Intratumoral distribution of EGFR-amplified and EGFR-mutated cells in pulmonary adenocarcinoma

Shingo Soma, Koji Tsuta, Toshimi Takano, Yutaka Hatanaka, Akihiko Yoshida, Kenji Suzuki, Hisao Asamura, Hitoshi Tsuda

Research output: Contribution to journalArticlepeer-review

4 Citations (Scopus)


Alterations in the epidermal growth factor receptor (EGFR) gene are associated with carcinogenesis in non-small cell lung cancer. However, the intratumoral distribution of these abnormalities has not been elucidated.This study included patients with surgically resected lung adenocarcinoma. The predominant histological growth pattern was determined. Chromogenic in situ hybridization (CISH) and EGFR-mutation specific-antibodies were used for analysis of changes in gene copy number and EGFR mutations, respectively.EGFR mutation detected immunohistochemistry (IHC) and amplification were identified in 31 (53%) and 30 (52%) cases, respectively. The predominant growth patterns in the 58 tumors evaluated were papillary (28, 48%), lepidic (8, 14%), acinar (15, 26%), and solid (7, 12%). EGFR mutations were the least common in cases with a solid predominant pattern. The incidence of EGFR amplification did not differ among predominant patterns. Analyzing each histological subtype, no differences were noted between the prevalence of EGFR-IHC positive and CISH-positive rates. In the analysis of EGFR amplification, CISH-positive status was more prevalent in IHC-positive cases than in IHC-negative cases. All 19 cases that were both IHC and CISH positive were analyzed. In 17 cases (90%), the IHC-positive area was equal to or larger than the CISH-positive area.Among the histological subtypes of lung adenocarcinoma, the solid predominant subtype was distinguishable by its infrequent EGFR mutations. EGFR gene mutations preceded changes in oncogenic drive, more so than did EGFR gene number alterations during the developmental process of lung adenocarcinoma.

Original languageEnglish
Pages (from-to)155-160
Number of pages6
JournalPathology Research and Practice
Issue number3
Publication statusPublished - 2014 Mar
Externally publishedYes


  • Adenocarcinoma of the lung
  • Chromogenic in situ hybridization
  • Epidermal growth factor receptor

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Cell Biology


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