Unique prevalence of oncogenic genetic alterations in young patients with lung adenocarcinoma.
Lung adenocarcinoma in the young is a rare entity, and the oncogenic genetic alterations (GAs) and clinical characteristics associated with this disease are poorly understood. Conversely, it has been demonstrated that young age at diagnosis defines unique biology in other cancers. For this report, the effects of young age on lung adenocarcinoma are reported.



The authors retrospectively screened 1746 consecutive patients who were diagnosed with stage I through IV adenocarcinoma between 2009 and 2015 and identified 81 who were aged 40 years or younger at diagnosis. The clinical and genetic characteristics of this younger population were analyzed.



Of the 81 younger patients identified, 36 (44%) were men, 36 (44%) were never smokers, and the median age was 36 years (range, 26-40 years). Thirty-three patients (41%) harbored anaplastic lymphoma kinase (ALK) translocations, 24 (30%) had epidermal growth factor receptor (EGFR) mutations, and 2 (2%) had v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS) mutations. Rare oncogenic GAs also were studied in patients who had wild-type ALK/EGFR/KRAS adenocarcinoma, including 4 patients with HER2 mutations, 2 with Ret proto-oncogene (RET) translocations, and 2 with ROS proto-oncogene 1 receptor tyrosine kinase (ROS1) translocations. Notably, oncogenic GAs (P < .001), ALK (P < .001) and ROS1 (P = .033) translocations, and HER2 mutations (P < .001) were associated with young age, and a similar trend was observed for RET translocations (P = .108). Younger patients who had adenocarcinoma without GAs had a significantly worse prognosis compared with older patients without GAs (overall survival, 8.9 vs 16.4 months; P < .001) and patients with GAs (24.9 months; P < .001).



Younger patients with adenocarcinoma have a distinctly unique prevalence of oncogenic GAs. Comprehensive oncogenic GA screening is especially recommended for personalized medicine strategies in this population. Cancer 2017;123:1731-1740. © 2017 American Cancer Society.
Department of Thoracic Oncology, Aichi Cancer Center Hospital, Nagoya, Japan.
Kosuke
K
Tanaka
Department of Thoracic Oncology, Aichi Cancer Center Hospital, Nagoya, Japan.
Toyoaki
T
Hida
Department of Thoracic Oncology, Aichi Cancer Center Hospital, Nagoya, Japan.
Yuko
Y
Oya
Department of Thoracic Oncology, Aichi Cancer Center Hospital, Nagoya, Japan.
Tatsuya
T
Yoshida
Department of Thoracic Oncology, Aichi Cancer Center Hospital, Nagoya, Japan.
Junichi
J
Shimizu
Department of Thoracic Surgery, Aichi Cancer Center Hospital, Nagoya, Japan.
Tetsuya
T
Mizuno
Department of Thoracic Surgery, Aichi Cancer Center Hospital, Nagoya, Japan.
Hiroaki
H
Kuroda
Department of Thoracic Surgery, Aichi Cancer Center Hospital, Nagoya, Japan.
Noriaki
N
Sakakura
Department of Biomedical Statistics, Innovative Clinical Research Center, Kanazawa University, Kanazawa, Japan.
Kenichi
K
Yoshimura
Department of Thoracic Oncology, Aichi Cancer Center Hospital, Nagoya, Japan.
Yoshitsugu
Y
Horio
Department of Thoracic Surgery, Aichi Cancer Center Hospital, Nagoya, Japan.
Yukinori
Y
Sakao
Department of Pathology and Molecular Diagnostics, Aichi Cancer Center Hospital, Nagoya, Japan.
Yasushi
Y
Yatabe
D000230:Adenocarcinoma / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology; D000077192:Adenocarcinoma of Lung; D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000077548:Anaplastic Lymphoma Kinase; D066246:ErbB Receptors / Q000235:genetics; D005260:Female; D050939:Gene Fusion; D006801:Humans; D008175:Lung Neoplasms / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009367:Neoplasm Staging; D011379:Prognosis; D011505:Protein-Tyrosine Kinases / Q000235:genetics; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins / Q000235:genetics; D051096:Proto-Oncogene Proteins c-ret / Q000235:genetics; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics; D012189:Retrospective Studies; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012907:Smoking / Q000453:epidemiology; D015996:Survival Rate; D014178:Translocation, Genetic
D000077548:Anaplastic Lymphoma Kinase; D066246:ErbB Receptors; D011505:Protein-Tyrosine Kinases; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; D051096:Proto-Oncogene Proteins c-ret; D016283:Proto-Oncogene Proteins p21(ras); D020794:Receptor Protein-Tyrosine Kinases; D018719:Erb-b2 Receptor Tyrosine Kinases; C117307:KRAS protein, human; C000715470:MAS1 protein, human; C000626173:ALK protein, human; C000626175:Alk protein, rat; C512478:EGFR protein, human; C508053:ERBB2 protein, human; C099282:RET protein, human; C062333:ROS1 protein, human
ROS proto-oncogene 1 receptor tyrosine kinase (ROS1); Ret proto-oncogene (RET); anaplastic lymphoma kinase (ALK); driver oncogene; human epidermal growth factor receptor 2 (HER2); lung adenocarcinoma; young age