Lung Adenocarcinoma in Young Adults: EGFR/KRAS/ALK Mutation Status and Clinicopathological Features in 64 Patients under Age 40.
Snjezana Dogan, Suresh C Jhanwar, Marc Ladanyi, Maureen F Zakowski. Memorial Sloan-Kettering Cancer Center, New York, NY
Background: Lung cancer in patients <40 years old is rare and adenocarcinoma is the most common histological type. Poor outcomes and the availability of targeted therapies prompt the need for an accurate clinicopathological and molecular characterization of adenocarcinomas occurring in this age group. Here, we evaluated 64 consecutive lung adenocarcinoma cases from patients under age 40.
Design: From 09/2004 to 03/2010, 64 lung adenocarcinomas arising in patients 15-39 years old were tested for EGFR mutations (exon 19 del and L858R mutation in exon 21) using sensitive mutation-specific PCR assays, KRAS mutations (codon 12 and 13 in exon 2) by PCR-sequencing, and EML4-ALK rearrangement by FISH. Of 64 cases, 63 and 47 cases had sufficient material for EGFR/KRAS and ALK testing, respectively. H&E histology and/or cytology slides were reviewed and 56 tumors were histologically categorized as (1) well-, (2) moderately- & moderately to poorly-, and (3) poorly differentiated. Differentiation could not be determined in 8 cases due to scant material. Clinical data on 2964 lung adenocarcinoma patients over age 40 were used for comparison. Associations were tested using the Fisher exact test.
Results: Among these 64 patients, there were 34 (53%) women and 30 (47%) men including 39 (61%) never smokers. Nine of 63 (14%) had EGFR mutations (8 exon 19 del and 1 L858R), and 10/63 (16%) had KRAS mutations (5 G12D, 2 G12V, 1 G12C, 1 G12A, and 1 G13D). EML4-ALK translocation was detected in 7 of 47 (15%) cases. Poorly differentiated tumors were more frequent in men than in women (16/25; 64% vs. 9/31; 29%, p=0.01). Twelve of 34 (35%) women and none of 30 men presented at stage I (p=0.0002). In comparison to older male patients, men under 40 were more likely to present at stage IIIB/IV (25/30; 83% vs. 633/1099; 58%, p=0.004), and were less likely to present at stage I (0/30; 0% vs. 299/1099; 27%, p=0.0002).
Conclusions: In this subset of patients with lung adenocarcinoma, the high proportion of never smokers suggests an etiology unrelated to tobacco, also supported by the very low prevalence of the smoking-associated KRAS G12C mutation and the relative frequency of the KRAS G12D mutation typically seen in never smokers. A relatively high percentage of EML4-ALK rearrangement in these patients may warrant EML4-ALK detection as a first-line/high-priority molecular test in this age group. A relatively higher frequency of late stage at presentation and a higher likelihood of poorly differentiated adenocarcinomas in men <40 may imply more aggressive tumor biology.
Tuesday, March 1, 2011 1:00 PM
Poster Session IV # 267, Tuesday Afternoon