Roles of human epidermal growth factor receptor family in pulmonary lymphangioleiomyomatosis.

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.

• Authors: Kazuma Kobayashi, Yasuhiro Miki, Ryoko Saito, Koko Adachi, Kuniaki Seyama, Yoshinori Okada, Hironobu Sasano
• Journal: Human pathology (Hum Pathol) Vol. 81 Pg. 121-130 (11 2018) ISSN: 1532-8392 [Electronic] United States
• PMID: 30030119 (Publication Type: Journal Article)
• Copyright: Copyright © 2018 Elsevier Inc. All rights reserved.

Chemical References

• EGFR protein, human
• ERBB2 protein, human
• ERBB3 protein, human
• ERBB4 protein, human
• ErbB Receptors
• Receptor, ErbB-2
• Receptor, ErbB-3
• Receptor, ErbB-4

Topics

• Adult
• Age Factors
• Cell Line, Tumor
• ErbB Receptors (genetics, metabolism)
• Female
• Gene Expression Regulation, Neoplastic
• Humans
• Immunohistochemistry
• Lung Neoplasms (chemistry, diagnosis, genetics, surgery)
• Lymphangioleiomyomatosis (diagnosis, genetics, metabolism, surgery)
• Middle Aged
• Prognosis
• Receptor, ErbB-2 (genetics, metabolism)
• Receptor, ErbB-3 (genetics, metabolism)
• Receptor, ErbB-4 (genetics, metabolism)
• Reverse Transcriptase Polymerase Chain Reaction
• Risk Factors
• Signal Transduction
• Tissue Array Analysis