Serum level of HE4 is closely associated with pulmonary adenocarcinoma progression

Abstract

The human epididymis 4 (HE4) protein is expressed in the epididymis and respiratory tract. We previously reported that HE4 is also expressed in pulmonary adenocarcinoma. The purpose of this study was to investigate serum levels of HE4 as a biological marker in pulmonary adenocarcinoma. As the trained set, 102 patients with pulmonary adenocarcinoma who underwent surgery in our institute from 2008 to 2011 were evaluated. They were compared with 58 healthy controls and 16 cases of benign lung disease. In the validation, we used 104 patients with pulmonary adenocarcinoma operated on between 2000 and 2007. Postoperative changes of serum HE4 levels were investigated in 35 patients. The level of HE4 was determined by enzyme immunometric assay and compared with clinicopathological factors. In the trained set, HE4 levels in sera in pulmonary adenocarcinoma were significantly higher than in healthy controls and benign lung disease. Receiver operating characteristic curve showed that HE4 was a good discriminator of pulmonary adenocarcinoma (cut-off point, 50.3 pM; area under curve, 0.825; 95 % confidence interval, 0.76-0.89, p < 0.001). In the validation set, serum HE4 levels were significantly correlated with age, nodal status, and carcinoembryonic antigen. Furthermore, postoperative increase of HE4 serum levels showed a significant correlation with recurrence (p = 0.032). The 5-year overall survival rate was 52.6 % in the HE4-positive group compared with 97.1 % in the HE4-negative group (p = 0.001). These data showed that HE4 expression in sera is associated with progression of pulmonary adenocarcinoma and a possible biomarker.

Human epididymis protein 4 (HE4) in laboratory medicine and an algorithm in renal disorders

“…Besides abnormal HE4 immunoreactivity in pulmonary adenocarcinoma and squamous cell carcinoma [20] with the overexpression of WFDC2 gene [47], different splice variants of HE4 (V1-4) at moderate or high levels were also shown in lung adenocarcinoma cell lines [17] in accordance with a latest study demonstrating a 92.1% positivity of the HE4-V3 variant [49]. Thus, elevated serum HE4 levels were suggested in this malignancy, but only limited data are available in this regard [9,[50][51][52][53]. In our most recent study [53], we also found that HE4 was highly increased in de novo lung cancer in male patients-even without signs and symptoms of the disease-and showed a clear association with tumor size and expansion, but did not differ significantly between histological subtypes of the malignancy similarly to Escudero et al [9].…”

Human epididymis protein 4 may not be a reliable screening biomarker for detecting lung carcinoma patients

“…One of these studies examined a patient's serum prior to chemotherapy and failed to detect any association between HE4 level and histologic subtype among 153 metastatic lung cancer patients (20). Consistent with these studies, we have not observed such a higher cytoplasmic staining among our SCLC cases but HE4 expression among NSCLC cases is consistent with the literature (9,12). We observed HE4 expression in the cytoplasm of bronchial glands next to tumor cells.…”

“…The level of HE4 is significantly elevated in malignant pleural effusions compared to non-malignant effusions (6). Its sensitivity (43.8-69.4%) and specificity (78.5-95.0%) for lung cancer detection (6,7,8) has been previously identified and its increase in the serum after postoperative period was found to correlate with recurrence (9). Its serum concentration is also associated with tumor stage, and disease progression occurred within the first year in patients with small-cell lung cancer (SCLC) (10).…”

Diagnostic Efficiency of HE4 and CYFRA 21-1 in Patients with Lung Cancer.

“…Recently, diagnostic efficiency of HE4 and CYFRA 21-1 in patients with lung cancer has been described in few articles. 4,14,15,[19][20][21][22] Hertlein et al 4 reported significantly higher HE4 values for lung cancer (median: 77.3 pmol/L for female, 89.2 pmol/L for male) compared with healthy controls (40.4 pmol/L for female, 26.2 pmol/L for male). For benign lung diseases, they also indicated median HE4 values as 44.4 pmol/l and 57.1 pmol/L in women and men, respectively.…”