

Section: Other Alterations That Affect the Egfr Tki Responsementioning

confidence: 99%

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Molecular pathology of lung cancer: key to personalized medicine

et al. 2012

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The majority of lung adenocarcinoma patients with epidermal growth factor receptor-(EGFR) mutated or EML4-ALK rearrangement-positive tumors are sensitive to tyrosine kinase inhibitors. Both primary and acquired resistance in a significant number of those patients to these therapies remains a major clinical problem. The specific molecular mechanisms associated with tyrosine kinase inhibitor resistance are not fully understood. Clinicopathological observations suggest that molecular alterations involving so-called 'driver mutations' could be used as markers that aid in the selection of patients most likely to benefit from targeted therapies. In this review, we summarize recent developments involving the specific molecular mechanisms and markers that have been associated with primary and acquired resistance to EGFR-targeted therapy in lung adenocarcinomas. Understanding these mechanisms may provide new treatment avenues and improve current treatment algorithms.

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Section: Egfrviii Mutationmentioning

confidence: 89%

Section: Egfrviii Mutationmentioning

confidence: 98%

Section: Other Alterations That Affect the Egfr Tki Responsementioning

confidence: 99%

Section: Other Alterations That Affect the Egfr Tki Responsementioning

confidence: 99%

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Molecular pathology of lung cancer: key to personalized medicine

et al. 2012

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“…Activating mutations in this receptor tyrosine kinase cause constitutive activation of the mitogen-activated protein kinase pathway, driving increased cellular motility, invasiveness, and resistance to apoptosis. Activating EGFR mutations are known to underlie a significant number of adenocarcinomas 4 , but can also be the drivers behind a smaller number of adenosquamous 5 or squamous cell carcinomas harbouring adenocarcinomatous components 6 . Established clinical risk factors for an egfr-driven lung cancer include female sex and absence of a heavy tobacco-smoking history 7 .…”

Section: Introductionmentioning

confidence: 99%

Relationship of Thyroid Transcription Factor 1 to EGFR Status in Non-Small-Cell Lung Cancer

et al. 2014

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Background: Activating mutations of the epidermal growth factor receptor (EGFR) gene are known to drive a proportion of non-small-cell lung cancers. Identification of lung cancers harbouring such mutations can lead to effective treatment using one of the agents that targets and blocks EGFR-mediated signalling. Methods: All specimens received at the BC Cancer Agency (Vancouver) for EGFR testing were prospectively identified and catalogued, together with clinical information and EGFR status, over a 14-month period. Results: Specimens from 586 patients were received for EGFR testing, and EGFR status was reported for 509 patients. No relationship between specimen type or site of origin and EGFR test failure rate was identified. Concurrent immunohistochemical (IHC) status for thyroid transcription factor 1 (TTF1) was available for 309 patients. The negative predictive value of TTF1-negative status by IHC was 94.2% for predicting negative EGFR status. Conclusions: In patients with limited tissue available for testing, a surrogate for EGFR status would aid in timely management. Immunohistochemistry for TTF1 is readily available and correlates highly with EGFR status. In conjunction with genetic assays, TTF1 could be used to optimize an EGFR testing strategy.

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Efficacy of icotinib in advanced lung squamous cell carcinoma

Liang

Tan

et al. 2018

Cancer Medicine

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BackgroundThere are controversial data supporting the efficacy of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) in patients with advanced lung squamous cell carcinoma (SCC). In this study, the efficacy of icotinib in unselected and EGFR‐mutated patients with lung SCC was assessed.MethodsWe retrospectively analyzed the survival time of unselected advanced lung SCC patients treated with icotinib for at least 5 months between June 2013 and June 2016, and selected appropriate EGFR‐mutated advanced lung ADC patients to have 1:1 ratio of propensity score matching with EGFR‐mutated advanced lung SCC patients, and matching factors were age, sex, clinical stage, Karnofsky performance status (KPS), smoking history, EGFR mutation type, and treatment lines.ResultsA total of 487 unselected advanced lung SCC patients were available for analysis of icotinib treatment efficacy. The progression‐free survival (PFS) was 13.0 months (95% CI 12.2‐13.8), the overall survival (OS) was 16.0 months (95% CI 14.7‐17.3), and the objective response rate (ORR) was 41.3%. After propensity score matching, 78 EGFR‐mutated lung SCC and 78 EGFR‐mutated lung ADC patients were selected and compared. Although no statistical difference was found, ADC patients were associated with a longer PFS (15.8 months vs 12.7 months, P = 0.275) and OS (24.2 months vs 18.5 months, P = 0.150), and a better ORR (59.0% vs 48.7%, P = 0.199) than compared with SCC patients when treated with icotinib.ConclusionIcotinib has a modest therapeutic effect in patients with advanced lung SCC, especially for the population with EGFR mutations.

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Abnormalities of epidermal growth factor receptor in lung squamous‐cell carcinomas, adenosquamous carcinomas, and large‐cell carcinomas

Cited by 68 publications

References 41 publications

Molecular pathology of lung cancer: key to personalized medicine

Molecular pathology of lung cancer: key to personalized medicine

Relationship of Thyroid Transcription Factor 1 to EGFR Status in Non-Small-Cell Lung Cancer

Efficacy of icotinib in advanced lung squamous cell carcinoma

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