Abstract
Background & Objective:This study examined the potential of human epididymis protein 4 (HE4) as a marker in early diagnosis or as a prognostic factor for breast cancer (BC) patients.Methods:A total of 31 patients diagnosed with BC were enrolled in the study between 2008 and 2018. The mRNA and protein expression levels of HE4 were analyzed by immunohistochemistry (IHC) and real-time polymerase chain reaction (PCR) in the BC tissue and the non-tumoral adjacent tissue. Using ELISA technique, HE4 plasma levels were also measured in 43 BC patients compared to 43 healthy individuals. The correlation between HE4 expression and clinicopathological features was then investigated.Results:An increase in HE4 expression was observed at mRNA and protein levels in the BC group compared to the control group (P<0.01, P<0.0001, respectively). In addition, the relative expression of HE4 mRNA in BC patients showed a significant correlation with the differentiation grade of cancer cells (P<0.001). Plasma levels of HE4 was also associated with grade (P<0.0001), stage, and tumor size in BC patients (for both P<0.01). Patients with metastatic BC (P<0.01), lymphatic invasion, and lymph node involvement (for both P<0.05) showed significantly higher plasma levels of HE4 expression than patients without metastasis.Conclusion:According to our findings, upregulation of HE4 may be related to invasive BC phenotype. Measuring plasma levels of HE4 could be useful as a screening test in early diagnosis of BC.
Highlights
Background & ObjectiveThis study examined the potential of human epididymis protein 4 (HE4) as a marker in early diagnosis or as a prognostic factor for breast cancer (BC) patients
Human epididymis protein 4 (HE4), known as whey-acidic-protein (WAP) four-disulfide core domain protein 2 (WFDC2), was initially cloned as one of four proteins that are strongly expressed in human epididymis [1]
Altered expressions of secretory leukocyte protease inhibitor (SLPI) and elafin have been identified in several carcinomas, and it appears that these aberrations may play a role in tumor formation, stimulation of metastatic potential, and development of malignant behavior in cancer cells, including breast cancer (BC) [12, 13]
Summary
A total of 31 patients diagnosed with BC were enrolled in the study between 2008 and 2018. The mRNA and protein expression levels of HE4 were analyzed by immunohistochemistry (IHC) and real-time polymerase chain reaction (PCR) in the BC tissue and the non-tumoral adjacent tissue. We conducted a preliminary study to examine patients who had undergone surgery for primary BC between 2008 and 2018 at Imam Khomeini Hospital Complex, Vol.. Pathological characteristics of patients such as age, tumor size, metastasis, HR status, HER2 expression, and p53 status were gathered from clinical and histopathological records. The pathological stage was defined based on the eighth edition of the TNM Classification of Malignant Tumors of the Union for International Cancer Control [25]. The differentiation grade of cancer cells was determined by a pathologist in accordance with the fourth edition of the World Health Organization (WHO) breast tumors classification [26]
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