Unique expression profiles of mucin proteins in interstitial pneumonia-associated lung adenocarcinomas

Toshiaki Kataoka¹, Koji Okudela¹, Yu Nakashima¹, Hideaki Mitsui¹, Mai Matsumura¹, Shigeaki Umeda¹, Hiromasa Arai^2,3, Tomohisa Baba⁴, Takehisa Suzuki¹, Chihiro Koike¹, Yoko Tateishi¹, Michihiko Tajiri³, Tamiko Takemura⁵, Takashi Ogura⁴, Munetaka Masuda² and Kenichi Ohashi¹

Department of ¹Pathology and ²Surgery, Yokohama City University Graduate School of Medicine, Divisions of ³General Thoracic Surgery and ⁴Respiratory Medicine, Kanagawa Prefectural Cardiovascular and Respiratory Center Hospital, Tomioka-higashi, Kanazawa-ku, Yokohama and ⁵Division of Pathology, Japanese Red Cross Medical Center Hospital, Tokyo, Japan

Offprint requests to: Koji Okudela, M.D., Ph.D., Department of Pathology, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama, Japan. e-mail: kojixok@yokohama-cu.ac.jp

Summary. In order to clarify idiopathic interstitial pneumonia (IIP)-associated lung adenocarcinoma (LADC), we herein focused on the expression profiles of mucin proteins, the most common cellular differentiation markers. The expression of the mucin (MUC) 1, MUC2, MUC3B, MUC4, MUC5AC, MUC5B, MUC6, MUC7, MUC9, and MUC21 proteins was examined immunohistochemically and their levels were semi-quantified in 80 IIP-associated LADCs and 106 non-IIP LADCs. LADCs were divided into low and high expressers based on thresholds obtained from the receiver operating characteristic (ROC) curves of each mucin protein. Low expressers of MUC1, MUC7, and MUC21 and high expressers of MUC4, MUC5AC, MUC5B, and MUC9 were dominant in the IIP group. Multivariate analyses confirmed that the correlations between mucin expression profiles and IIP-associated LADCs were independent of putative confounding factors, such as smoking, gender, histological types, and cytological types. Thus, the expression profiles of these mucin proteins significantly differed between the IIP and non-IIP groups. IIP-associated LADCs appear to have unique cellular differentiation features and they may develop through a distinct histogenetic pathway. This is the first study to demonstrate that IIP-associated LADCs have unique mucin expression profiles. Histol Histopathol 34, 1243-1254 (2019)

Key words: Mucin, Immunohistochemistry, Interstitial pneumonia, Lung, Adenocarcinoma

DOI: 10.14670/HH-18-114