Human Epididymis Protein 4 Reference Intervals in a Multiethnic Asian Women Population

Abstract

<b>Background:</b> Ovarian cancer is ranked as the fifth most common cause of cancer death in women. In Malaysia,it is the fourth most common cancer in females. CA125 has been the tumor marker of choice in ovarian cancer butits diagnostic specificity in early stages is only 50%. Hence, there is a critical need to identify an alternative tumormarker that is capable of detecting detect ovarian cancer at an early stage. HE4 is a new tumor marker proposedfor the early diagnosis of ovarian cancer and disease recurrence. Currently, none of the normal ranges of HE4quoted in the literature are based on data for a multiethnic Asian population. Therefore, the aim of this studywas to determine reference intervals for HE4 in an Asian population presenting in University Malaya MedicalCentre, a tertiary reference hospital. Materials and <br/><b>Methods</b>: 300 healthy women were recruited comprising150 premenopausal and 150 postmenopausal women, aged from 20-76 years. All women were subjected to apelvic ultrasonograph and were confirmed to be free from ovarian pathology on recruitment. Serum HE4 levelswere determined by chemiluminescent microparticle immunoassay (CMIA, Abbott Architect). The referenceintervals were determined following CLSI guidelines (C28-A2) using a non-parametric method. <br/><b>Results</b>: Theupper limits of the 95th percentile reference interval (90%CI) for all the women collectively were 64.6 pmol/L,and 58.4 pmol/L for premenopausal) and 69.0 pmol/L for postmenopausal. The concentration of HE4 was notedto increase with age especially in women who were more than 50 years old. We also noted that our proposedreference limit was lower compared to the level given by manufacturer Abbott Architect HE4 kit insert (58.4vs 70 pmol/L for premenopausal group and 69.0 vs 140 pmol/L in the postmenopausal group). The study alsoshowed a significant difference in HE4 concentrations between ethnic groups (Malays and Indians). The levels ofHE4 in Indians appeared higher than in Malays (p<0.05), while no significant differences were noted between theMalays and Chinese ethnic groups. <br/><b>Conclusions</b>: More data are needed to establish a reference interval that willbetter represent the multiethnic Malaysian population. Probably a larger sampling size of equal representationof the Malay, Chinese, Indians as well as the other native ethnic communities will give us a greater confidenceon whether genetics plays a role in reference interval determination.