Clinically significant sub-clonality for common drivers can be detected in 26% of <i>KRAS/EGFR</i> mutated lung adenocarcinomas

Simon, Einav; Bick, Tova; Sarji, Shada; Shentzer, Talia; Prinz, Elad; Yehiam, Liza; Sabo, Edmond; Ben‐Izhak, Ofer; Hershkovitz, Dov

doi:10.18632/oncotarget.17399

Cited by 5 publications

(2 citation statements)

References 48 publications

(74 reference statements)

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“…Compared with other patterns, IMA showed a higher frequency of KRAS mutation (3 of 7 cases; 42.9%). These trends in gene mutational patterns have been reported in previous studies 31–36 …”

Section: Discussionsupporting

confidence: 85%

“…These trends in gene mutational patterns have been reported in previous studies. [31][32][33][34][35][36] The sub-classification of ADC has been reported to have significant prognostic predictive factors since the IASLC/ATS/ERS classification was published. [4][5][6] Rodriguez et al 10,11 attempted to distinguish the ADC subtypes using cytological specimens, and the authors noted that architectural and nuclear features may be helpful, particularly in distinguishing the solid pattern from the other predominant patterns.…”

Section: Discussionmentioning

confidence: 99%

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Cytomorphometric and flow cytometric analyses using liquid‐based cytology materials in subtypes of lung adenocarcinoma

Tanaka

Fujiwara

Sakamoto

et al. 2022

Diagnostic Cytopathology

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Background The histological classifications of invasive lung adenocarcinoma subtypes are considered to predict patient prognosis after surgical treatment. The objectives of this study were to evaluate cytomorphological characteristics and proliferative activities among the histological predominant patterns by performing cytomorphometric and flow cytometric analyses using liquid‐based cytology materials. Methods Cytological samples fixed by liquid‐based cytology preservatives from 53 surgically‐resected lung adenocarcinoma specimens were obtained between August 2018 and November 2019. The Papanicolaou‐stained and paired Ki‐67‐stained slides were analyzed for calculating nuclear morphology (nuclear area, nuclear perimeter and nuclear circularity) and Ki‐67 labeling index using software. The cell proliferation index (CPIx) was calculated and cellular information including cell cycle stage of tumor cells was obtained by flow cytometry. Results The 53 cases included papillary (n = 29), acinar (n = 8), lepidic (n = 5), and solid (n = 4) subtypes, and invasive mucinous adenocarcinoma (n = 7) were also included. In the lepidic pattern, nuclear area (79.6 ± 28.8 μm2) and perimeter (34.1 ± 6.1 μm) were relatively larger and longer than those of the other predominant patterns. The Ki‐67 labeling index of the solid pattern (27.9 ± 12.5%) was highest compared with those of other predominant patterns. There were statistically significant differences in the lepidic versus solid patterns and the papillary versus solid patterns (p = .013 and p = .039, respectively). The calculated mean CPIx of the lepidic and the acinar patterns were approximately two‐fold higher than those of the other predominant patterns. Conclusion By revealing the differences of cytomorphological characteristics, these methodologies might be used for diagnosing cytopathological materials using digital cytopathology.

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Section: Discussionsupporting

confidence: 85%

Section: Discussionmentioning

confidence: 99%

Cytomorphometric and flow cytometric analyses using liquid‐based cytology materials in subtypes of lung adenocarcinoma

Tanaka

Fujiwara

Sakamoto

et al. 2022

Diagnostic Cytopathology

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Efficacy of EGFR tyrosine kinase inhibitors in non-small cell lung cancer patients harboring different types of EGFR mutations: A retrospective analysis

et al. 2017

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With the development of molecular pathology, many types of epidermal growth factor receptor (EGFR) mutations have been identified. The efficacy of EGFR tyrosine kinase inhibitors (EGFR-TKIs) in non-small cell lung cancer (NSCLC) patients with different types of EGFR mutations, especially in patients with single rare mutations or complex mutations (co-occurrence of two or more different mutations), has not been fully understood. This study aimed to examine the efficacy of EGFR-TKIs in NSCLC patients with different types of EGFR mutations. Clinical data of 809 NSCLC patients who harbored different types of EGFR mutations and treated from January 2012 to October 2016 at Renmin Hospital and Zhongnan Hospital, Wuhan, were retrospectively reviewed. The clinical characteristics of these patients and the efficacy of EGFR-TKIs were analyzed. Among these patients, 377 patients had only the EGFR del-19 mutation, 362 patients the EGFR L858R mutation in exon 21, 33 patients single rare mutations and 37 patients complex mutations. Among these 809 patients, 239 patients were treated with EGFR-TKIs. In all the 239 patients, the disease control rate (DCR) was 93.7% with two patients (0.2%) achieving complete response (CR), the median progression free survival (PFS) was 13.0 months (95% confidence interval [CI], 11.6-14.4 months), and the median overall survival (OS) was 55.0 months (95% CI, 26.3-83.7 months). Subgroup analysis revealed that the DCR in patients harboring single rare or complex mutations of EGFR was significantly lower than in those with del-19 or L858R mutation (P<0.001). Patients with classic mutations (del-19 and/or L858R mutations) demonstrated longer PFS (P<0.001) and OS (P=0.017) than those with uncommon mutations (single rare and/or complex mutations). Furthermore, the patients with single rare mutations had shorter median OS than in those with other mutations. Multivariate Cox regression analysis identified that the type of EGFR mutations was an independent risk factor for PFS (hazard ratio [HR]=0.308, 95% CI, 0.191-0.494, P<0.001) and OS (HR=0.221, 95% CI, 0.101-0.480, P<0.001). The results suggest that the single rare or complex EGFR mutations confer inferior efficacy of EGFR-TKIs treatment to the classic mutations. The prognosis of the single rare EGFR mutations is depressing. EGFR-TKIs may be not a good choice for NSCLC patients with single rare mutations of EGFR. Further studies in these patients with uncommon mutations (especially for the patients with single rare mutations) are needed to determine a better precision treatment.

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Comparison of the somatic genomic landscape between central- and peripheral-type non-small cell lung cancer

Wang,

Diao,

Zhang

et al. 2024

Lung Cancer

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Clinically significant sub-clonality for common drivers can be detected in 26% of KRAS/EGFR mutated lung adenocarcinomas

Cited by 5 publications

References 48 publications

Cytomorphometric and flow cytometric analyses using liquid‐based cytology materials in subtypes of lung adenocarcinoma

Cytomorphometric and flow cytometric analyses using liquid‐based cytology materials in subtypes of lung adenocarcinoma

Efficacy of EGFR tyrosine kinase inhibitors in non-small cell lung cancer patients harboring different types of EGFR mutations: A retrospective analysis

Comparison of the somatic genomic landscape between central- and peripheral-type non-small cell lung cancer

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