Original contributionMolecular alterations in non–small cell lung carcinomas of the young☆
Introduction
Lung cancer is the leading cause of cancer death in the United States. Non–small cell lung carcinoma (NSCLC) constitutes 85% to 90% of all lung carcinomas with a median patient age of 70 years old [1]. Mutations in epidermal growth factor receptor (EGFR), KRAS, anaplastic lymphoma kinase (ALK), and BRAF affect the prognosis and treatment of lung adenocarcinoma. The frequencies of these alterations are associated with different patient factors, such as smoking history, sex, race, and age [2], [3], [4], [5], [6], [7]. However, because most lung cancers occur in patients older than age of 50 years, few studies have examined molecular alterations present in a younger cohort [2], [3].
Malignancies affecting young adults can differ significantly from those that arise in older adults. These include differences in tumor morphology, molecular alterations, prognosis, and response to treatment [2], [3], [8], [9], [10], [11]. Excluding pediatric malignancies, a significant risk factor for many cancers is age, and malignancy is rare in adults below the age of 50 years [1]. However, a cancer diagnosis in this group can be particularly devastating, often leading to a greater loss of longevity and quality of life for a given individual [12]. Although inherited genetic syndromes can result in malignancy at an earlier age, for many malignancies, it is unknown which factors contribute most to their early development.
The recently established molecular alterations in lung adenocarcinoma not only provide an understanding of tumorigenesis but are also strongly connected with patient prognosis and treatment. In this retrospective study, we examine the frequency of ALK, KRAS, EGFR, and BRAF mutations in 53 patients who developed NSCLC at or below the age of 50 years.
Section snippets
Database search
Permission to conduct the study and an informed consent waiver were obtained from the institutional review board. The pathology database was searched for patients below the age of 50 years old with NSCLC who underwent testing for EGFR, ALK, KRAS, and/or BRAF gene alterations. A total of 57 cases were identified, 53 of which were ultimately diagnosed as NSCLC. The cases spanned a period of approximately 4 years, from January 2010 to 2014.
Molecular testing before February 2013
All specimens were clinical samples submitted to our
Description of the study population
Fifty-three cases of NSCLC in patients age of 50 years or younger were identified in the pathology database (Table 1, Table 2). There was a predominance of women (64%). The average patient age at the time of diagnosis was 44.4 years, with a range between ages of 28 and 50 years old. Most patients were white (60%) or black (28%), with only 1 Asian patient (2%) and 5 patients of another or unknown race (10%). Patients with a greater than 5 pack-year history of smoking comprised 53% of all
Discussion
Activating EGFR mutations are most commonly found in nonsmokers, women, and patients of Asian descent. EGFR mutations are often associated with lepidic growth and a micropapillary pattern on histology [16], but histology is a poor predictor of mutation (Fig. 2C and D). Patients with activating EGFR mutations can be treated with EGFR tyrosine kinase inhibitors (TKI) [17]. When patients of all ages are considered, various studies have demonstrated EGFR mutation frequencies between 2% and 20% in
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Competing interests: Dr Ettinger is a consultant for Gilead, Foster city, CA, USA, Roche/Genetech, San Francisco, CA, USA, Boehringer Ingelheim, Fremont, CA, USA, Biodesix, Boulder, CO, USA, Lilly, Indianapolis, IN, USA, and Helsinn Pharmaceutical, Mulhuddart, Dublin, Germany. There are no additional current financial disclosures from any other authors. No payment or support was received for any aspect of the submitted work. The authors have no conflicts of interest to report.