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Int J Clin Exp Pathol 2013;6(1):1-12

Original Article
Downregulation of ALDH1A1 expression in non-small cell lung carcinomas – its
clinicopathologic and biological significance

Koji Okudela, Tetsukan Woo, Hideaki Mitsui, Takeshisa Suzuki, Michihiko Tajiri, Yuji Sakuma, Yohei Miyagi, Yoko Tateishi, Shigeaki Umeda,
Munetaka Masuda, Kenichi Ohashi

Department of Pathology and Surgery, Yokohama City University Graduate School of Medicine, 3-9, Fukuura, Kanazawa-ku, 236-0004,
Yokohama, Japan; Division of General Thoracic Surgery, Kanagawa Prefectural Cardiovascular and Respiratory Center Hospital, 6-16-1,
Tomioka-higashi, Kanazawa-ku, 230-0051, Yokohama, Japan; Clinical Research Institute, Kanagawa Prefectural Cancer Center Hospital, 1-1-
2, Nakako, Asahi-ku, 241-8515, Yokohama, Japan

Received October 4, 2012; Accepted November 1, 2012; Epub November 20, 2012; Published January 1, 2013

Abstract: ALDH1A1 metabolizes a variety of endogenous and exogenous aldehyde, and also oxidizes retinol to synthesize retinoic acid and
modulate cell differentiation. Moreover, ALDH1A1 is also suggested to participate in the maintenance of cancer stem cells. To investigate the
potential role of ALDH1A1 in carcinogenesis of the lung, the present study examined two hundred and sixty eight cases of non-small cell lung
carcinoma (NSCLC) for its immunohistochemical expression and analyzed associations between ALDH1A1 levels and a series of
clinicopathologic parameters. Also, the biological significance of the aberrant expression of ALDH1A1 was investigated in vitro. ALDH1A1
expression was markedly reduced in 39.9% (107/268) of NSCLCs. The incidence of this reduction was significantly higher in
adenocarcinomas (ADC: 41.6%, 85/207) and large cell carcinomas (61.1%, 11/18) than squamous cell carcinomas (25.5%, 11/43). Among
ADCs, the downregulation tended to be more remarkable in high grade, poorly differentiated tumors, and tumors with stronger proliferating
activity. It also occurred with a significantly higher incidence in smokers than non-smokers. Forced expression of ALDH1A1 in NSCLC cell
lines, which had lost ALDH1A1 expression, markedly attenuated their growth. Taken together, loss of ALDH1A1 expression is suggested to
promote carcinogenesis especially in the smoking-related ADCs. (IJC1210003).

Keywords: Non-small cell lung carcinoma, ALDH1A1, immunohistochemistry, tumor suppressor, smoking, cancer stem cell

Address all correspondence to:
Dr. Koji Okudela
Department of Pathology, Yokohama City University
Graduate School of Medicine
3-9, Fukuura, Kanazawa-ku, 236-0004
Yokohama, Japan.
Phone: +81-45-787-2583; Fax: +81-45-789-0588
E-mail: kojixok@yokohama-cu.ac.jp