Dataset Information

Different spatial distributions of brain metastases from lung cancer by histological subtype and mutation status of epidermal growth factor receptor.

ABSTRACT:

Background

The purpose of this study was to test the hypothesis that the genetic backgrounds of lung cancers could affect the spatial distribution of brain metastases.

Methods

CT or MR images of 200 patients with a total of 1033 treatment-naive brain metastases from lung cancer were retrospectively reviewed (23 by CT and 177 by MRI). All images were standardized to the human brain MRI atlas provided by the Montreal Neurological Institute 152 database. Locations, depths from the brain surface, and sizes of the lesions after image standardization were analyzed.

Results

The posterior fossa, the anatomic "watershed areas," and the gray-white matter junction were confirmed to be more commonly affected by lung cancer brain metastases, and brain metastases with epidermal growth factor receptor (EGFR) L858R mutation occurred more often in the caudate, cerebellum, and temporal lobe than those with exon 19 deletion of EGFR. Median depths of the lesions from the brain surface were 13.7 mm (range, 8.6-21.9) for exon 19 deleted EGFR, 11.5 mm (6.6-16.8) for L858R mutated, and 15.0 mm (10.0-20.7) for wild-type EGFR. Lesions with L858R mutated EGFR were located significantly closer to the brain surface than lesions with exon 19 deleted or wild-type EGFR (P = .0032 and P < .0001, respectively). Furthermore, brain metastases of adenocarcinoma lung cancer patients with a history of chemotherapy but not molecular targeted therapy were located significantly deeper from the brain surface (P = .0002).

Conclusion

This analysis is the first to reveal the relationship between EGFR mutation status and the spatial distribution of brain metastases of lung cancer.

SUBMITTER: Takano K

PROVIDER: S-EPMC4827044 | biostudies-literature | 2016 May

REPOSITORIES: biostudies-literature

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Publications

Different spatial distributions of brain metastases from lung cancer by histological subtype and mutation status of epidermal growth factor receptor.

Takano Koji K Kinoshita Manabu M Takagaki Masatoshi M Sakai Mio M Tateishi Souichirou S Achiha Takamune T Hirayama Ryuichi R Nishino Kazumi K Uchida Junji J Kumagai Toru T Okami Jiro J Kawaguchi Atsushi A Hashimoto Naoya N Nakanishi Katsuyuki K Imamura Fumio F Higashiyama Masahiko M Yoshimine Toshiki T

Neuro-oncology 20151031 5

<h4>Background</h4>The purpose of this study was to test the hypothesis that the genetic backgrounds of lung cancers could affect the spatial distribution of brain metastases.<h4>Methods</h4>CT or MR images of 200 patients with a total of 1033 treatment-naive brain metastases from lung cancer were retrospectively reviewed (23 by CT and 177 by MRI). All images were standardized to the human brain MRI atlas provided by the Montreal Neurological Institute 152 database. Locations, depths from the br ...[more]

PMID: 26519739

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Project description:BackgroundPrevious studies have reported differential associations of certain dietary factors such as soy consumption by epidermal growth factor receptor mutant (EGFR +) subtype of non-small cell lung cancer (NSCLC). However, whether the other dietary factors including meat, fruits, and vegetables have differential risks on different histological and molecular subtypes of lung cancer remains unclear. Therefore, we conducted a case-control study to evaluate these associations.MethodsA total of 3,170 cases and 4,238 controls from three different studies (Genes and Environment in Lung Cancer Study, Lung Cancer Consortium Singapore Study, and Multi-ethnic Cohort Study) were included. Information on demographics, lifestyle, and dietary consumption was obtained using questionnaires. Diet was assessed by using the number of standard servings of each item consumed per week. Multivariable logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the association between meat, vegetables, and fruits consumption with lung cancer risk after adjusting for potential confounders.ResultsWe identified a significant inverse association between higher consumption of fruits and the risk of lung cancer (2nd tertile: OR = 0.54, 95%CI = 0.46-0.65; 3rd tertile: OR = 0.77, 95%CI = 0.65-0.91), compared with the lower (1st tertile) consumption of fruits. Higher vegetable consumption was significantly associated with a lower risk of EGFR + lung cancer (OR = 0.69, 95% CI = 0.54-0.88), however, this association was not significant among EGFR wild-type (-) lung cancer. Conversely, higher consumption of total meat (OR = 2.10, 95%CI = 1.58-2.79) was significantly associated with higher lung cancer risk, as compared with the lower consumption group.ConclusionsDifferential associations between vegetable consumption with EGFR mutation status in NSCLC were found. Further prospective studies are warranted to assess this association and elucidate the biological mechanisms.

Project description:The present study aimed to investigate the association between epidermal growth factor receptor (EGFR)/Kirsten rat sarcoma viral oncogene homolog (KRAS) mutations, anaplastic lymphoma receptor tyrosine kinase (ALK) rearrangements and the morphological characteristics of lung adenocarcinoma (LAC), according to the International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society (IASLC/ATS/ERS) classification in a large group of patients with primary LAC. A total of 200 patients with invasive LAC who had undergone complete resections at the Beijing Chest Hospital (Beijing, China) were randomly selected. The morphology of the samples was reassessed in 5% increments by two pathologists, according to the IASLC/ATS/ERS scheme. EGFR and KRAS mutations were tested by direct DNA sequencing. ALK rearrangements were screened by immunohistochemistry on a Benchmark XT stainer. The data revealed that EGFR and KRAS mutations, and ALK rearrangements were identified in 46.0% (92/200), 9.0% (18/200) and 11.5% (23/200) of the patients, respectively. The EGFR/KRAS mutations and ALK rearrangements were mostly exclusive. However, 1 patient exhibited the coexistence of the EGFR (at exon 20) and KRAS (codon 12) mutations, and another patient exhibited the coexistence of the EGFR mutation (at exon 21) and the ALK gene fusion. EGFR mutations were indicated to be closely associated with the acinar predominant (43/77; 55.8%; P=0.030) and papillary predominant (26/49; 53.1%; P=0.006) subtypes. KRAS mutations were more commonly associated with the solid predominant subtype (9/52; 17.3%; P=0.023) and invasive mucinous LAC (5/10; 50.0%; P=0.004), and less commonly associated with the acinar predominant subtype (1/77; 1.3%; P=0.002). ALK rearrangements more commonly occurred in the solid predominant subtype compared with other subtypes (13/52; 25%; P=0.002), and less commonly occurred in the papillary predominant subtype (1/49; 2.0%; P=0.004). Tumors harboring ALK rearrangements were characterized by signet-ring cell (7/9; 77.8%; P<0.0001) and cribriform (7/12; 58.3%; P<0.0001) patterns. The association between the mutation status and histological subtype in LAC was distinct. The predominant subtype according to the IASLC/ATS/ERS classification provided important information for gene mutations and integrated clinical findings to improve the treatment of LAC patients.

Dataset Information

Different spatial distributions of brain metastases from lung cancer by histological subtype and mutation status of epidermal growth factor receptor.

Background

Methods

Results

Conclusion

Publications

Different spatial distributions of brain metastases from lung cancer by histological subtype and mutation status of epidermal growth factor receptor.

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