AKR1B10 in usual interstitial pneumonia: expression in squamous metaplasia in association with smoking and lung cancer.
The incidence of lung cancer (LC) is markedly increased among patients with usual interstitial pneumonia (UIP), and tobacco smoking is its superimposed risk factor. AKR1B10 (aldo-keto reductase 1B10) is frequently overexpressed in pulmonary squamous cell carcinoma and adenocarcinoma in smokers. To investigate the role of AKR1B10 in the pulmonary carcinogenesis in UIP with correlation to tobacco smoking, we examined 13 UIP cases with LC, 13 UIP cases without LC, and 30 cases of non-UIP LC using AKR1B10 immunohistochemistry. AKR1B10 immunoreactivity was confined to squamous metaplasia in honeycomb lesions of UIP and neoplastic cells of LC. Squamous metaplastic foci showed AKR1B10 immunoreactivity more frequently in UIP with LC (24/36 foci, 67%) than in UIP without LC (16/44 foci, 37%) (P<0.01). AKR1B10 expression in UIP was also more frequent in squamous metaplastic foci in smokers (38/67 foci, 57%) than in non-smokers (2/13 foci, 15%) (P<0.01). AKR1B10 expression was frequently observed in both UIP-associated LC (10/13 foci, 77%) and non-UIP LC (18/30 foci, 60%). Ki-67 labeling index was significantly higher in AKR1B10-positive squamous metaplasia of UIP than in AKR1B10-negative squamous metaplasia of UIP. Our results demonstrate that AKR1B10 is involved in the development of LC in UIP in association with smoking. AKR1B10 might be useful as a new marker for identification of high LC risk patients in UIP.
Li
Chih-Ping
CP
Department of Human Pathology, Graduate School of Medicine, The University of Tokyo, Hongo 7-3-1, Bunkyo-ku, Tokyo 113-0033, Japan.
Goto
Akiteru
A
Watanabe
Akira
A
Murata
Kengo
K
Ota
Satoshi
S
Niki
Toshiro
T
Aburatani
Hiroyuki
H
Fukayama
Masashi
M
D000230:Adenocarcinoma / Q000201:enzymology / Q000209:etiology* / Q000473:pathology; D000368:Aged; D000369:Aged, 80 and over; D000449:Aldehyde Reductase / Q000032:analysis*; D000074408:Aldo-Keto Reductases; D014408:Biomarkers, Tumor / Q000032:analysis*; D002294:Carcinoma, Squamous Cell / Q000201:enzymology / Q000209:etiology* / Q000473:pathology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007564:Japan; D019394:Ki-67 Antigen / Q000032:analysis; D017563:Lung Diseases, Interstitial / Q000150:complications / Q000201:enzymology* / Q000473:pathology; D008175:Lung Neoplasms / Q000201:enzymology / Q000209:etiology* / Q000473:pathology; D008297:Male; D008679:Metaplasia; D008875:Middle Aged; D020545:Respiratory Mucosa / Q000201:enzymology* / Q000473:pathology; D012307:Risk Factors; D012907:Smoking / Q000009:adverse effects*; D016159:Tumor Suppressor Protein p53 / Q000032:analysis
D014408:Biomarkers, Tumor; D019394:Ki-67 Antigen; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; C120471:AKR1B10 protein, human; D000074408:Aldo-Keto Reductases; D000449:Aldehyde Reductase