Absence of caspase 3 activation in neoplastic cells of nasopharyngeal carcinoma biopsies predicts rapid fatal outcome

Joost J Oudejans, Ahemd Harijadi, Saskia A G M Cillessen, Pierre Busson, I Bing Tan, Danny F Dukers, Wim Vos, Bambang Hariwiyanto, Jaap Middeldorp, Chris J L M Meijer

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22 Citations (Scopus)


Poor prognosis in nasopharyngeal carcinoma patients may result from resistance to the apoptosis-inducing effect of radio- and/or chemotherapy. Apoptosis depends on proper activation of caspase 3, resulting in cleavage of key proteins like PARP-1. To investigate whether disruption of the apoptosis pathway results in therapy-resistant tumour cells, we investigated whether absence of caspase 3 activation in tumour biopsies of nasopharyngeal carcinoma patients is related to poor clinical outcome. Moreover, we investigated whether absence of caspase 3 activation is related to loss of procaspase 3 expression or expression of the apoptosis regulators p53, bcl-2 and XIAP. We studied 36 Indonesian nasopharyngeal carcinoma patients without evidence of distant metastases who were treated with curative intent by radiotherapy only. Activation of caspase 3 and expression of the different markers were determined using specific antibodies. Levels of caspase 3 activation were determined by quantifying positively staining tumour cells. Nasopharyngeal carcinoma-derived C15 and C17 tumour cells were used as control. Absence of caspase 3 activation was strongly related to a poor clinical response to radiotherapy and to a higher T and N stage, resulting in a particularly poor clinical outcome with regard to progression-free (P<0.0001) and overall survival time (P<0.0001). Absence of caspase 3 activation was significantly correlated to loss of expression of procaspase 3 (P=0.04). In nasopharyngeal carcinoma patients treated with curative intent, absence of active caspase 3-positive neoplastic cells predicts rapid fatal outcome, and is associated with poor response to radiotherapy and high T and N stage at time of presentation.

Original languageEnglish
Pages (from-to)877-885
Number of pages9
JournalModern Pathology
Issue number7
Publication statusPublished - Jul 2005


  • Antineoplastic Agents, Phytogenic
  • Apoptosis
  • Biopsy
  • Caspase 3
  • Caspases
  • Cell Line, Tumor
  • Enzyme Activation
  • Etoposide
  • Female
  • Humans
  • Immunohistochemistry
  • Journal Article
  • Lymphocytes, Tumor-Infiltrating
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Nasopharyngeal Neoplasms
  • Nasopharynx
  • Proteins
  • Proto-Oncogene Proteins c-bcl-2
  • Research Support, Non-U.S. Gov't
  • Survival Analysis
  • Survival Rate
  • T-Lymphocytes, Cytotoxic
  • X-Linked Inhibitor of Apoptosis Protein

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