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Published in: Diagnostic Pathology 1/2011

Open Access 01-12-2011 | Research

Tissue expression of squamous cellular carcinoma antigen and Ki67 in hepatocellular carcinoma-correlation with prognosis: A historical prospective study

Authors: Hemda Schmilovitz-Weiss, Ana Tobar, Marisa Halpern, Izhar Levy, Esther Shabtai, Ziv Ben-Ari

Published in: Diagnostic Pathology | Issue 1/2011

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Abstract

Background

Squamous cellular carcinoma antigen (SCCA) is overexpressed in hepatocellular carcinoma (HCC) tissue and in sera of HCC patients. Our aim was to assess hepatic SCCA immunostaining in a series of HCCs and to correlate its presence with cell proliferation, apoptosis and clinical outcome.

Methods

Sixty-one HCC patients were included. Liver specimens were obtained either by biopsy (n = 17) or surgically (resection 27, transplantation 17). Immunostaining for AFP, Ki-67, SCCA and TUNEL assay were performed.

Results

SCCA staining was detected in 83.6% of specimens. A statistical significant correlation was found between negative SCCA staining and mortality (p = 0.026) and a higher immunostaining score for Ki67 (p = 0.017). Positive SCCA staining was associated with well and moderate differentiated tumors (p = 0.022). Using multiple logistic regression analysis, Ki67 and TUNEL assay were found to be significant independent predictors of negative SCCA immunostaining. The area under the receiver operator characteristic curve was 0.87. Kaplan-Meier survival analysis revealed a significant difference between the patient group with positive versus negative SCCA immunostaining relating to survival time (p = 0.0106). Cox proportional hazard regression analysis demonstrated that Ki67 immunostaining and liver transplantation or resection were independently associated with mortality.

