Expression Level of Valosin Containing Protein is Associated with Prognosis of Primary Orbital MALT Lymphoma

  • Zhu, Wen-Wen (Medical College of Qingdao University) ;
  • Kang, Li (Institute of Orbital Disease, General Hospital of Chinese People's Armed Police Forces) ;
  • Gao, Ya-Ping (Beijing Institute of Basic Medical Sciences) ;
  • Hei, Yan (Institute of Orbital Disease, General Hospital of Chinese People's Armed Police Forces) ;
  • Dong, Jie (Beijing Institute of Basic Medical Sciences) ;
  • Liu, Yu (Beijing Institute of Basic Medical Sciences) ;
  • Xiao, Li-Hua (Institute of Orbital Disease, General Hospital of Chinese People's Armed Police Forces) ;
  • Yang, Guang (Beijing Institute of Basic Medical Sciences)
  • Published : 2013.11.30


Objective: To investigate whether the expression level of valosin-containing protein (VCP) is correlated with the prognosis of primary orbital mucosa-associated lymphoid tissue (MALT) lymphoma. Methods: VCP expression in 58 samples from primary orbital MALT lymphoma patients was determined by immunohistochemisty using monoclonal antibodies. Correlations between VCP expression level and prognosis were clarified by statistical analysis. Results: It was found that the percentage of VCP positive cells in samples of primary orbital MALT lymphoma ranged from 32% to 95%. The samples were divided into two groups (level 1 and level 2) according to the median value (45%) of the percentage of VCP positive cells. It was found that the expression level of VCP was significantly correlated with recurrence (P=0.003) and tumor size (P=0.008). At the same time, the 5-year disease-free and overall survival rate of patients of level 1 was significantly better than that of level 2 (P=0.001; P=0.032). There was no observed correlation between the expression level of VCP and other clinical features. Conclusion: VCP could be a useful marker for predicting the prognosis of primary orbital MALT lymphoma.


MALT lymphoma;orbit;VCP;recurrence;survival


  1. Asai T, Tomita Y, Nakatsuka S, et al (2002). VCP (p97) regulates NFkappaB signaling pathway, which is important for metastasis of osteosarcoma cell line. Jpn J Cancer Res, 93, 296-304.
  2. Baeuerle PA, Baltimore D (1988). I kappa B: a specific inhibitor of the NF-kappa B transcription factor. Science, 242, 540-6.
  3. Charlotte F, Doghmi K, Cassoux N, et al (2006). Ocular adnexal marginal zone B cell lymphoma: a clinical and pathologic study of 23 cases. Virchows Arch, 448, 506-16.
  4. Coupland SE (2013). Molecular pathology of lymphoma. Eye (Lond), 27, 180-9.
  5. Dai RM, Chen E, Longo DL, Gorbea CM, Li CC (1998). Involvement of valosin-containing protein, an ATPase Co-purified with IkappaBalpha and 26 S proteasome, in ubiquitin-proteasome-mediated degradation of IkappaBalpha. J Biol Chem, 273, 3562-73.
  6. Eckardt AM, Lemound J, Rana M, Gellrich NC (2013). Orbital lymphoma: diagnostic approach and treatment outcome. World J Surg Oncol, 18, 11, 73.
  7. Franco R, Camacho FI, Caleo A, et al (2006). Nuclear bcl10 expression characterizes a group of ocular adnexa MALT lymphomas with shorter failure-free survival. Mod Pathol, 19, 1055-67.
  8. Goda JS, Le LW, Lapperriere NJ, et al (2011). Localized orbital mucosa-associated lymphoma tissue lymphoma managed with primary radiation therapy: efficacy and toxicity. Int J Radiat Oncol Biol Phys, 81, e659-66.
  9. Graue GF, Finger PT, Maher E, et al (2013). Ocular adnexal lymphoma staging and treatment: American Joint Committee on Cancer versus Ann Arbor. Eur J Ophthalmol, 23, 344-55.
  10. Moslehi R, Schymura MJ, Nayak S, Coles FB (2011). Ocular adnexal non-Hodgkin’s lymphoma: a review of epidemiology and risk factors. Expert Rev Ophthalmol, 6, 181-93.
  11. Nola M, Lukenda A, Bollmann M, et al (2004). Outcome and prognostic factors in ocular adnexal lymphoma. Croat Med J, 45, 328-32.
  12. Padhi S, Paul TR, Challa S, et al (2012). Primary extra nodal non Hodgkin lymphoma: a 5 year retrospective analysis. Asian Pac J Cancer Prev, 13, 4889-95.
  13. Raderer M, Streubel B, Woehrer S, et al (2005). High recurrence rate in patients with MALT lymphoma warrants lifelong follow-up. Clin Cancer Res, 11, 3349-52.
  14. Sjo LD, Ralfkiaer E, Prause JU, et al (2008). Increasing incidence of ophthalmic lymphoma in Denmark from 1980 to 2005. Invest Ophthalmol Vis Sci, 49, 3283-8.
  15. Sjo LD, Heegaard S, Prause JU, et al (2009). Extranodal marginal zone lymphoma in the ocular region: clinical, immunophenotypical, and cytogenetical characteristics. Invest Ophthalmol Vis Sci, 50, 516-22.
  16. Smiljanic M, Milosevic R, Antic D, et al (2013). Orbital and ocular adnexal Mucosa-Associated Lymphoid Tissue (MALT) lymphomas: a single-center 10-year experience. Med Oncol, 30, 722.
  17. Vollmer L (2013). The diagnosis and management of ocular lymphoma. Optom Vis Sci, 90, e56-62.
  18. Wenzel C, Dieckmann K, Fiebiger W, et al (2001). CD5 expression in a lymphoma of the mucosa-associated lymphoid tissue (MALT)-type as a marker for early dissemination and aggressive clinical behaviour. Leuk Lymphoma, 42, 823-9.
  19. Yamamoto S, Tomita Y, Hoshida Y, et al (2003). Expression level of valosin-containing protein is strongly associated with progression and prognosis of gastric carcinoma. J Clin Oncol, 21, 2537-44.
  20. Yamamoto S, Tomita Y, Hoshida Y, et al (2004). Expression of valosin-containing protein in colorectal carcinomas as a predictor for disease recurrence and prognosis. Clin Cancer Res, 10, 651-7.
  21. Yamamoto S, Tomita Y, Nakamori S, et al (2003). Elevated expression of valosin-containing protein (p97) in hepatocellular carcinoma is correlated with increased incidence of tumor recurrence. J Clin Oncol , 21, 447-52.

Cited by

  1. High expression of valosin-containing protein predicts poor prognosis in patients with breast carcinoma vol.36, pp.12, 2015,
  2. In vitro efficacy of a first-generation valosin-containing protein inhibitor (CB-5083) against canine lymphoma vol.16, pp.3, 2018,
  3. Pharmacological targeting of valosin containing protein (VCP) induces DNA damage and selectively kills canine lymphoma cells vol.15, pp.1, 2015,