Prognostic significance of HE4 expression in pulmonary adenocarcinoma

• Published in: Tumor biology Vol. 32; no. 2; pp. 265 - 271
• Main Authors: Yamashita, Shin-ichi, Tokuishi, Keita, Hashimoto, Takafumi, Moroga, Toshihiko, Kamei, Mirei, Ono, Kiyoshi, Miyawaki, Michiyo, Takeno, Shinsuke, Chujo, Masao, Yamamoto, Satoshi, Kawahara, Katsunobu
• Format: Journal Article
• Language: English
• Published: Dordrecht Springer Netherlands 01.04.2011; Springer Nature B.V
• Subjects: Adenocarcinoma - diagnosis; Adenocarcinoma - metabolism; Adenocarcinoma - mortality; Aged; beta-Defensins; Biomarkers, Tumor - metabolism; Biomedical and Life Sciences; Biomedicine; Cancer Research; Case-Control Studies; Epididymal Secretory Proteins - metabolism; Female; Gene expression; Humans; Lung cancer; Lung Neoplasms - diagnosis; Lung Neoplasms - metabolism; Lung Neoplasms - mortality; Male; Medical prognosis; Middle Aged; Prognosis; Proportional Hazards Models; Proteins; Regression Analysis; Research Article; Retrospective Studies; Survival Rate; Adenocarcinoma; Prognosis; Lung; HE4; WFDC2
• ISSN: 1010-4283; 1423-0380
• DOI: 10.1007/s13277-010-0118-5

We investigated the possibility of human epididymis 4(HE4) to predict survival for patients with pulmonary adenocarcinoma. One hundred and thirty-seven patients with pulmonary adenocarcinoma underwent surgery in our institute from 2000 to 2008. We used immunohistochemical analysis to determine the expression of HE4 and compared with the clinicopathological factors and survival. Serum levels of HE4 in lung adenocarcinoma were investigated by enzyme immunometric assay. Fifty-seven of 137 cases (41.6%) were HE4 positive. It was found that there was no correlation between HE4 expression by immunohistochemistry and clinicopathological factors, however, adenocarcinoma subtype was significantly associated with HE4 expression. Sera in lung adenocarcinoma were significantly higher than in healthy control. Five-year disease-free survival in the HE4-positive group (44.6%) was significantly different from that in the negative group (82.3%, p  = 0.001) by immunohistochemistry. The five-year overall survival rate was 60.1% in the HE4-positive group, as compared with 90.8% in the HE4-negative group ( p  = 0.001). In multivariate Cox regression analysis, positive HE4 protein expression was a worse prognosis factor of disease-free and overall survival (HR = 3.7, 95%CI = [1.7–8.4], p  = 0.001; HR = 5.5, 95%CI = [1.8–17.2], p  = 0.003, respectively), in addition to nodal status as a powerful value. When HE4 expression in adenocarcinoma cases except the BAC were analyzed, nodal status and HE4 expression were independent prognostic factors in disease-free and overall survivals. These data showed that HE4 expression is associated with a worse prognosis and is a possible prognostic factor of lung adenocarcinoma.