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  3. 21. Serum Levels of Human Epididymis Protein 4 and Cancer Antigen 125 in Different Histological Types of Ovarian Cancer
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21. Serum Levels of Human Epididymis Protein 4 and Cancer Antigen 125 in Different Histological Types of Ovarian Cancer

Sonia Aziz1, Ejaz Hassan Khan2 and Mohsin Shaffi3

ABSTRACT

Objective: To determine level of HE4 and CA125 in patients of ovarian cancer, to determine diagnostic accuracy of HE4 alone and in combination with CA125 for ovarian carcinoma against histopathology report as the gold standard and compare the serum levels of HE4 and CA125 in different histological types of the tumor.

Study Design: Descriptive study.

Place and Duration of Study: This study was conducted at the Armed forces Institute of Pathology (AFIP), Rawalpindi in collaboration with North West School Of Medicine, Peshawar. Duration was one year from March 2015 to March 2016.

Materials and Methods: In this study a total of one hundred and twenty seven women (patients n=87, controls n=40), age greater than 18 years were enrolled.  Women with suspected ovarian malignancy admitted in gynecology ward of North West School of Medicine, were included after written informed consent. Pregnant women, one receiving treatment of ovarian malignancy and those unable to give informed consent were not eligible. All patients underwent imaging by pelvic/abdominal ultrasound to document their presence of ovarian mass. Clinical information was retrieved from the patient’s hospital notes. All patients were diagnosed preoperatively in laparoscopy/laparatomy and confirmed by histopathological evaluation. Ovarian cancer subjects were histologically typed according to WHO classification 2003 by specialized histo pathologists.

Results: Total number of patients were 127.Out of which 87 patients had ovarian cancer while 40 had benign disorders. The mean age of patients with benign tumors was 40 which were significantly lower than those with malignant tumors ( 58 years old, respectively, p < .001). The median range of CA125,   14 (12 -4140) and He4,  913 (58 – 2612) tumor markers were significantly elevated ( P <.001) in ovarian cancer group  compared to benign group i.e CA125 14 (4-241) and HE4 60 (37-151). From Receiver operator characteristic curve analysis, the area under the curve (AUC) was higher for HE4 at 0.934 (95% CI = 0.875 to 0.970) compared to CA125 0.904 (95% CI = 0.839 to 0.949). Serum HE4 at cut off value of 80pmol/L had higher sensitivity (90 percent) and specificity (64 percent) for ovarian cancer, compared to serum CA 125 at cut off value of 53.7U/m L, sensitivity 86% and specificity 59%. The combination of HE4 and CA125 gave the highest sensitivity 96% and specificity 97% respectively for detecting ovarian carcinoma than either marker alone. The bulk of the ovarian cancers (81/87 % or 93% were of the epithelial variety with the serous subtype predominant (76.5%). It is the serous subtye of epithelial ovarian cancer (EOC) that were often biomarker positive (87.1%) compared to other subtypes (mucinous, clear cell and endometroid). The few non-EOC cancers (n=6) were also biomarker positive.

Conclusion: HE4 had higher sensitivity and specificity for detecting ovarian carcinoma in women with pelvic mass compared to CA125. Dual marker combination of HE4 and CA125 was superior to either marker alone in predicting ovarian malignancy. Differential expression of biomarkers was noted among the various EOC varieties of ovarian cancer; serous EOC were more likely to be biomarker positive.

Key Words: Cancer Antigen (CA 125), Human Epididymis Protein 4 (HE4).Epithelial Ovarian Cancer (EOC)

Citation of articles: Aziz S, Khan EH, Shaffi M. Serum levels of Human Epididymis Protein 4 and Cancer Antigen125 in Different Histological Types of Ovarian Cancer. Med Forum 2018;29(6):88-92.