Epidermal development Factor Receptor Mutation in Lung Adenocarcinomas Relationship with CT Characteristics and Histologic Subtypes

  • From the Departments of Radiology (H.J.L.) and Pathology (Y.K.J., D.H.C.), Seoul nationwide University Hospital, 28 Yeongeon-dong, Chongno-gu, Seoul 110-744, Republic of Korea; Department of Thoracic and Cardiovascular Surgery, Seoul National University Hospital, Cancer analysis Institute, Xenotransplantation analysis Center, Clinical analysis Center, Seoul National University College of Medicine, Seoul, Republic of Korea (Y.T.K., C.H.K.); Department of Clinical Radiology, University Hospital MГјnster, MГјnster, Germany (T.P.); and Department of Radiology, Columbia University Medical Center, New York, NY (B.Z., Y.T., L.H.S., T.P.).
  • Address communication to H.J.L. (e-mail [email protected] ).

Abstract

Function

To retrospectively recognize quantitative computed tomographic (CT) features that correlate with epidermal growth factor receptor (EGFR) mutation in surgically resected lung adenocarcinomas stratified by the Global Association for the research of Lung Cancer (IASLC), United states Thoracic Society (ATS), and European breathing Society (ERS) category in an eastern Asian cohort of patients known to have high prevalence of EGFR mutations.

Materials and techniques

An institutional review board approved this research and waived consent that is informed. In 153 surgically resected lung adenocarcinomas, EGFR mutation ended up being dependant on direct DNA sequencing. Histologic subtype had been classified based on IASLC/ATS/ERS category of lung adenocarcinoma. At preoperative chest CT, the portion of ground-glass opacity (GGO) amount and total cyst level of each cyst were calculated with a semiautomated algorithm. Circulation of EGFR mutation in accordance with histologic subtype, portion of GGO amount, and total tumor volume had been examined utilizing the Fisher exact test, the Student t test, trend analysis, and multiple logistic regression analysis.

Outcomes

Exon 21 missense mutation had been more regular in lepidic predominant adenocarcinomas than in other histologic subtypes (chances ratio, 3.44; 95% self- confidence interval 1.53, 7.74; P = .003). GGO amount percentage in tumors with exon 21 missense mutation (61.7% ± 31.9 [standard deviation]) had been significantly greater than that in EGFR wild-type tumors (30.0per cent ± 38.5) (P = .0001) and exon 19–mutated tumors (28.9per cent ± 37.7) (P = .0006). of exon 21 missense mutation increasing along with increasing GGO volume (P = .0008) had been found.

Conclusion

GGO amount percentage in tumors with exon 21 missense mutation had been notably higher than that in tumors with other EGFR mutation status. This is often pertaining to the truth that exon 21 missense mutation was significantly more regular in lepidic predominant adenocarcinomas, including adenocarcinoma in situ, minimally invasive adenocarcinoma, and lepidic predominant invasive adenocarcinoma, according to IASLE/ATS/ERS classification.

Introduction

Epidermal development element receptor (EGFR) mutations are correlated with specific traits, such as nonsmoking status, adenocarcinoma histologic findings, female intercourse, and eastern Asian ethnicity (1,2). In turn, EGFR mutations are closely connected with a high reaction price to treatment with EGFR tyrosine kinase inhibitors (2–4). Recently, the relevant question of whether exon 19 removal and exon 21 L858R missense mutation, the two most typical forms of EGFR mutation, display distinctions in tumefaction characteristics was raised (5). Having said that, EGFR amplification is reported that occurs invariably on mutated and allele that is not–wild-type to be associated with solid histologic findings of adenocarcinoma, advanced level clinical stage, and dramatically even worse disease-free success (6,7).

Lung adenocarcinoma is the most typical histologic subtype of lung cancer tumors generally in most nations (8). In the decade that is past numerous improvements have taken spot in oncology, molecular biology, pathologic examination, radiology, and surgery of lung adenocarcinoma. An international multidisciplinary classification system sponsored by the International Association for the Study of Lung Cancer (IASLC), American Thoracic Society (ATS), and European Respiratory Society (ERS) was proposed (9) with this background. In this brand new classification, there are many changes for surgically resected tumors (a) The word bronchioloalveolar carcinoma is no longer utilized, and it is now to be referred to as lepidic pattern. (b) The word adenocarcinoma in situ is proposed for tiny (≤3 cm) solitary adenocarcinomas with pure lepidic growth without intrusion. (c) Minimally invasive adenocarcinoma is proposed for little (≤3 cm) lepidic prevalent tumors with intrusion of 0.5 cm or less. (d) Invasive adenocarcinomas ought to be classified based on the prevalent subtype after semiquantitative assessment, such as for instance acinar predominant, papillary predominant, micropapillary predominant, solid predominant, and lepidic predominant adenocarcinoma that is invasive. (e) Micropapillary predominant invasive adenocarcinoma is usually to be added as being a major subtype. (f) Former mucinous bronchioloalveolar carcinomas are to be now categorized as invasive adenocarcinomas that are mucinous.

To the knowledge, just a studies that are few attempted to correlate imaging features with molecular findings. Recognition associated with the relationship between computed pop over to this web-site tomographic (CT) imaging traits and EGFR molecular status can help define categories of lung adenocarcinoma that have distinct medical, radiologic, molecular, and pathologic characteristics. Consequently, the objective of this study was to retrospectively identify quantitative CT features that correlate with EGFR mutation status in surgically resected lung adenocarcinomas stratified by IASLC/ATS/ERS category in a East Asian cohort of patients known to have high prevalence of EGFR mutations.

Materials and Methods

This research had been authorized by the Institutional Review Board of Seoul nationwide University Hospital. Informed consents for tissue collection and gene analyses for research purposes were obtained from individual clients before surgery in line with the policy of this Lung Cancer Tissue Bank for the Cancer Research Institute of Seoul National University.

Patient Selection

Among 161 consecutive clients who underwent surgical resection for primary lung adenocarcinoma at Seoul National University Hospital in Korea from October 2007 to October 2008, 153 clients (mean age, 63 years ± 10 [standard deviation]; age groups, 34–85 years; 73 men [mean age, 62 years ± 10; a long time, 36–85 years], 80 ladies [mean age, 63 years ± 10; a long time, 34–81 years]) had been most notable study on the basis of the accessibility to pathologic records for EGFR mutation and EGFR gene content quantity in resected specimens. Lobectomy ended up being performed in 143 clients, pneumonectomy in one, segmentectomy in one, and wedge resection in eight. The pathologic that is final cancer stages according to the seventh version Union for International Cancer Control and United states Joint Committee on Cancer TNM category (10,11) had been stage IA in 91 clients (59.5%), phase IB in 21 (13.7%), phase IIA in eight (5.3%), phase IIB in six (3.9%), and phase IIIA in 27 (17.6%).