Identification of fatal outcome in a childhood nasopharyngeal carcinoma patient by protein expression profiling

Abstract

Nasopharyngeal carcinoma (NPC) is a rare disease in children with good prognosis and high cure rate. Nevertheless, certain patients have an unfavorable prognosis due to development of refractory NPC that is unresponsive to any therapeutic strategies. The current study studies a case of a 17 years-old female with non-keratinizing NPC type IIb (T2N0M0), who passed away as a consequence of resistance to chemo-, radio- and β-interferon therapy, and to an allogenic stem cell transplantation. In order to identify factors that lead to treatment failure and fatal outcome, immunohistochemical analyses of different tumor biomarkers and hierarchical cluster analysis were performed and compared with those of eight other patients with NPC who experienced complete remission following conventional therapy. Hierarchical cluster analysis of the immunohistochemical results clearly demonstrated that staining for immunological factors (CD4, CD8 and CD56) distinguished this patient from the others. To further investigate a potential role of the immune system, lympho-cytic infiltration was assessed in tumor tissue by evaluation of hematoxylin and eosin-stained tumor sections. Indeed, no tumor infiltrating lymphocytes (TILs) were observed in this NPC case, while 7 out of 8 of the other NPC samples contained variable TIL amounts. The view that immunodeficiency of the patient may be a factor in the fatal outcome of treatment is supported by the fact that this patient with NPC was not positive for Epstein-Barr virus markers and also infected by several other viruses and fungi (herpes simplex virus, human herpes virus 6, Varicella zoster virus, and Candida). In conclusion, the investigation of rare NPC cases with poor prognosis may provide an improved understanding of the molecular mechanisms involved in refractory tumors and identification of novel potential therapeutic targets for NPC in the future.