Clinical role of tissue and serum levels of SCCA antigen in hepatocellular carcinoma

Giannelli, Gianluigi; Marinosci, Felice; Sgarra, Concetta; Lupo, L.; Dentico, P; Antonaci, Salvatore

doi:10.1002/ijc.20847

Cited by 56 publications

(55 citation statements)

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“…12 Although it is not yet clear why a squamous epithelial antigen such as SCCA is strongly expressed in HCC and the functions for both a-FP and SCCA remain unknown, we cannot rule out the possibility that biologic characteristics of the malignancy may affect the expression level of such an antigen. 11 In any case, in view of all these data, there is no doubt that improvements in SCCA specificity could yield a powerful and reliable tool for serologic screening and diagnosis of HCC.…”

Section: Discussionmentioning

confidence: 99%

“…10 A different expression of SCCA in HCC and peritumoral tissue has recently been documented, together with a higher concentration of this antigen in the serum of HCC patients than cirrhotic patients. 11 SCCA is physiologically expressed in the squamous epithelia, and increased levels have been detected in several epithelial cancers such as those of the head, neck, cervix and lung. 12 However, no data are yet available on the use of SCCA as a diagnostic test for the detection of HCC.…”

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confidence: 99%

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SCCA antigen combined with alpha‐fetoprotein as serologic markers of HCC

Giannelli

Marinosci

Trerotoli

et al. 2005

Intl Journal of Cancer

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Hepatocellular carcinoma (HCC) is the fifth 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 commonly 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 clinical 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 investigated. We report for the first time to our knowledge that as a marker of HCC, the squamous cell carcinoma (SCCA) antigen has high sensitivity (84.2%) but low specificity (48.9%). However, the combination of a-FP and SCCA yielded a correct serologic diagnosis in 90.83% of the HCC patients. A small percentage of patients remain undetected, likely because of the low specificity of SCCA. In conclusion, the combined use of a-FP and SCCA antigen 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 fifth 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 further in the upcoming 2 decades due to hepatitis C virus infection, 1,2 although there is some controversy as to whether it is directly responsible for liver cancer development. [3][4][5] In Western and North American countries, HCC commonly develops in cirrhotic livers whatever the etiology, so that liver cirrhosis by itself represents the strongest risk factor. 3,5,6 The 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. 7 Therefore, surveillance 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 ultrasound 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 specificity; 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. 9 SCCA is a component of the high molecular weight serine protease inhibitors named serpins. 10 A different expressi...

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

SCCA antigen combined with alpha‐fetoprotein as serologic markers of HCC

Giannelli

Marinosci

Trerotoli

et al. 2005

Intl Journal of Cancer

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“…13 Staining was quantified in each section as the total stained area, calculated as the mean of 10 randomly chosen microscopic fields using appropriate image-analyzer software, as already reported. 17 Cytotoxicity Assays. LY2109761 cytotoxicity was determined by 3 methods: the 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazoliumbromide (MTT) assay, manual counting of viable cells, and propidium iodide staining.…”

Section: Methodsmentioning

confidence: 99%

Blocking transforming growth factor-beta up-regulates E-cadherin and reduces migration and invasion of hepatocellular carcinoma cells

et al. 2008

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Hepatocellular carcinoma (HCC) treatment is challenging because the mechanisms underlying tumor progression are still largely unknown. Transforming growth factor (TGF)-␤1 is considered a crucial molecule in HCC tumorigenesis because increased levels of patients' serum and urine are associated with disease progression. The aim of the present study was to investigate the inhibition of TGF-␤ signaling and its impact on HCC progression. Human HCC cell lines were treated with a TGF-␤ receptor kinase inhibitor (LY2109761) whose selectivity was determined in a kinase assay. Exogenous TGF-␤1 phosphorylates the TGF-␤ receptor, consequently activating Smad-2, whereas the drug selectively blocks this effect and dephosphorylates autocrine p-Smad-2 at concentrations ranging from 0.001 to 0.1 M. A cytotoxic effect documented by 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT), trypan blue, and propidium iodide staining assays was observed at 10 M, whereas the drug inhibits (P < 0.001) the migration of HCC cells on fibronectin, laminin-5, and vitronectin and invasion through Matrigel (P < 0.001) at concentrations up to 0.1 M. LY2109761 up-regulates (P < 0.001) E-cadherin mRNA and protein levels. This increase was localized at the cellular membrane where E-cadherin mediates anchorage that is cell-cell dependent. Consistently, a functional monoclonal antibody that inhibits E-cadherin-dependent cell-cell contact restores the migratory and invasive activity. Finally, nonmetastatic HCC tissues from 7 patients were cultured with TGF-␤1 in the presence or absence of LY2109761. E-cadherin expression was reduced by TGF-␤1 and was significantly (P < 0.0001) increased by LY2109761 treatment, measured by quantitative real-time PCR on microdissected tissues and by immunohistochemistry on serial sections. In 72 patients, E-cadherin tissue expression was more weakly expressed in metastatic than in nonmetastatic HCC (P < 0.0001). Conclusion: LY2109761 blocks migration and invasion of HCC cells by upregulating E-cadherin, suggesting that there could be a mechanistic use for this molecule in clinical trials. (HEPATOLOGY 2008;47:1557-1566 H epatocellular carcinoma (HCC) is a highly malignant cancer that is the third most frequent cause of tumor-related death in the United States and Europe. 1 Current therapeutic options are invasive and aim to physically remove or destroy the tumor mass. However, later recurrence and/or metastatic spread are common and negatively affect survival. The overall prognosis is still unsatisfactory, and little progress has been made in finding new treatment options. However, a recent study with sorafenib suggests that targeting the vasculature may provide additional insights into how to develop future treatment options for patients with HCC. 2 Based on the recent clinical observations with sorafenib, the focus for developing new treatments in HCC has shifted from targeting the cancer to targeting the tissue microenvironment and its role in modulating the biological behavior of HCC. 3 Transforming grow...

