Inducible nitric oxide synthase expression in gastric adenocarcinoma: Impact on lymphangiogenesis and lymphatic metastasis

被引:0
作者
Karadayi N. [1 ]
Kandemir N.O. [2 ]
Yavuzer D. [1 ]
Korkmaz T. [3 ]
Gecmen G. [1 ]
Kokturk F. [4 ]
机构
[1] Department of Pathology, Dr. Lutfi Kirdar Training and Research Hospital, Istanbul
[2] Department of Pathology, Faculty of Medicine, Bulent Ecevit University, Zonguldak
[3] Department of Medical Oncology, Dr. Lutfi Kirdar Training and Research Hospital, Istanbul
[4] Department of Biostatistics, Faculty of Medicine, Bulent Ecevit University, Zonguldak
关键词
Gastric carcinoma; Inducible nitric oxide synthases; Lymph node metastasis; Lymphangiogenesis;
D O I
10.1186/1746-1596-8-151
中图分类号
学科分类号
摘要
Background: Lymphatic metastasis is the most important parameter in the spread of gastric carcinomas. Nitric oxide (NO) is a signaling molecule that plays an important role in inflammation and carcinogenesis. In this study, the possible link between inducible nitric oxide synthase (iNOS) expression with lymphangiogenesis and the clinicopathological parameters of gastric carcinomas was investigated.Methods: In this study, iNOS expression and D2-40 (lymphatic endothelium-specific marker monoclonal antibody) reactivity were examined immunohistochemically in 41 gastric adenocarcinoma and 20 non-neoplastic gastric tissues. iNOS expression was scored semiquantitatively in the tumor parenchyma and stroma. D2-40-positive lymphatic vessels were used in the determination of lymphatic invasion and intratumoral and peritumoral lymphatic vascular density.Results: iNOS expression was higher in gastric carcinoma tissue compared with non-neoplastic tissue. Particularly, iNOS expression in tumor cells was found to be closely related to lymphangiogenesis and lymphatic metastasis. The density of lymphatic invasion as well as intratumoral and peritumoral lymphatic vascular density were positively correlated with lymph node metastasis.Conclusions: Our results suggest that iNOS-mediated NO formation plays an important role in gastric carcinogenesis, tumor lymphangiogenesis, and the development of lymphatic metastases. Inhibition of the NO pathway may be an alternative treatment of gastric carcinomas. Virtual slides: The virtual slides for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1713572940104388. © 2013 Karadayi{dotless} et al.; licensee BioMed Central Ltd.
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  • [1] Yamaguchi T., Fujimori T., Tomita S., Ichikawa K., Mitomi H., Ohno K., Shida Y., Kato H., Clinical validation of the gastrointestinal NET grading system: Ki67 index criteria of the WHO 2010 classification is appropriate to predict metastasis or recurrence, Diagn Pathol, 22, 8, (2013)
  • [2] Ziche M., Morbidelli L., Molecular regulation of tumour angiogenesis by nitric oxide, Eur Cytokine Netw, 20, 4, pp. 164-170, (2009)
  • [3] Singh S., Gupta A.K., Nitric oxide: role in tumour biology and iNOS/NO-based anticancer therapies, Cancer Chemother Pharmacol, 67, 6, pp. 1211-1224, (2011)
  • [4] Burke A.J., Sullivan F.J., Giles F.J., Glynn S.A., The yin and yang of nitric oxide in cancer progression, Carcinogenesis, 34, 3, pp. 503-512, (2013)
  • [5] Zhang W., He X.J., Ma Y.Y., Wang H.J., Xia Y.J., Zhao Z.S., Ye Z.Y., Tao H.Q., Inducible nitric oxide synthase expression correlates with angiogenesis, lymphangiogenesis, and poor prognosis in gastric cancer patients, Hum Pathol, 42, 9, pp. 1275-1282, (2011)
  • [6] Lahdenranta J., Hagendoorn J., Padera T.P., Hoshida T., Nelson G., Kashiwagi S., Jain R.K., Fukumura D., Endothelial nitric oxide synthase mediates lymphangiogenesis and lymphatic metastasis, Cancer Res, 69, 7, pp. 2801-2808, (2009)
  • [7] Massi D., De Nisi M.C., Franchi A., Mourmouras V., Baroni G., Panelos J., Santucci M., Miracco C., Inducible nitric oxide synthase expression in melanoma: implications in lymphangiogenesis, Mod Pathol, 22, 1, pp. 21-30, (2009)
  • [8] Franchi A., Massi D., Santucci M., Masini E., Rossi Degl'Innocenti D., Magnelli L., Fanti E., Naldini A., Ardinghi C., Carraro F., Gallo O., Inducible nitric oxide synthase activity correlates with lymphangiogenesis and vascular endothelial growth factor-C expression in head and neck squamous cell carcinoma, J Pathol, 208, 3, pp. 439-445, (2006)
  • [9] Rajnakova A., Moochhala S., Goh P.M., Ngoi S., Expression of nitric oxide synthase, cyclooxygenase, and p53 in different stages of human gastric cancer, Cancer Lett, 172, pp. 177-185, (2001)
  • [10] Feng C.W., Wang L.D., Jiao L.H., Liu B., Zheng S., Xie X.J., Expression of p53, inducible nitric oxide synthase and vascular endothelial growth factor in gastric precancerous and cancerous lesions: correlation with clinical features, BMC Cancer, 2, pp. 8-14, (2002)