Tumour antigen expression in hepatocellular carcinoma in a low-endemic western area
| Autor: | Marco J. Bruno, Jaap Kwekkeboom, Stefan Sleijfer, Katharina Biermann, R.A. de Man, Wojciech G. Polak, Dave Sprengers, Jan N. M. IJzermans, Qiuwei Pan, S.J.A. Bots, Kostandinos Sideras |
|---|---|
| Přispěvatelé: | Gastroenterology & Hepatology, Surgery, Pathology, Medical Oncology |
| Rok vydání: | 2015 |
| Předmět: |
Cancer Research
Pathology medicine.medical_specialty tumour antigens Glypican 3 Annexin-A2 Antigen SDG 3 - Good Health and Well-being Survivin medicine Carcinoma Molecular Diagnostics neoplasms Midkine Tissue microarray biology MAGE-C2 MAGE-C1 hepatocellular carcinoma vaccination medicine.disease Oncology Hepatocellular carcinoma immunohistochemistry biology.protein Immunohistochemistry Glypican-3 |
| Zdroj: | British Journal of Cancer, 112(12), 1911-1920. Nature Publishing Group British Journal of Cancer |
| ISSN: | 0007-0920 |
| Popis: | Background: Identification of tumour antigens is crucial for the development of vaccination strategies against hepatocellular carcinoma (HCC). Most studies come from eastern-Asia, where hepatitis-B is the main cause of HCC. However, tumour antigen expression is poorly studied in low-endemic, western areas where the aetiology of HCC differs. Methods: We constructed tissue microarrays from resected HCC tissue of 133 patients. Expression of a comprehensive panel of cancer-testis (MAGE-A1, MAGE-A3/4, MAGE-A10, MAGE-C1, MAGE-C2, NY-ESO-1, SSX-2, sperm protein 17), onco-fetal (AFP, Glypican-3) and overexpressed tumour antigens (Annexin-A2, Wilms tumor-1, Survivin, Midkine, MUC-1) was determined by immunohistochemistry. Results: A higher prevalence of MAGE antigens was observed in patients with hepatitis-B. Patients with expression of more tumour antigens in general had better HCC-specific survival (P = 0.022). The four tumour antigens with high expression in HCC and no, or weak, expression in surrounding tumour-free-liver tissue, were Annexin-A2, GPC-3, MAGE-C1 and MAGE-C2, expressed in 90, 39, 17 and 20% of HCCs, respectively. Ninety-five percent of HCCs expressed at least one of these four tumour antigens. Interestingly, GPC-3 was associated with SALL-4 expression (P = 0.001), an oncofetal transcription factor highly expressed in embryonal stem cells. SALL-4 and GPC-3 expression levels were correlated with vascular invasion, poor differentiation and higher AFP levels before surgery. Moreover, patients who co-expressed higher levels of both GPC-3 and SALL-4 had worse HCC-specific survival (P = 0.018). Conclusions: We describe a panel of four tumour antigens with excellent coverage and good tumour specificity in a western area, low-endemic for hepatitis-B. The association between GPC-3 and SALL-4 is a novel finding and suggests that GPC-3 targeting may specifically attack the tumour stem-cell compartment. |
| Databáze: | OpenAIRE |
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