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“…Previous researches revealed that IgM-linked immunocomplexes instead of the free isoforms could be detected in serum of chronic liver disease patients [20,21]. However, no correlation was found between serum and tissue levels of SCCA antigen [19], so serum SCCA1, 2 concentrations could not represent the level of SCCA1, 2 expression in HCC tissue and the expression of SCCA1, 2 in HCC tissue remains unknown. The aim of this investigation was to study the pattern of expression of the SCCA1 and SCCA2 in different extent of liver diseases, and to define the clinical and prognostic significance in HCC.…”

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confidence: 96%

“…Recently Pontisso et al [17] detected SCCA expression in HCC by immunohistochemistry for the first time but the expression pattern of SCCA1 and SCCA2 in cancer pathogenesis is not fully defined. Biasiolo et al [18] quantified IgM-linked SCCA1, 2 isoforms in serum of patients with chronic liver diseases, however, their result could not represent the expression of SCCA isoforms in HCC since no correlation was found between serum and tissue levels of SCCA antigen [19]. Furthermore, to date no information is available on the clinical and prognostic significance of SCCA variants.…”

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Squamous cell carcinoma antigen 1 and 2 mRNA and a new variant expressed in hepatocellular carcinoma

LI¹,

Gao²,

Yang³

et al. 2014

neo

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New tools for diagnostic of HCC remain to further investigate. We have evaluated the expression of SCCA1, 2 mRNA and their prognostic value in hepatocellular carcinoma (HCC).Reverse transcription polymerase chain reaction (RT-PCR) and direct sequencing were performed to evaluate the mRNA expression of SCCA1 and SCCA2 in 93 HCCs, and 93 paired adjacent non-cancerous tissues (PNT), 16 cirrhosis livers and 9 normal livers. The correlation of SCCA variants expression with the clinical parameters and the factors affecting survival were analyzed statistically.Total SCCA was detected in 33.3% of HCCs (31/93), in 9.68% of PNT (9/93) and 22.2% of normal livers (2/9). No expression was found in cirrhosis livers (0/16). The frequencies of total SCCA expression were significantly higher in HCCs than that in PNT and liver cirrhosis (p = 0.000, 0.006). From mRNA sequencing of HCCs, a new SCCA1 variant (presenting a T357A mutation) was identified in 16 specimens, while wild type SCCA1 was identified in 11 specimens and SCCA2 in 27 specimens. Clinicopathological analysis showed that the frequency of SCCA1 was significantly higher in poorly differentiated HCC, compared with moderately and well differentiated tumors (p = 0.021). T357A variant has a significantly higher frequency in nonencapsulated tumors than wild type SCCA1 (p = 0.034).The SCCA1, 2 mRNA is effective for detecting HCC and could be potentially applied in HCC diagnosis. Key words: hepatocellular carcinoma, liver diseases, prognosis, squamous cell carcinoma antigenNeoplasma 61, 6, 2014 doi:10.4149/neo_2014_087 Liver cancer is the fifth most frequently diagnosed cancer but the second most frequent cause of cancer death in men worldwide (half of these cases and deaths are estimated to occur in China), and approximately, 70-85% of the total liver cancer are classified as hepatocellular carcinoma (HCC) [1]. Early detection enables us to provide the patients with more therapeutic options, which can improve survival rate of patients and reduce medical costs [2]. Despite the fact that serum AFP is still the golden standard amongst diagnostic markers for HCC, its diagnostic value is more and more questioned, because of its poor sensitivity and specificity [3,4]. Therefore, investigators are seeking for better HCC biomarkers.Squamous cell carcinoma antigen (SCCA), originally isolated from SCC tissue of the uterine cervix, is a member of the family of serine protease inhibitors [5]. The neutral and acidic isoforms of SCCA are encoded by 2 separate, but highly homologous genes, SCCA1 and SCCA2, at chromosome 18q21.3 [6]. Although SCCA1 and SCCA2 are with 91% identity at the amino acid concentration, they have distinct properties and substrate specificities. SCCA1 also known as SERPINB3, a papain-like cysteine proteinase inhibitor, inhibits cathepsins K, L and S [7]. SCCA2 also known as SERPINB4, a chymotrypsin-like serine proteinase inhibitor, inhibits proteolytic activity of endogenous cathepsin G and mast cell chymase [8]. The biological role of this serpin in carcinoge...

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Clinical role of tissue and serum levels of SCCA antigen in hepatocellular carcinoma

Cited by 56 publications

References 14 publications

SCCA antigen combined with alpha‐fetoprotein as serologic markers of HCC

SCCA antigen combined with alpha‐fetoprotein as serologic markers of HCC

Blocking transforming growth factor-beta up-regulates E-cadherin and reduces migration and invasion of hepatocellular carcinoma cells

Squamous cell carcinoma antigen 1 and 2 mRNA and a new variant expressed in hepatocellular carcinoma

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Clinical role of tissue and serum levels of SCCA antigen in hepatocellular carcinoma

Cited by 56 publications

References 14 publications

SCCA antigen combined with alpha‐fetoprotein as serologic markers of HCC

SCCA antigen combined with alpha‐fetoprotein as serologic markers of HCC

Blocking transforming growth factor-beta up-regulates E-cadherin and reduces migration and invasion of hepatocellular carcinoma cells

Squamous cell carcinoma antigen 1 and 2 mRNA and a new variant expressed in hepatocellular carcinoma

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Squamous cell carcinoma antigen 1 and 2 mRNA and a new variant expressed in hepatocellular carcinoma