DOI QR코드

DOI QR Code

CD44v3 and VEGF-C Expression and its Relationship with Lymph Node Metastasis in Squamous Cell Carcinomas of the Uterine Cervix

  • Liu, Ye-Qing (Department of Pathology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University) ;
  • Li, Hai-Feng (Department of Pathology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University) ;
  • Han, Jing-Jing (Department of Pathology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University) ;
  • Tang, Qiong-Lan (Department of Pathology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University) ;
  • Sun, Qing (Department of Pathology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University) ;
  • Huang, Zhi-Quan (Department of Oral and Maxillofacial Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University) ;
  • Li, Hai-Gang (Department of Pathology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University)
  • Published : 2014.06.30

Abstract

Background: To investigate the expression of CD44v3 and vascular endothelial growth factor-C (VEGF-C) and their relationship with lymph node metastasis in squamous cell carcinomas (SCC) of the uterine cervix. Materials and Methods: Expression of CD44v3 and VEGF-C was analyzed in 109 cases of cervical SCC by immunohistochemistry (IHC). The relationship was analyzed between expression and the patient age, histological differentiation, formation of tumor emboli in lymphoid vessels, lymph node metastasis, FIGO staging, and TNM classification. Results: Expression rates for both CD44v3 and VEGF-C were 43.1% in cervical SCC. The cells with positive immunohistochemical staining of CD44v3 were distributed mainly around the keratin pearls in well differentiated carcinomas, but distributed diffusely in the moderately and poorly differentiated lesions. VEGF-C was found stained positively in most of the tumor cells. There were differences in expression between normal epithelium and atypical hyperplasia as well as carcinoma. Both CD44v3 and VEGF-C were found to be associated positively with lymph node metastasis and TNM classification (both p=0.000). Neither CD44v3 nor VEGF-C was found to be associated with patient age, histological differentiation, formation of tumor emboli in lymphoid vessels and FIGO staging. CD44v3 was found to be associated with VEGF-C positively (p=0.000). Conclusions: Abnormal expression of CD44v3 and VEGF-C is associated closely with the lymph node metastasis in cervical SCC, and these agents may cooperate in carcinogenesis and development of metastatic lesions.

