Anaplastic lymphoma kinase gene rearrangement in non-small-cell lung cancer in a Brazilian population

Lopes, Lisandro F.; Bacchi, Carlos E.

doi:10.6061/clinics/2012(07)23

Cited by 17 publications

(10 citation statements)

References 42 publications

(30 reference statements)

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“…There were no differences between the ALK rearrangement incidence and smoking status, disease stage, lymph node metastases, histologic subtypes, and survival. Previous studies have reported that the frequency of the ALK rearrangements in NSCLCs using FISH ranged from 3 to 13% [34,35,36,37,38]. Values of 3-11% ALK positivity were found for the Chinese population in several studies [22,39,40,41,42], with the inconsistency reported resulting from factors including the methodology used to detect the ALK rearrangements and the patients enrolled in the studies.…”

Section: Discussionmentioning

confidence: 97%

Mutational Profile and New IASLC/ATS/ERS Classification Provide Additional Prognostic Information about Lung Adenocarcinoma: A Study of 125 Patients from Brazil

Melo

Sá²,

Sternberg

et al. 2015

Oncology

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Aim: To show additional prognostic information about the mutational profile and new International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society (IASLC/ATS/ERS) classification of adenocarcinoma (ADC) in patients without epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor treatments. Methods: In human lung ADC patients (n = 125), including 24 lepidic, 67 acinar, 23 papillary, and 11 solid predominant subtypes, EGFR and KRAS were sequenced, and anaplastic lymphoma kinase (ALK) rearrangements were screened using fluorescence in situ hybridization (FISH). Results:EGFR was mutated in 21.6% of patients with 19.57% showing a mean expression. The most frequent EGFR mutation was a deletion in exon 19, followed by an L858R amino acid substitution in exon 21. KRAS was mutated in 26.4% of patients with 50% displaying mean expression. ALK rearrangement was detected in 6 patients (4.8%). Predominant acinar ADC was strongly associated with EGFR and KRAS mutation. Clinical stage, lymph node metastases, and EGFR mutation in exon 18 showed a significant difference in disease-free and overall survival, but only a trend significance for EGFR and KRAS mutations. Multivariate analysis revealed that men aged >71 years, with a history of smoking (<72 packs/year), clinical stage I/II, and acinar histologic subtype presented better survival than women aged ≤71 years, with a history of smoking (>72 packs/year), and having a predominant solid ADC and EGFR mutation in exon 18. Conclusions: These results indicate that the mutational profile and new IASLC/ATS/ERS classification provide additional prognostic information about lung ADC.

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Section: Discussionmentioning

confidence: 97%

Mutational Profile and New IASLC/ATS/ERS Classification Provide Additional Prognostic Information about Lung Adenocarcinoma: A Study of 125 Patients from Brazil

Melo

Sá²,

Sternberg

et al. 2015

Oncology

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“…Local studies in some Latin American countries have previously reported the frequency of this rearrangement in NSCLC (Brazil 3.2%, Argentina 4.2%, and Mexico 9.0%) [23-25]. Reliable information regarding ALKr frequencies and disparities among ethnic groups is critical.…”

Section: Introductionmentioning

confidence: 99%

Molecular Epidemiology of <b><i>ALK</i></b> Rearrangements in Advanced Lung Adenocarcinoma in Latin America

Arrieta

Cardona²,

Bramuglia

et al. 2018

Oncology

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Objective: Latin American countries are heterogeneous in terms of lung cancer incidence and exposure to potential carcinogens. We evaluated the frequency and clinical characteristics of ALK rearrangements (ALKr) in Latin America. Methods: A total of 5,130 lung cancer patients from 10 Latin American countries were screened for inclusion. ALKr detection was performed by fluorescence in situ hybridization (FISH), immunohistochemistry (IHC), and real-time reverse transcriptase-polymerase chain reaction (RT-PCR) to assess method variability. Demographic and clinicopathologic characteristics were analyzed. Results: Among the 5,130 patients screened, 8.4% (n = 433) had nonevaluable FISH tests. Evaluable FISH analyses revealed positive ALKr in 6.8% (320/4,697) of the study population, which included patients from 9 countries. ALKr distribution for each country was: Mexico 7.6% (79/1,034), Colombia 4.1% (10/242), Argentina 6.0% (153/2,534), Costa Rica 9.5% (13/137), Panama 4.4% (5/114), Uruguay 5.4% (2/37), Chile 8.6% (16/185), Venezuela 8.9% (13/146), and Peru 10.8% (29/268). RT-PCR showed high positive (83.6%) and negative (99.7%) predictive values when compared to the gold standard FISH. In contrast, IHC only showed a high negative predictive value (94.6%). Conclusions: Although there is a clear country and continental variability in terms of ALKr frequency, this difference is not significant and the overall incidence of ALKr in Latin America does not differ from the rest of the world.

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“…We greatly enjoyed reading the thought-provoking article by Lopes et al in a recent issue of your esteemed journal (1). Interestingly, in recent years, data have emerged regarding a role for EML4 (echinoderm microtubule-associated protein-like 4)–ALK (anaplastic lymphoma kinase) in personalized treatment for advanced non-small-cell lung cancer (NSCLC) (2,3).…”

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confidence: 99%

“…EML4-ALK fusion, EGFR , and KRAS mutations are all mutually exclusive, implicating ALK rearrangement as a potential therapeutic target in EGFR wild-type and KRAS wild-type lung cancers (5). Nevertheless, Lopes' study (1) raises some interesting questions. Was patient selection for the study carried out appropriately?…”

mentioning

confidence: 99%

“…Thus, the refined understanding of the NSCLC molecular profile described over the last decade has proven to be an important tool to help medical oncologists develop new approaches for NSCLC treatment. Despite the small frequency of advanced NSCLC patients who present with EML4-ALK fusion (2.4 to 6.7%) (1), we believe that all patients in this setting should have the opportunity to receive such innovative therapies and approaches. However, further studies are warranted to establish the appropriate pharmaco-economic profiles.…”

mentioning

confidence: 99%

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Anaplastic lymphoma kinase gene rearrangement and non-small cell lung cancer management: a step forward in personalized therapy

Mello¹,

Araújo²

2013

Clinics

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Anaplastic lymphoma kinase gene rearrangement in non-small-cell lung cancer in a Brazilian population

Cited by 17 publications

References 42 publications

Mutational Profile and New IASLC/ATS/ERS Classification Provide Additional Prognostic Information about Lung Adenocarcinoma: A Study of 125 Patients from Brazil

Mutational Profile and New IASLC/ATS/ERS Classification Provide Additional Prognostic Information about Lung Adenocarcinoma: A Study of 125 Patients from Brazil

Molecular Epidemiology of <b><i>ALK</i></b> Rearrangements in Advanced Lung Adenocarcinoma in Latin America

Anaplastic lymphoma kinase gene rearrangement and non-small cell lung cancer management: a step forward in personalized therapy

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