Conclusions

SCCA is overexpressed in HCC. SCCA status is associated with cell proliferation, apoptosis and survival. SCCA and Ki67 staining can predict survival. Our study results support a potential association of negative SCCA expression with other markers of poor outcome in HCC. More studies are needed to clarify the role of SCCA in HCC and expand the knowledge of the SCCA antigen in HCC patients.
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Literature
1.
go back to reference Llovet JM, Bruix J: Novel advancements in the management of hepatocellular carcinoma in 2008. J Hepatol. 2008, 1: S20-S37.CrossRef Llovet JM, Bruix J: Novel advancements in the management of hepatocellular carcinoma in 2008. J Hepatol. 2008, 1: S20-S37.CrossRef
2.
go back to reference Parkin DM, Bray F, Ferlay J, Pisani P: Global cancer statistics 2002. CA Cancer J Clin. 2005, 55: 74-108. 10.3322/canjclin.55.2.74.CrossRefPubMed Parkin DM, Bray F, Ferlay J, Pisani P: Global cancer statistics 2002. CA Cancer J Clin. 2005, 55: 74-108. 10.3322/canjclin.55.2.74.CrossRefPubMed
3.
go back to reference El Serag HB, Mason AC: Rising incidence of hepatocellular carcinoma in the United States. N Engl J Med. 1999, 340: 745-750. 10.1056/NEJM199903113401001.CrossRefPubMed El Serag HB, Mason AC: Rising incidence of hepatocellular carcinoma in the United States. N Engl J Med. 1999, 340: 745-750. 10.1056/NEJM199903113401001.CrossRefPubMed
4.
go back to reference Sangiovanni A, Del Ninno E, Fasani P, De Fazio C, Ronchi G, Romeo R, Morabito A, De Franchis R, Colombo M: Increased survival of cirrhotic patients with a hepatocellular carcinoma detected during surveillance. Gastroenterology. 2004, 126: 1005-1014. 10.1053/j.gastro.2003.12.049.CrossRefPubMed Sangiovanni A, Del Ninno E, Fasani P, De Fazio C, Ronchi G, Romeo R, Morabito A, De Franchis R, Colombo M: Increased survival of cirrhotic patients with a hepatocellular carcinoma detected during surveillance. Gastroenterology. 2004, 126: 1005-1014. 10.1053/j.gastro.2003.12.049.CrossRefPubMed
5.
go back to reference Sherman M, Peltekian KM, Lee C: Screening for hepatocellular carcinoma in chronic carriers of hepatitis B virus: incidence and prevalence of hepatocellular carcinoma in a North American urban population. Hepatology. 1995, 22: 432-438.PubMed Sherman M, Peltekian KM, Lee C: Screening for hepatocellular carcinoma in chronic carriers of hepatitis B virus: incidence and prevalence of hepatocellular carcinoma in a North American urban population. Hepatology. 1995, 22: 432-438.PubMed
6.
go back to reference Llovet JM, Burroughs A, Bruix J: Hepatocellular carcinoma. Lancet. 2003, 362: 1907-1917. 10.1016/S0140-6736(03)14964-1.CrossRefPubMed Llovet JM, Burroughs A, Bruix J: Hepatocellular carcinoma. Lancet. 2003, 362: 1907-1917. 10.1016/S0140-6736(03)14964-1.CrossRefPubMed
7.
go back to reference Bruix J, Sherman M: Management of hepatocellular carcinoma. Hepatology. 2005, 42: 1208-1236. 10.1002/hep.20933.CrossRefPubMed Bruix J, Sherman M: Management of hepatocellular carcinoma. Hepatology. 2005, 42: 1208-1236. 10.1002/hep.20933.CrossRefPubMed
8.
go back to reference Nakanishi K, Sakamoto M, Yamasaki S, Todo S, Hirohashi S: Akt phosphorylation is a risk factor for early disease recurrence and poor prognosis in hepatocellular carcinoma. Cancer. 2005, 103: 307-312. 10.1002/cncr.20774.CrossRefPubMed Nakanishi K, Sakamoto M, Yamasaki S, Todo S, Hirohashi S: Akt phosphorylation is a risk factor for early disease recurrence and poor prognosis in hepatocellular carcinoma. Cancer. 2005, 103: 307-312. 10.1002/cncr.20774.CrossRefPubMed
9.
go back to reference D'Errico A, Grigioni WF, Fiorentino M, Baccarini P, Grazi GL, Mancini AM: Overexpression of p53 protein and Ki67 proliferative index in hepatocellular carcinoma: an immuno-histochemical study on 109 Italian patients. Pathol Int. 1994, 44: 682-687.CrossRefPubMed D'Errico A, Grigioni WF, Fiorentino M, Baccarini P, Grazi GL, Mancini AM: Overexpression of p53 protein and Ki67 proliferative index in hepatocellular carcinoma: an immuno-histochemical study on 109 Italian patients. Pathol Int. 1994, 44: 682-687.CrossRefPubMed
11.
go back to reference Suminami Y, Kishi F, Sekiguchi K, Kato H: Squamous cell carcinoma antigen is a new member of the serine protease inhibitors. Biochem Biophys Res Commun. 1991, 181: 51-58. 10.1016/S0006-291X(05)81380-4.CrossRefPubMed Suminami Y, Kishi F, Sekiguchi K, Kato H: Squamous cell carcinoma antigen is a new member of the serine protease inhibitors. Biochem Biophys Res Commun. 1991, 181: 51-58. 10.1016/S0006-291X(05)81380-4.CrossRefPubMed
