Correlation of LMP10 expression and clinical outcome in Human Papillomavirus (HPV) positive and HPV-Negative tonsillar and base of tongue cancer

PLoS One. 2014 Apr 21;9(4):e95624. doi: 10.1371/journal.pone.0095624. eCollection 2014.

Abstract

Aim: To examine LMP10 expression and its possible impact on clinical outcome in human papillomavirus (HPV) positive and HPV-negative tonsillar and base of tongue squamous cell carcinoma (TSCC and BOTSCC).

Background: Outcome is better in HPV-positive TSCC and BOTSCC compared to matching HPV-negative tumours, with roughly 80% vs. 40% 5-year disease free survival (DFS) with less aggressive treatment than today's chemoradiotherapy. Since current treatment often results in harmful side effects, less intensive therapy, with sustained patient survival would be an attractive alternative. However, other markers together with HPV status are necessary to select patients and for this purpose LMP10 expression is investigated here in parallel to HPV status and clinical outcome.

Materials and methods: From 385 patients diagnosed between 2000 and 2007 at the Karolinska University Hospital, 278 formalin fixed paraffin embedded TSCC and BOTSCC biopsies, with known HPV DNA status, were tested for LMP10 nuclear and cytoplasmic expression (fraction of positive cells and staining intensity). The data was then correlated to clinical outcome.

Results: An absent/low compared to a moderate/high LMP10 nuclear fraction of positive cells was correlated to a better 3-year DFS in the HPV-positive group of patients (log-rank p = 0.005), but not in the HPV-negative group. In the HPV-negative group of patients, in contrast to the HPV-positive group, moderate/high LMP10 cytoplasmic fraction and weak/moderate/high LMP10 cytoplasmic intensity correlated to a better 3-year DFS (p = 0.003 and p = 0.001) and 3-year overall survival (p = 0.001 and 0.009).

Conclusion: LMP10 nuclear expression in the HPV-positive group and LMP10 cytoplasmic expression in the HPV-negative group of patients correlated to better clinical outcome.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Cell Nucleus / metabolism
  • Disease-Free Survival
  • Female
  • Histocompatibility Antigens Class I / metabolism
  • Humans
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Papillomavirus Infections / metabolism*
  • Papillomavirus Infections / pathology
  • Papillomavirus Infections / virology
  • Proteasome Endopeptidase Complex / metabolism*
  • Staining and Labeling
  • Tongue Neoplasms / metabolism*
  • Tongue Neoplasms / pathology
  • Tongue Neoplasms / virology*
  • Tonsillar Neoplasms / metabolism*
  • Tonsillar Neoplasms / pathology
  • Tonsillar Neoplasms / virology*
  • Treatment Outcome

Substances

  • Histocompatibility Antigens Class I
  • PSMB10 protein, human
  • Proteasome Endopeptidase Complex