The Diagnostic Value of Serum Squamous Cell Carcinoma Antigen (SCCA) for Prediction of HCC Patients Presented By: Sally Saad Mandour Esawy Ass. Lecturer of Clinical Pathology National Liver Institute, Menoufia University

Introduction

Introduction Hepatocellular Carcinoma (HCC) is the most common type of primary liver cancer which shows a growing incidence worldwide (Vauthey and Brouquet,2013) Each year, hepatocellular carcinoma is diagnosed in more than half a million people (El-Serag, 2011) In Egypt, hepatocellular carcinoma (HCC) is the second most common cancer in men and the 6th most common cancers in women (GLOBOCAN 2008)

Introduction The major clinical risk factor for the development of hepatocellular cancer is cirrhosis of the liver. Chronic infections with the hepatitis B virus (HBV) and the hepatitis C virus (HCV) have been involved in about 80% of cases of HCC worldwide (Marrero and Lok, 2004)

Introduction HCC detected after the onset of symptoms has a dismal prognosis with only (0% – 10%) 5 years survival. In contrast, small HCC detected by surveillance can be curable. As potentially curative treatment modalities are available. Identification of HCC at early stage with a good screening test is, therefore, imperative for favourable outcome (Sarwar et al, 2014).

Introduction Alpha-fetoprotein (AFP) is the major biomarker used for HCC diagnosis, however, its use in the early detection of HCC is limited (Hussein et al, 2008). Serum AFP as a marker for HCC has low sensitivity and high specificity (Sun et al, 2008)

Introduction Squamous cell carcinoma antigen (SCCA), a serine protease inhibitor, is physiologically expressed in the skin and other squamous epithelial cells. SCCA levels were significantly elevated in HCC patients, compared to patients with cirrhosis only or normal subjects (Giannelli et al, 2005).

Aim of the work

Aim of the work This study aimed to evaluate the significance of Squamous cell carcinoma antigen serum level in hepatocellular carcinoma and liver cirrhosis in relation to alpha-feto protein as a conventional marker for HCC, lacking disease sensitivity.

Subjects and methods

Subjects and methods This study was carried out at Clinical Pathology Departments, Faculty of Medicine and National Liver Institute, Menoufia University from June 2012 to November 2013. The study included 30 patients with HCC and 30 patients with liver cirrhosis. In addition to 17 unrelated healthy adult subjects, with matched age and gender, no previous history of liver diseases and negative for HBs Ag and HCV Ab, were included as controls.

Subjects and methods The subjects were classified into 3 groups according to clinical findings, laboratory findings, serological tests and abdominal ultrasound as follows: Group I : This group included 30 patients with cirrhotic liver disease. Group II: This group included 30 patients with HCC. Group III: This group included 17 control subjects with matched age and gender.

Subjects and methods All individuals were subjected to the following: Abdominal ultrasonography. CT scanning. Laboratory investigations including: - Complete blood count. - Kidney functions (serum urea & creatinine) - Liver Profile including total bilirubin (TB), direct bilirubin (DB), Alb, AST, ALT, and prothrombin concentration - Hepatitis viral markers ( HBsAg and HCV Ab) - Serum level of alpha fetoprotein and squamous cell carcinoma antigen by enzyme linked immunosorbent assay.

Results

Results Comparison between levels of Alpha feto- proteins in the studied groups   Group I (cirrhotic) N=30 Group II (HCC) Group III (controls) N=17 Test of significa nce p-value (Mean±SD) AFP >50 μg/L N=19 AFP <50 μg/L N=11 Kruskal Wallis- test AFP (μg/L) 7.41±8.41 25379± 34348 15.7± 17.4 3.27±0.94 48.3 <0.001

Figure (1) the mean values of AFP level reported in studied groups   Figure (1) the mean values of AFP level reported in studied groups

Results Comparison between levels of Squamous cell carcinoma antigen in the studied groups   Group I (cirrhotic) N=30 Group II (HCC) Group III (controls) N=17 Test of significance p-value (Mean±SD) Kruskal Wallis-test SCCA (μg/L) 1.20±1.65 2.0±4.73 1.01±0.35 1.41 0.49

Figure (2) the mean values of SCCA level reported in studied groups   Figure (2) the mean values of SCCA level reported in studied groups

Results Pearson's correlation between Squamous cell carcinoma antigen and other studied parameters   Group I Group II r p-value Age 0.11 0.58 0.14 0.45 Hb (gm/dl) -0.16 0.39 -0.29 0.12 Plt \cmm -0.19 0.29 -0.17 0.36 Pt conc % 0.01 0.95 0.03 0.86 ALT IU/L 0.32 0.08 0.66 AST IU/L 0.37 0.05 0.78

Results Pearson's correlation between Squamous cell carcinoma antigen and other studied parameters   Group I Group II r p-value Total Bilirubin mg\dl -0.15 0.44 -0.08 0.66 Direct Bilirubin mg\dl -0.13 0.51 -0.07 0.70 Alb g/dl -0.31 0.09 -0.12 0.54 Urea mg/dl 0.39 0.03* 0.11 0.55 Creatinine mg/dl 0.42 0.02* 0.19 0.29 AFP μg/L -0.09 0.64

Comparison between AFP & SCCA in HCC group as regarding tumor size Results Comparison between AFP & SCCA in HCC group as regarding tumor size   < 6 cm N=13 > 6 cm N=17 Test of significance p-value (Mean ±SD) Mann Whitney U- test AFP (μg/L) 5279.6±15715.7 24337.7±35424.2 2.70 0.007 SCCA (μg/L) 1.08±1.04 2.71±6.20 0.14 0.89

Results Comparison between AFP & SCCA in HCC group as regarding portal vein thrombosis   Yes N=9 No N=21 Test of significance p-value (Mean ±SD) Mann Whitney U-test AFP (μg/L) 30462.6±37577.6 9914.9±24249.7 2.42 0.02 SCCA (μg/L) 1.11±1.27 2.38±5.59 0.35 0.73

Results Sensitivity, specificity, positive and negative predictive value of alpha fetoprotein and SCCA at cut-off values in cirrhotic and HCC groups.   Area under the curve Cut-off values ng/ml Sensitivity Specificity PPV NPV AFP 0.87 258 60% 100% 71% SCCA 0.56 0.5 73% 44% 57% 62%

Results Sensitivity, specificity, positive and negative predictive value for combination of alpha fetoprotein and SCCA at cut-off values 258 and 0.5 ng /ml respectively:   Sensitivity Specificity PPV NPV Accuracy 100% 47% 65% 0.73%

Results Source of the Curve _____ AFP µg/L _____ SCCA µg/L _____ Reference Line

Conclusion

Conclusion We conclude that despite the slightly high sensitivity of SCCA, AFP remains a relatively good diagnostic marker for HCC with higher specificity than SCCA which lacks accuracy as a diagnostic test for HCC in Egyptians. However combination of the two markers improves their sensitivity as screening tests for hepatocellular carcinoma.

Recommendations

Recommendations More studies on a large scale and larger samples sizes are needed to assess the diagnostic as well as the prognostic value of SCCA in patients with HCC with different etiologies of liver disease not only post viral cirrhosis with inclusion of more hepatitis B patients in the study. Further studies focusing on the quantitative assessment of SCCA in tumor and peritumoral tissues should be correlated with serum studies to improve the discriminatory power of SCCA between HCC patients and controls. We also recommend inclusion of a new group of patients with different cancer etiologies other than HCC for better assessment of SCCA specificity as a tumor marker for hepatocellular carcinoma