Comprehensive evaluation of serum HE4 and CA125 with HE4 immunohistochemistry for ovarian tumor diagnosis

Abstract

Ovarian tumors present a critical health challenge due to high mortality. Current diagnostic modality like Cancer antigen 125 (CA125) in terms of low sensitivity or ultrasound in terms of cost and expertise have its own limitations. There is a crucial need for novel biomarkers such as Human epididymis protein 4(HE4) which may address their limitations. This study aimed to evaluate the magnitude of immunohistochemical expression of HE4 and correlate it with serum HE4 and CA125 levels in ovarian neoplasm further aiding in diagnosis and prognosis prediction.
Methods and Materials: A cross-sectional study, included 81 patients. Pre- and post-operative serum HE4, CA125 and immunohistochemistry were evaluated.
Results: Out of 81, 40(49.38%) were benign, 4 (4.93%) borderlines and 37(45.67%) malignant. In those benign tumors, 39(97.5%) cases showed S.HE4 level < 140 pmol/L whereas only 17 (42.5%) cases showed CA125 <35U/ml preoperatively. This shows that about 23cases (57.5%) of CA125 positive benign cases emerged as HE4 negative. Elevated preoperative CA125 levels in 59 patients (72.8%) demonstrated variable values in malignant, borderline and benign tumors, highlighting its complexity. Elevated preoperative HE4 levels were observed in 24 patients (92.3%) in malignant ovarian tumors. Combining serum HE4 and CA125 improved sensitivity (88%), specificity (91.56%), and accuracy (82.33%). Immunohistochemistry revealed strong HE4 tissue expression in 18 out of 22 cases (81.8%) of high grade serous and endometrioid carcinoma showing significant correlation with malignancy status.
Conclusions: HE4 emerges as a promising biomarker, both at tissue and serum levels ascribing its specificity to distinguish benign from malignant cases. The combined evaluation of serum HE4 and CA125 levels with immunohistochemical overexpression of HE4 at tissue enhances screening, diagnostic accuracy and prognostic outcomes in patients with ovarian tumors. This approach vouches for improving patient care and outcomes in the management of ovarian cancer.