Elsevier

Lung Cancer

Volume 79, Issue 3, March 2013, Pages 242-247
Lung Cancer

Metabolic and metastatic characteristics of ALK-rearranged lung adenocarcinoma on FDG PET/CT

https://doi.org/10.1016/j.lungcan.2012.11.021Get rights and content

Abstract

Introduction

ALK rearrangement in lung cancer has been identified as a novel molecular target in lung adenocarcinoma. In this study, we evaluated metabolic and metastatic features of lung adenocarcinoma by using FDG PET/CT, with regard to specific genotypes of ALK and EGFR mutation.

Methods

Patients with lung adenocarcinoma initially diagnosed and examined with FDG PET/CT and molecular genotyping with biopsy specimen, from September 2009 to September 2011, were selected retrospectively. ALK fluorescence in situ hybridization and EGFR mutations were tested. Maximum standardized uptake value (SUVmax) and metastatic characteristics on FDG PET/CT were analyzed with regard to ALK and EGFR status.

Results

Of the 331 lung adenocarcinoma patients, 18 were ALK positive (ALK+), 156 were EGFR mutation positive (EGFR+), and 157 were wild type (WT) for both ALK and EGFR mutation. The ALK+ tumor showed significantly higher SUVmax and more common metastasis to lymph nodes and distant organs than those of other genotypes in overall patients (P < 0.01). In a subgroup analysis of advanced stage (stage IIIb and IV), ALK+ lung cancer showed significantly higher SUVmax (P < 0.05) than EGFR+ tumors. In another subgroup analysis of size matched groups, ALK+ tumors showed significant difference in SUVmax, lymph node and distant metastasis (P < 0.01), particularly in the moderate-sized tumors (1.5–3 cm).

Conclusion

ALK-rearranged lung adenocarcinoma represents higher glucose metabolism and more rapid metastasis to lymph nodes or distant sites compared with those with EGFR mutation and wild type, which suggests more aggressive features of ALK rearrangement.

Introduction

Lung cancer is the leading cause of cancer-related deaths worldwide in both men and women [1]. Non-small cell lung cancers account for about 85% of lung cancers [2], in which adenocarcinoma is the most common histopathological type in recent decades [3]. Lung adenocarcinomas are genetically heterogeneous diseases based on molecular profile studies [4]. Genetic studies have revealed several genetic alterations in lung adenocarcinoma [5], [6], [7], [8], [9], which may be specific targets for personalized therapy [10]. As an example, adenocarcinoma with a mutation in epidermal growth factor receptor gene (EGFR), which includes deletion of exon 19 and substitution of L858R in exon 21, is susceptible to EGFR-targeted tyrosine kinase inhibitors (TKIs) such as gefitinib or erlotinib [5], [11], [12]. Thus, EGFR mutations are a prognostic factor for good response to TKI treatment as well as for favorable clinical outcome [13].

Recently, a novel oncogene was identified in lung adenocarcinoma; echinoderm microtubule-associated protein like 4 (EML4)-anaplastic lymphoma kinase (ALK) fusion oncogene [9]. ALK rearrangement in lung adenocarcinoma is a marker for unique subtype, and mutually exclusive with EGFR mutations [9], [14]. ALK inhibitors have already been developed and demonstrated striking response in lung cancers with ALK rearrangement [15]. Thus ALK rearrangement in lung cancer is currently considered as an important biomarker for targeted molecular therapy, although it is not so frequent in lung adenocarcinoma.

18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) scan is currently one of essential imaging modalities in diagnosis and staging of lung cancers. Additionally, glucose metabolism of cancer tissues per se, which is measured on FDG PET/CT, is a significant biomarker for characterization of cancers. Many studies have reported correlations between FDG uptake and biologic features of cancers such as proliferation, histologic type, tumor differentiation, and hypoxia [16], [17], [18], [19], [20]. FDG uptake is also related with genetic alterations, and it was reported that lung cancers with EGFR mutation demonstrate different pattern of FDG uptake [21], [22], [23]. However, the correlation between glucose metabolism and ALK rearrangement has not been reported as long as we know, while clinicopathological features according to ALK rearrangement and EGFR mutation were reported in several studies [24], [25], [26], [27].

In the present study, we investigated metabolic and metastatic characteristics of lung adenocarcinoma using FDG PET/CT, with regard to ALK rearrangement or EGFR mutations.

Section snippets

Subjects and clinical factors

From September 2009 to September 2011, patients with lung adenocarcinoma who underwent FDG PET/CT for initial diagnosis were retrospectively selected from cancer database of our hospital. Among them, 331 patients had results of ALK rearrangement and EGFR mutation for pathologic specimens, and were included in the final analysis. For the patients, clinical data were obtained by review of medical records.

This study was approved by the Institutional Review Board.

Genetic study

Genetic alterations were tested

Correlation of genetic alterations with tumor metabolism and clinical factors

Among the 331 patients who were included in the analysis, 158 (47.7%) were male and 173 (52.3%) were female. Mean age was 62.2 ± 10.3 (range 14–85) years. In the test of genetic alteration, 18 (5.4%) were ALK+, 156 (47.1%) were EGFR+, and the other 157 (47.4%) were WT. Clinical characteristics of the overall group is summarized in Table 1.

In comparison between three groups of different genetic alteration, significant differences existed in sex, smoking status, tumor stage, size, and SUVmax of

Discussion

In the current study, we investigated metabolic and metastatic characteristics of lung adenocarcinomas using FDG PET/CT, with regard to ALK rearrangement or EGFR mutations. As a result, glucose metabolism was generally higher in ALK+ group, compared with EGFR+ or WT groups. Additionally, ALK+ group demonstrated more common metastasis to lymph nodes and distant organs, suggesting more aggressive features and more rapid disease progression related with ALK rearrangement.

Glucose metabolism of

Conclusion

ALK-rearranged lung adenocarcinoma is related with higher glucose metabolism and more common metastasis to lymph node and distant area compared with EGFR-mutated or wild type lung adenocarcinomas. It suggests aggressive features of ALK rearrangement. Further studies are warranted for comprehensive understanding of phenotypic expression of the gene alteration.

Conflict of interest statement

None declared.

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