Genetic and Immunohistochemical Profiling of Lung Cancer in Young Adults
N Motoi, H Nagano, K Nomura, Y Ishikawa, M Arai. Japanese Foundation for Cancer Research, Kotoku, Tokyo, Japan; Cancer Instituite Hospital, Kotoku, Tokyo, Japan
Background: The clinical features and phenotype of lung cancers can be strongly influenced by the underlying oncogenic molecular alterations. The goal of this study is to clarify the molecular alterations in lung cancer (LC) of young adults as a possible model of lung carcinogenesis, and to evaluate clinical relevance of molecular subtypes.
Design: Young adults' lung cancer (YLC) was defined as a LC occurring at the age below the average - 2 SD of all primary LC during 1987-2007 at our institution (i.e. 46 year old). Clinical data were collected from the medical record. YLC under the age of 40 were further analyzed for mutational status and immunohistochemical (IHC) profiles. EGFR and KRAS mutations were screened by high resolution melting method and confirmed by sequencing. IHC was performed for TP53 and ALK.
Results: Of all 2827 LCs, 173 YLCs were identified (6.1%), with 91 males and 82 females (39 and 33, respectively in the group of under 40 year old). Almost all the patients were no or light smokers. Adenocarcinoma (AD) was the most common histologic subgroup (n=55), followed by squamous cell carcinoma (SQ, n=6), small cell carcinoma (4), carcinoid (4) and large cell carcinoma (3). Among AD, BAC (7) and salivary gland type-AD (7) were the most common subtypes. Genetic analysis revealed 7 AD with EGFR mutations with preference of histologic BAC subtype. One AD (BAC) developed in the patient with Li-Fraumeni syndrome with TP53 germline mutation. All the studied cases showed wild type KRAS. IHC showed strong expression of ALK in 8 AD (14.5% of all AD), with preference of acinar and papillary subtypes. Overexpression of p53 was observed in 23 cases; 19 AD (34.5% of AD) and 4 SQ (66.7% of SQ). Five of EGFR-mutated AD showed overexpression of p53. Two AD showed both ALK and p53 expression. In summary, YLC showed higher incidence of EGFR and ALK alteration as compared to the older population. Of these changes, some EGFR or ALK alteration occurred with simultaneous p53 overexpression. KRAS mutation in YLC was exceptional.
Conclusions: Our data suggest that there are distinct genetically characterized subgroups in YLC. In addition, each of these subgroups seems to show different histopathologic features and immunohistochemical profiles. Although further validation is needed, this study suggests that molecular and clinicopathologic features may be combined to provide clinically and therapeutically relevant classification of lung cancer, especially in young population.
Tuesday, March 10, 2009 1:00 PM
Poster Session IV # 225, Tuesday Afternoon