Abstract 4582: Haptoglobin proved to be a novel biomarker for intra-operative triage of epithelial ovarian cancer at early stage
Authors: Liu Lin , Zhao Changqing , Annamalai Loganath , Kothandaraman Narasimhan , Biswas Arijit , Choolani Mahesh 
Published: February 2011

Introduction

Epithelial ovarian cancer (EOC) is the leading cause of gynecological cancer-related deaths worldwide, and the prognosis can be greatly improved if cancer is detected at early stage. Intra-operative suspicion of malignancy for women going for ovarian cystectomy is critical for triage of patients for the most suitable surgical procedures. In this study, we aimed to evaluate the diagnostic accuracy of haptoglobin level in ovarian cyst fluid as a potential biomarker for intra-operative triage of EOC in both local (Singapore) and regional (Indonesia and Vietnam) centers and to explore its possible clinical applications.

Methods

We measured haptoglobin concentration in ovarian cyst fluid samples, that were carefully collected during surgery without spillage, from 116 benign tumors, 24 early stage and 31 late stage cancers in Department of Obstetrics and Gynaecology, National University Hospital in Singapore and 6 regional centers in Southeast Asia from 2004-2009, using an in-house sandwich enzyme-linked immunosorbent assay (ELISA). We also tested the feasibility of using a rapid colorimetric assay which measures haptoglobin in 5 minutes and could be potentially used in the operation theater for intra-operative cancer triage and compared it with ELISA and frozen section results.

Results

Our data indicated that cyst fluid haptoglobin level was significantly elevated in both early and late stage EOCs (6.51±2.2 and 6.00±1.9 mg/ml, respectively) as compared to benign tumors (0.83±0.9 mg/ml, p &lt;0.001). It was also proven to be an independent marker from the gold standard serum CA125 as there was absence of linear correlation between the two proteins in early stage (r=-0.109, p=0.735), late stage EOCs (r=0.216, p=0.299) and cancers of all stages (r=-0.039, p=0.796). It showed significantly superior overall diagnostic accuracy (AUC 0.998, 95% CI 0.995-1.002) over serum CA125 (AUC 0.925, 95% CI 0.874-0.977) and risk of malignancy index (RMI) (AUC 0.914, 95% CI 0.859-0.969) in discriminating between benign and malignant tumors by the receiver operating characteristic (ROC) curve analysis (p&lt;0.05). Using 2.85 mg/ml as the cut-off level, cyst fluid haptoglobin achieved sensitivity of 98.2%% (89.0-99.9%), specificity of 97.4% (92.1-99.3%), positive predictive value (PPV) of 94.7% (84.5-98.6%) and negative predictive value (NPV) of 99.1% (94.5-100%). Haptoglobin measured by rapid colorimetric assay was almost as good as ELISA and both can be used as an alternative to frozen section diagnosis (especially in developing countries where frozen section is not available) or as low-cost triage methods.

Conclusion

Cyst fluid haptoglobin is a reliable maker for intra-operative diagnosis of EOC at early stage not only in local but also in regional sample sets, with high sensitivity for malignant tumors and a low false-positive rate allowing for optimal surgical procedure to be carried out.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4582.