Roles of human epidermal growth factor receptor family in pulmonary lymphangioleiomyomatosis

Kazuma Kobayashi, Yasuhiro Miki, Ryoko Saito, Koko Adachi, Kuniaki Seyama, Yoshinori Okada, Hironobu Sasano

Research output: Contribution to journalArticlepeer-review

1 Citation (Scopus)

Abstract

Lymphangioleiomyomatosis (LAM) is a rare and refractory disease that affects women of reproductive age. Several target therapies are used to manage LAM, but no curative modes of treatment have been reported yet. Therefore, in this study, we focused on targeting human epidermal growth factor receptor (HER) family proteins as a treatment strategy for LAM. In antibody array analysis, HER signaling was detected in the proteins extracted from LAM tissues. We then evaluated the expression of HER family members in 34 pulmonary LAM specimens using both immunohistochemistry and quantitative reverse-transcription polymerase chain reaction. Hierarchical clustering analysis was performed to classify the cases based on the immunohistochemistry results. Both epidermal growth factor receptor (EGFR) and HER4 were expressed in all 34 cases. HER3 was expressed in 25 of 34 cases, but HER2 was not expressed in any case. In addition, results of quantitative reverse-transcription polymerase chain reaction analysis confirmed the expression of EGFR and HER4 expression in LAM cells. Patients with HER3- or HER4-positive tissues were younger and had a history of pneumothorax. The cases were classified into 4 different clusters based on the results of hierarchical cluster analysis. One of these clusters was associated with EGFR, HER3, and HER4; the patients in this cluster were significantly younger and had a history of pneumothorax. These results indicated that HER family could contribute to the progression of pulmonary LAM, and treatments targeted against HER family might be effective for treating pulmonary LAM.

Original languageEnglish
Pages (from-to)121-130
Number of pages10
JournalHuman Pathology
Volume81
DOIs
Publication statusPublished - 2018 Nov

Keywords

  • EGFR
  • HER2
  • HER3
  • HER4
  • Lymphangioleiomyomatosis

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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