Molecular profile of non-small cell lung cancer in northeastern Brazil

Abstract

Objective: To investigate the histological subtypes and mutational profiles of non-small cell lung cancer in Brazil, looking for correlations among histological subtypes, expression of anaplastic lymphoma kinase (ALK), EGFR mutation status, and programmed death-ligand 1 (PD-L1) expression. Methods: We evaluated 173 specimens obtained from patients with lung adenocarcinoma in northeastern Brazil. Expression of PD-L1 and ALK was evaluated by immunohistochemistry; EGFR mutation status was evaluated by sequencing. We categorized the histological subtypes in accordance with the International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society classification. Results: The most common histological subtypes of lung adenocarcinoma were solid predominant (in 46.8%), acinar predominant (in 37.0%), and lepidic predominant (in 9.8%). ALK expression was detected in 10.4% of the samples, and 22.0% of the tumors harbored EGFR mutations. The most common EGFR mutation was an exon 21 L858R point mutation (in 45.5%), followed by an exon 19 deletion (in 36.3%). The tumor proportion score for PD-L1 expression was ≥ 50% in 18.2% of the samples, 1-49% in 32.7%, and 0% in 49.5%. The solid predominant subtype was significantly associated with wild-type EGFR status (p = 0.047). Positivity for PD-L1 expression was not found to be significantly associated with ALK expression or EGFR mutation status. Conclusions: Our results suggest that the molecular profile of non-small cell lung cancer in northeastern Brazil differs from those of populations in other regions of the country, with ALK positivity being higher than the other biomarkers. Further studies including clinical and genetic information are required to confirm these differences, as well as studies focusing on populations living in different areas of the country.

Glycogen Synthase Kinase-3 Beta Expression Correlates With Worse Overall Survival in Non-Small Cell Lung Cancer—A Clinicopathological Series

“…Despite the theoretical rationale supporting this association, we did not identify a relationship between PDL1 and GSK-3b scores in our cohort. A recent publication about the positivity of PDL1 in the same region of northeastern Brazil showed that 59.5% of patients were PDL1 negative (43). Matsuo et al studied the importance of AKT, mTOR, and GSK3 in the occurrence of lymph node involvement in oral cavity squamous cell carcinomas.…”

Simultaneous analysis of ALK, RET, and ROS1 gene fusions by NanoString in Brazilian lung adenocarcinoma patients

“…In Latin America, a study enrolling 5,130 NSCLC patients from 10 countries (excepting Brazil), the frequencies of ALK rearrangements ranged from 4.1% to 10.8% (Colombia 4.1%; Panama 4.4%; Uruguay 5.4%; Argentina 6.0%; Mexico 7.6%; Chile 8.6%; Venezuela 8.9%; Costa Rica 9.5%; Peru 10.8%) (34). In Brazil, two recent studies employing immunohistochemistry, one from Northeast and another from South, reported frequencies of ALK rearrangements of 10.4% (n=173 patients) and 4% (n=275 patients), respectively (10,12). The frequency of ALK rearrangements in the present work is in between other Brazilian studies.…”

“…Other driver genomic alterations are ALK, RET, and ROS1 rearrangements, which can also be targeted for tyrosine kinase inhibitors (TKIs) (2,9). Although these genetic rearrangements are actionable, and the frequency of them is broadly investigated worldwide, the frequency of RET and ROS1 rearrangements is unknown in Brazilian patients (10)(11)(12). Moreover, Brazilian patients have a high admixture background, with contribution from European, African, Native American (Amerindian), and, more recently, Asian ethnicities (8,13,14).…”

Testing for EGFR Mutations and ALK Rearrangements in Advanced Non-Small-Cell Lung Cancer: Considerations for Countries in Emerging Markets

“…Similarly, some laboratories prefer NGS technologies, [162][163][164] sequencing 14-20 genes at one time, 124,162,165 whereas others have adopted strategies to improve TAT by using RT-PCR assays for EGFR and BRAF mutations, 162,[164][165][166] and IHC/FISH for ALK, ROS1 and PD-L1 rearrangements. 163,164,167 In the absence of government reimbursement for molecular testing, several pharmaceutical companies have recently established a national "Lung Mapping" consortium. The consortium provides oncologists with access to a subsidized NGS-based test using the FoundationOne ® platform and has considerably improved access to testing in several Brazilian centers.…”