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SHORT REPORT SCCA antigen combined with alpha-fetoprotein as serologic markers of HCC Gianluigi Giannelli1*, Felice Marinosci1, Paolo Trerotoli2, Anna Volpe3, Michele Quaranta4, Pietro Dentico,3 and Salvatore Antonaci1 1Department of Internal Medicine, Immunology and Infectious Diseases, Section of Internal Medicine, University of Bari, Bari, Italy 2Department of Internal Medicine and Public Health, Section of Medical Statistics, University of Bari Medical School, Bari, Italy 3Department of Internal Medicine, Immunology and Infectious Diseases, Section of Infectious Diseases, University of Bari, Bari, Italy 4Department of Experimental Oncology, Laboratory of Analyses, Institute of Oncology, Bari, Italy Hepatocellular carcinoma (HCC) is the fi fth most common cancer in the world. Because of its increased incidence in the last decade and the estimated further increase in the next 2 decades, HCC is arousing great interest. In Europe and North America, it com- monly develops on cirrhotic livers, and surveillance programs have therefore been suggested to identify early HCC, at a stage when it remains suitable for surgical therapy and has a better clin- ical outcome. The only serologic marker used in clinical practice is a-fetoprotein (a-FP), but its sensitivity is poor. In our study, 120 patients with HCC and 90 patients with liver cirrhosis were inves- tigated. We report for the fi rst time to our knowledge that as a marker of HCC, the squamous cell carcinoma (SCCA) antigen has high sensitivity (84.2%) but low specifi city (48.9%). However, the combination of a-FP and SCCA yielded a correct serologic diag- nosis in 90.83% of the HCC patients. A small percentage of patients remain undetected, likely because of the low specifi city of SCCA. In conclusion, the combined use of a-FP and SCCA anti- gen represents a more powerful tool for the serologic detection of HCC. 2005 Wiley-Liss, Inc. Key words: SCCA; HCC; a-fetoprotein; diagnosis; cirrhosis Hepatocellular carcinoma (HCC) is becoming a major health problem worldwide as it represents the fi fth most common cancer in the world and the third most common cause of cancer-related death. In Europe and the USA, the incidence rates of HCC have strongly increased in the last decade and will likely increase fur- ther in the upcoming 2 decades due to hepatitis C virus infec- tion,1,2although there is some controversy as to whether it is directly responsible for liver cancer development.35In Western and North American countries, HCC commonly develops in cir- rhotic livers whatever the etiology, so that liver cirrhosis by itself represents the strongest risk factor.3,5,6The clinical outcome and the prognosis of HCC are unsatisfactory, even if in developed countries a major improvement of treatment and survival has been achieved in patients with HCC at the initial stage.7Therefore, sur- veillance programs aimed at detecting early stage HCC have been recommended by the European Association for the Study of the Liver (EASL) as well as the Italian Association for the Study of the Liver (AISF). These programs are based on the use of ultra- sound tomography and a-fetoprotein (a-FP). The reliability of imaging techniques has greatly improved in the last years but such diagnostic procedures are expensive and subject to interpretation. On the other hand, as the only diagnostic serologic test currently available in clinical practice, a-FP has too low a sensitivity and specifi city; based on receiving operating characteristic (ROC) curve analysis, its sensitivity reaches only 60%.8 It has been reported that the squamous cell carcinoma antigen (SCCA) is overexpressed in HCC tissues.9SCCA is a component of the high molecular weight serine protease inhibitors named ser- pins.10A different expression of SCCA in HCC and peritumoral tissue has recently been documented, together with a higher con- centration of this antigen in the serum of HCC patients than cir- rhotic patients.11 SCCA is physiologically expressed in the squamous epithelia, and increased levels have been detected in several epithelial can- cers such as those of the head, neck, cervix and lung.12However, no data are yet available on the use of SCCA as a diagnostic test for the detection of HCC. The aim of our study is to investigate whether SCCA serum lev- els represent a useful tool for HCC diagnosis, hence whether SCCA is a better marker than a-FP and fi nally whether, in associa- tion with a-FP, SCCA improves the diagnostic power. Material and methods Patients Serum samples from 120 patients with HCC (95 men and 25 women, aged 4084 years) were included in our study. Sera were stored at 280?C immediately after collection. As reported in Table I, all of the HCC patients were affected by underlying cirrhosis, which was related to HBV in 18/120 (15.0%), to HCV in 87/120 (72.5%), to multiple viral infection in 7/120 (5.83%), to alcohol abuse in 2/120 (1.66%) and to unknown etiology in 6/120 (5.0%) patients. All of the serum s
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