본문 바로가기
KERD
논문KCI 등재

Prognostic Relevance of the Expression of CA IX, GLUT-1, and VEGF in Ovarian Epithelial Cancers

2

조회

0

다운로드

0

인용

0

참고문헌

키워드

주제분류병리학

초록

Background: Tumor hypoxia is associated with malignant progression and treatment resistance. Hypoxia-related factors, such as carbonic anhydrase IX (CA IX), glucose transporter-1 (GLUT-1), and vascular endothelial growth factor (VEGF) permit tumor cell adaptation to hypoxia. We attempted to elucidate the correlation of these markers with variable clinicopathological factors and overall prognosis. Methods: Immunohistochemistry for CA IX, GLUT-1, and VEGF was performed on formalin-fixed, paraffin-embedded tissues from 125 cases of ovarian epithelial cancer (OEC). Results: CA IX expression was significantly associated with an endometrioid and mucinous histology,nuclear grade, tumor necrosis, and mitosis. GLUT-1 expression was associated with tumor necrosis and mitosis. VEGF expression was correlated only with disease recurrence. Expression of each marker was not significant in terms of overall survival in OECs; however, there was a significant correlation between poor overall survival rate and high coexpression of these markers. Conclusions: The present study suggests that it is questionable whether CA IX, GLUT-1, or VEGF can be used alone as independent prognostic factors in OECs. Using at least two markers helps to predict patient outcomes in total OECs. Moreover, the inhibition of two target gene combinations might prove to be a novel anticancer therapy.

Abstract

Background: Tumor hypoxia is associated with malignant progression and treatment resistance. Hypoxia-related factors, such as carbonic anhydrase IX (CA IX), glucose transporter-1 (GLUT-1), and vascular endothelial growth factor (VEGF) permit tumor cell adaptation to hypoxia. We attempted to elucidate the correlation of these markers with variable clinicopathological factors and overall prognosis. Methods: Immunohistochemistry for CA IX, GLUT-1, and VEGF was performed on formalin-fixed, paraffin-embedded tissues from 125 cases of ovarian epithelial cancer (OEC). Results: CA IX expression was significantly associated with an endometrioid and mucinous histology,nuclear grade, tumor necrosis, and mitosis. GLUT-1 expression was associated with tumor necrosis and mitosis. VEGF expression was correlated only with disease recurrence. Expression of each marker was not significant in terms of overall survival in OECs; however, there was a significant correlation between poor overall survival rate and high coexpression of these markers. Conclusions: The present study suggests that it is questionable whether CA IX, GLUT-1, or VEGF can be used alone as independent prognostic factors in OECs. Using at least two markers helps to predict patient outcomes in total OECs. Moreover, the inhibition of two target gene combinations might prove to be a novel anticancer therapy.

참고문헌 (28)

