Cerebrospinal Fluid Levels of AFP and hCG: Validation of the Analytical Method and Application in the Diagnosis of Central Nervous System Germ Cell Tumors.

Giada Del Baldo,Annamaria D'Alessandro,Ottavia Porzio,Andrea Onetti Muda,Anna Pastore,Germana Giannone,Angela Mastronuzzi,Domenico Ciavardelli,Andrea Carai

doi:10.3390/diagnostics11111980

Abstract

The determination of Human Chorionic Gonadotropin (hCG) and Alpha Fetoprotein (AFP) levels on serum and amniotic fluid plays a fundamental role in the diagnosis and follow-up of specific physiological or pathological conditions (e.g., pregnancy, threat of abortion or germ cell tumors). Recently, the quantification of hCG and AFP in other biological fluids has gained great attention to support the diagnosis, prognosis and follow-up of neoplastic diseases deriving from trophoblastic cells, such as germinomas. Most of the commercial kits for hCG and AFP assays are developed to be used on biological fluids such as serum/plasma and/or urine by manufacturing companies. The aim of this work was to evaluate the suitability of the analytical method certified for the use on serum, and/or amniotic fluid for the quantification of hCG and AFP in cerebrospinal fluid, carrying out an internal validation protocol. The data reported here show that the automated immunochemical method is fit for quantification of hCG and AFP in cerebrospinal fluid (CSF), allowing selective and specific diagnosis of secreting germ cell tumors. This is confirmed by the positive correlation between elevated levels of hCG or AFP and the diagnosis of brain tumors.

Highlights

The values of the slopes of the recovery functions were found to be significantly different from the ideal value of 1, indicating that quantification of AFP and Human Chorionic Gonadotropin (hCG) in cerebrospinal fluid (CSF) is affected by proportional systematic errors due to the matrix effect
area under the curve (AUC) for hCG was 0.924 and the cut-off hCG concentration of 10.4 mIU/mL provides both sensitivity and specificity of 90% (Figure 3B), indicating that hCG was able to correctly identify the subject not affected by non-germinomatous germ cell tumors (NGGCTs) and has a high positive predictive value
The calculated AUC for hCG was 0.924 and the cut-off hCG concentration of 10.4 mIU/mL. Provides both sensitivity and specificity of 90% (Figure 3B), indicating that hCG was able to correctly identify the subject not affected by NGGCT and has a high positive predictive value

Summary

Introduction

Gonadotropin (hCG) on serum and amniotic fluid plays a fundamental role in the diagnosis, prognosis and follow-up of specific physiological or pathological conditions such as pregnancy, threat of abortion and germ cell tumors (GCTs). There has been great interest in the possibility of determining the values of hCG and AFP in other organic fluids such as cerebrospinal (CSF) [1,2]. Germ cell tumors (GCTs) of the central nervous system (CNS) are classified according to the World Health Organization (WHO) into pure germinomas and non-germinomatous germ cell tumors (NGGCTs) [4]. The presence of specific protein markers produced by germ cell tumors has been extremely important in helping to diagnose GCTs. AFP is detected in endodermal sinus tumors such as yolk sac tumors, and β-HCG is a marker of choriocarcinomas [5]

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