Keywords

References

  1. Banky B, Raso-Barnett L, Barbai T, et al (2012). Characteristics of CD44 alternative splice pattern in the course of human colorectal adenocarcinoma progression. Mol Cancer, 11, 83. https://doi.org/10.1186/1476-4598-11-83
  2. Branca M, Giorgi C, Santini D, et al (2006). Aberrant expression of VEGF-C is related to grade of cervical intraepithelial neoplasia (CIN) and high risk HPV, but does not predict virus clearance after treatment of CIN or prognosis of cervical cancer. J Clin Pathol, 59, 40-7. https://doi.org/10.1136/jcp.2005.026922
  3. Duan L, Ye L, Zhao G, et al (2012). Serum spleen tyrosine kinase and vascular endothelial growth factor-C levels predict lymph node metastasis of oesophageal squamous cell carcinoma. Eur J Cardiothorac Surg.
  4. Fox S B, Gatter K C, Jackson D G, et al (1993). CD44 and cancer screening. Lancet, 342, 548-9. https://doi.org/10.1016/0140-6736(93)91670-H
  5. Gotley D C, Fawcett J, Walsh M D, et al (1996). Alternatively spliced variants of the cell adhesion molecule CD44 and tumour progression in colorectal cancer. Br J Cancer, 74, 342-51. https://doi.org/10.1038/bjc.1996.364
  6. Gombos Z, Xu X, Chu CS, et al (2005). Peritumoral lymphatic vessel density and vascular endothelial growth factor C expression in early-stage squamous cell carcinoma of the uterine cervix. Clin Cancer Res, 11, 8364-71. https://doi.org/10.1158/1078-0432.CCR-05-1238
  7. Hashimoto I, Kodama J, Seki N, et al (2001). Vascular endothelial growth factor-C expression and its relationship to pelvic lymph node status in invasive cervical cancer. Br J Cancer, 85, 93-7. https://doi.org/10.1054/bjoc.2001.1846
  8. Inoue A, Moriya H, Katada N, et al (2008). Intratumoral lymphangiogenesis of esophageal squamous cell carcinoma and relationship with regulatory factors and prognosis. Pathol Int, 58, 611-9. https://doi.org/10.1111/j.1440-1827.2008.02279.x
  9. Jemal A, Siegel R, Xu J, et al (2010). Cancer statistics. CA Cancer J Clin, 60, 277-300 https://doi.org/10.3322/caac.20073
  10. K L Bennett, D G Jackson, J C Simon, et al (1995). D44 isoforms containing exon V3 are responsible for the presentation of heparin-binding growth factor. J Cell Biol, 128, 687-98. https://doi.org/10.1083/jcb.128.4.687
  11. Kunlabut K, Vaeteewoottacharn K, Wongkham C, et al (2012). Aberrant expression of cd44 in bile duct cancer correlates with poor prognosis. Asian Pac J Cancer Prev, 13, 95-9.
  12. Liu L, Ma X-L, Xiao ZL, et al (2012). Prognostic value of vascular endothlial growth factor expression in resected gastric cancer. Asian Pac J Cancer Prev, 13, 3089-97. https://doi.org/10.7314/APJCP.2012.13.7.3089
  13. Li Yuan, Liu Jinzhong, Zheng Yanli, et al (2009). Expressions of CD44v3 and CD54 in oral premalignant epithelia. J Pract Stomatol, 25, 694-7.
  14. Mathur SP, Mathur RS, Gray EA, et al (2005). Serum vascular endothelial growth factor C (VEGF-C) as a specific biomarker for advanced cervical cancer: Relationship to insulin-like growth factor II (IGF-II), IGF binding protein 3 (IGF-BP3) and VEGF-A. Gynecol Oncol, 98, 467-83. https://doi.org/10.1016/j.ygyno.2005.05.003
  15. Naor D, Wallach-Dayan SB, Zahalka MA, et al (2008). Involvement of CD44, a molecule with a thousand faces, in cancer dissemination. Semin Cancer Biol, 18, 260-7. https://doi.org/10.1016/j.semcancer.2008.03.015
  16. Roye GD, Myers RB, Brown D, et al. CD44 expression in dysplastic epithelium and squamous-cell carcinoma of the esophagus. Int J Cancer, 69, 254-8.
  17. SpeiserP, Wanner C, Tempfer C, et al (1997). CD44 is an independent prognostic factor in early-stage cervical cancer. Int J Cancer, 74, 185-8. https://doi.org/10.1002/(SICI)1097-0215(19970422)74:2<185::AID-IJC8>3.0.CO;2-V
  18. Su JL,Yen CJ, Chen PS, et al (2007). The role of the VEGF-C/VEGFR-3 axis in cancer progression. Br J Cancer, 96, 541-5. https://doi.org/10.1038/sj.bjc.6603487
  19. Schlessinger J, Lax I, Lemmon M (1995). Regulation of growth factor activation by proteoglycans: what is the role of the low affinity receptors? Cell, 83, 357-60. https://doi.org/10.1016/0092-8674(95)90112-4
  20. Tavassoli FA, Devilee P, et al (2003). World health organization classification of tumors. pathology and genetics of tumours of the breast and female genital organs. IARC Press: Lyon.
  21. Tawfik OW, Kramer B, Shideler B, et al (2007). Prognostic significance of CD44, platelet-derived growth factor receptor alpha, and cyclooxygenase 2 expression in renal cell carcinoma. Arch Pathol Lab Med, 131, 261-7.
  22. van der Voort R, Taher T E, Wielenga V J, et al (1999). Heparan sulfate-modified CD44 promotes hepatocyte growth factor/scatter factor-induced signal transduction through the receptor tyrosine kinase c-Met. J Biol Chem, 274, 6499-506. https://doi.org/10.1074/jbc.274.10.6499
  23. Wang SJ, Wreesmann VB, Bourguignon LY (2007). Association of CD44 V3-containing isoforms with tumor cell growth, migration, matrix metalloproteinase expression, and lymph node metastasis in head and neckcancer. Head Neck, 29, 550-8. https://doi.org/10.1002/hed.20544
  24. Xie LX, Zhai TT, Yang LP, et al (2013). Lymphangiog enesis and prognostic significance of vascular endothelial growth factor c in gastro-oesophageal junction adenocarcinoma. Int J Exp Pathol, 94, 39-46. https://doi.org/10.1111/iep.12005
  25. Zhongliang Wang, Yao Chen, Xiaofeng Li, et al (2012). Expression of VEGF-C/VEGFR-3 in human laryngeal squamous cell carcinomas and its significance for lymphatic metastasis. Asian Pac J Cancer Prev, 13, 27-31. https://doi.org/10.7314/APJCP.2012.13.1.027

Cited by

  1. Expression of Vimentin and Ki-67 Proteins in Cervical Squamous Cell Carcinoma and their Relationships with Clinicopathological Features vol.16, pp.10, 2015, https://doi.org/10.7314/APJCP.2015.16.10.4271
  2. Remodeling of angiogenesis and lymphangiogenesis in cervical cancer development vol.10, pp.3, 2016, https://doi.org/10.1134/S1990750816030094