  1. Siegel R, "Cancer statistics, 2011: the impact of eliminating socioeconomic and racial disparities on premature cancer deaths", CA Cancer J Clin, 61, pp.212~236 (2011)
  2. 정규원, "Cancer Statistics in Korea: Incidence, Mortality, Survival, and Prevalence in 2008", Cancer Research and Treatment, 43(1), pp.1~11 (2011), 대한암학회
  3. Murdoch WJ, "Roles of the ovarian surface epithelium in ovulation and carcinogenesis", Reproduction, 123, pp.743~750 (2002)
  4. Le QT, "Hypoxic gene expression and metastasis", Cancer Metastasis Rev, 23, pp.293~310 (2004)
  5. Ruan K, "Role of hypoxia in the hallmarks of human cancer", J Cell Biochem, 107, pp.1053~1062 (2009)
  6. Harrison L, "Hypoxia and anemia: factors in decreased sensitivity to radiation therapy and chemotherapy?", Oncologist, 9(Suppl 5), pp.31~40 (2004)
  7. Kaluz S, "Transcriptional control of the tumor- and hypoxia-marker carbonic anhydrase 9: a one transcription factor (HIF-1) show?", Biochim Biophys Acta, 1795, pp.162~172 (2009)
  8. Behrooz A, "Dual control of glut1 glucose transporter gene expression by hypoxia and by inhibition of oxidative phosphorylation", J Biol Chem, 272, pp.5555~5562 (1997)
  9. Kim JW, "Effects of hypoxia on tumor metabolism", Cancer Metastasis Rev, 26, pp.291~298 (2007)
  10. Greijer AE, "Up-regulation of gene expression by hypoxia is mediated predominantly by hypoxia-inducible factor 1 (HIF-1)", J Pathol, 206, pp.291~304 (2005)
  11. Semenza GL, "HIF-1: mediator of physiological and pathophysiological responses to hypoxia", J Appl Physiol, 88, pp.1474~1480 (2000)
  12. Ivanov S, "Expression of hypoxia-inducible cell-surface transmembrane carbonic anhydrases in human cancer", Am J Pathol, 158, pp.905~919 (2001)
  13. Giatromanolaki A, "Expression of hypoxia-inducible carbonic anhydrase-9 relates to angiogenic pathways and independently to poor outcome in non-small cell lung cancer", Cancer Res, 61, pp.7992~7998 (2001)
  14. Loncaster JA, "Carbonic anhydrase (CA IX) expression, a potential new intrinsic marker of hypoxia: correlations with tumor oxygen measurements and prognosis in locally advanced carcinoma of the cervix", Cancer Res, 61, pp.6394~6399 (2001)
  15. Yasuda M, "Expression of hypoxia inducible factor-1alpha (HIF-1alpha) and glucose transporter-1 (GLUT-1) in ovarian adenocarcinomas: difference in hypoxic status depending on histological character", Oncol Rep, 19, pp.111~116 (2008)
  16. Cantuaria G, "GLUT-1 expression in ovarian carcinoma: association with survival and response to chemotherapy", Cancer, 92, pp.1144~1150 (2001)
  17. Ferrara N., "The role of vascular endothelial growth factor in pathological angiogenesis", Breast Cancer Res Treat, 36, pp.127~137 (1995)
  18. Shen GH, "Prognostic significance of vascular endothelial growth factor expression in human ovarian carcinoma", Br J Cancer, 83, pp.196~203 (2000)
  19. Silverberg SG, "Histopathologic grading of ovarian carcinoma: a review and proposal", Int J Gynecol Pathol, 19, pp.7~15 (2000)
  20. Miyazawa M, "Therapeutic strategy targeting the mTOR-HIF-1alpha-VEGF pathway in ovarian clear cell adenocarcinoma", Pathol Int, 59, pp.19~27 (2009)
  21. Giatromanolaki A, "Tumour hypoxia, hypoxia signaling pathways and hypoxia inducible factor expression in human cancer", Anticancer Res, 21, pp.4317~4324 (2001)
  22. Semenza GL, "Hypoxia, clonal selection, and the role of HIF-1 in tumor progression", Crit Rev Biochem Mol Biol, 35, pp.71~103 (2000)
  23. Semenza GL, "A nuclear factor induced by hypoxia via de novo protein synthesis binds to the human erythropoietin gene enhancer at a site required for transcriptional activation", Mol Cell Biol, 12, pp.5447~5454 (1992)
  24. Airley RE, "Hypoxic regulation of glucose transport, anaerobic metabolism and angiogenesis in cancer: novel pathways and targets for anticancer therapeutics", Chemotherapy, 53, pp.233~256 (2007)
  25. Jubb AM, "Expression of vascular endothelial growth factor, hypoxia inducible factor 1alpha, and carbonic anhydrase IX in human tumours", J Clin Pathol, 57, pp.504~512 (2004)
  26. Zhong H, "Overexpression of hypoxia-inducible factor 1alpha in common human cancers and their metastases", Cancer Res, 59, pp.5830~5835 (1999)
  27. Choschzick M, "Overexpression of carbonic anhydrase IX (CAIX) is an independent unfavorable prognostic marker in endometrioid ovarian cancer", Virchows Arch, 459, pp.193~200 (2011)
  28. Duncan TJ, "Vascular endothelial growth factor expression in ovarian cancer: a model for targeted use of novel therapies?", Clin Cancer Res, 14, pp.3030~3035 (2008)

관련 논문AI추천

Expression of Carbonic Anhydrase IX Correlates with Histologic Grade and Metastasis in Osteosarcoma박용구, 박혜림, 서진원, Franco Bertoni, Patrizia Bacchini대한병리학회 · Journal of Pathology and Translational Medicine2010 · 제44권 제4호The Clinicopathological Significance of Tissue Levels of Hypoxia-Inducible Factor-1α and Vascular Endothelial Growth Factor in Gastric CancerJoo Ho Lee, Ki-Nam Shim, Kwon Yoo, Seong-Eun Kim, Sung-Ae Jung거트앤리버 소화기연관학회협의회 · Gut and Liver2009 · 제3권 제2호Relationship between the Endogenous Hypoxic Markers Hypoxia Inducible Factor-1α, Carbonic Anhydrase IX, and Epithelial Mesenchymal Transition Regulator TWIST Expression in Non-small Cell Lung Cancer김영대, 박원영, 신동훈, 이민기, 이정희, 이창훈, 정성묵대한병리학회 · Journal of Pathology and Translational Medicine2010 · 제44권 제5호The Role of TWIST in Ovarian Epithelial Cancers김경빈, 김기형, 김지연, 박은영, 서동수, 설미영, 신동훈, 윤만수, 이정희, 최경운대한병리학회 · Journal of Pathology and Translational Medicine2014 · 제48권 제4호DNA Hypomethylation-Mediated Overexpression of Carbonic Anhydrase 9 Induces an Aggressive Phenotype in Ovarian Cancer Cells주웅, 성혜윤, 안정혁연세대학교의과대학 · Yonsei Medical Journal2014 · 제55권 제6호The Potential Roles of MELF-Pattern, Microvessel Density, and VEGF Expression in Survival of Patients with Endometrioid Endometrial Carcinoma: A Morphometrical and Immunohistochemical Analysis of 100 CasesDaniil Rudolfovich Petrenyov, Dmitry Aleksandrovich Zinovkin, Eldar Arkadievich Nadyrov, Md Zahidul Islam Pranjol, Oleg Gennadievich Savchenko대한병리학회 · Journal of Pathology and Translational Medicine2017 · 제51권 제5호

이 간행물의 다른 논문 (15건)