12.
go back to reference Torre GC: SCC antigen in malignant and nonmalignant squamous lesions. Tumour Biol. 1998, 19: 517-526. 10.1159/000030045.CrossRefPubMed Torre GC: SCC antigen in malignant and nonmalignant squamous lesions. Tumour Biol. 1998, 19: 517-526. 10.1159/000030045.CrossRefPubMed
13.
go back to reference Giannelli G, Marinosci F, Sgarra C, Lupo L, Dentico P, Antonaci S: Clinical role of tissue and serum levels of SCCA antigen in hepatocellular carcinoma. Int J Cancer. 2005, 116: 579-583. 10.1002/ijc.20847.CrossRefPubMed Giannelli G, Marinosci F, Sgarra C, Lupo L, Dentico P, Antonaci S: Clinical role of tissue and serum levels of SCCA antigen in hepatocellular carcinoma. Int J Cancer. 2005, 116: 579-583. 10.1002/ijc.20847.CrossRefPubMed
14.
go back to reference Pontisso P, Calabrese F, Benvegnù L, Lise M, Belluco C, Ruvoletto MG, Marino M, Valente M, Nitti D, Gatta A, Fassina G: Overexpression of squamous cell carcinoma antigen variants in hepatocellular carcinoma. Br J Cancer. 2004, 90: 833-837. 10.1038/sj.bjc.6601543.PubMedCentralCrossRefPubMed Pontisso P, Calabrese F, Benvegnù L, Lise M, Belluco C, Ruvoletto MG, Marino M, Valente M, Nitti D, Gatta A, Fassina G: Overexpression of squamous cell carcinoma antigen variants in hepatocellular carcinoma. Br J Cancer. 2004, 90: 833-837. 10.1038/sj.bjc.6601543.PubMedCentralCrossRefPubMed
15.
go back to reference Guido M, Roskams T, Pontisso P, Fassan M, Thung SN, Giacomelli L, Sergio A, Farinati F, Cillo U, Rugge M: Squamous cell carcinoma antigen in human liver carcinogenesis. J Clin Pathol. 2008, 61: 445-447. 10.1136/jcp.2007.051383.CrossRefPubMed Guido M, Roskams T, Pontisso P, Fassan M, Thung SN, Giacomelli L, Sergio A, Farinati F, Cillo U, Rugge M: Squamous cell carcinoma antigen in human liver carcinogenesis. J Clin Pathol. 2008, 61: 445-447. 10.1136/jcp.2007.051383.CrossRefPubMed
16.
go back to reference Suminami Y, Nagashima S, Vujanovic NL, Hirabayashi K, Kato H, Whiteside TL: Inhibition of apoptosis in human tumour cells by the tumour-associated serpin, SCC antigen. Br J Cancer. 2000, 82: 981-989. 10.1054/bjoc.1999.1028.PubMedCentralCrossRefPubMed Suminami Y, Nagashima S, Vujanovic NL, Hirabayashi K, Kato H, Whiteside TL: Inhibition of apoptosis in human tumour cells by the tumour-associated serpin, SCC antigen. Br J Cancer. 2000, 82: 981-989. 10.1054/bjoc.1999.1028.PubMedCentralCrossRefPubMed
17.
go back to reference Kato H: Squamous cell carcinoma antigen. Serological Cancer Markers. Edited by: Sell S. 1992, Totowa: Humana Press, 437-451.CrossRef Kato H: Squamous cell carcinoma antigen. Serological Cancer Markers. Edited by: Sell S. 1992, Totowa: Humana Press, 437-451.CrossRef
18.
go back to reference Watanabe J, Kushihata F, Honda K, Sugita A, Tateishi N, Mominoki K, Matsuda S, Kobayashi N: Prognostic significance of Bcl-xL in human hepatocellular carcinoma. Surgery. 2004, 135: 604-612. 10.1016/j.surg.2003.11.015.CrossRefPubMed Watanabe J, Kushihata F, Honda K, Sugita A, Tateishi N, Mominoki K, Matsuda S, Kobayashi N: Prognostic significance of Bcl-xL in human hepatocellular carcinoma. Surgery. 2004, 135: 604-612. 10.1016/j.surg.2003.11.015.CrossRefPubMed
19.
go back to reference Trerotoli P, Fransvea E, Angelotti U, Trerotoli P, Fransvea E, Angelotti U, Antonaci G, Lupo L, Mazzocca A, Mangia A, Antonaci S, Giannelli G: Tissue expression of squamous cellular carcinoma antigen (SCCA) is inversely correlated to tumor size in HCC. Mol Cancer. 2009, 8: 29-10.1186/1476-4598-8-29.PubMedCentralCrossRefPubMed Trerotoli P, Fransvea E, Angelotti U, Trerotoli P, Fransvea E, Angelotti U, Antonaci G, Lupo L, Mazzocca A, Mangia A, Antonaci S, Giannelli G: Tissue expression of squamous cellular carcinoma antigen (SCCA) is inversely correlated to tumor size in HCC. Mol Cancer. 2009, 8: 29-10.1186/1476-4598-8-29.PubMedCentralCrossRefPubMed
Metadata
Title
Tissue expression of squamous cellular carcinoma antigen and Ki67 in hepatocellular carcinoma-correlation with prognosis: A historical prospective study
Authors
Hemda Schmilovitz-Weiss
Ana Tobar
Marisa Halpern
Izhar Levy
Esther Shabtai
Ziv Ben-Ari
Publication date
01-12-2011
Publisher
BioMed Central
Published in
Diagnostic Pathology / Issue 1/2011
Electronic ISSN: 1746-1596
DOI
https://doi.org/10.1186/1746-1596-6-121

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