Loss of p21 expression is associated with p53 mutations and increased cell proliferation and p27 expression is associated with apoptosis in maxillary sinus squamous cell carcinoma

Acta Otolaryngol. 2005 Jul;125(7):779-85. doi: 10.1080/00016480410023056.

Abstract

Conclusions: Loss of p21 expression dependent on the p53 mutation may be associated with higher tumor cell proliferation, and low p27 expression may be associated with decreased spontaneous apoptosis, resulting in poorer prognosis in patients with maxillary sinus squamous cell carcinoma (SCC).

Objective: We have previously reported that p53 mutations and decreased spontaneous apoptosis were associated with poor prognosis in maxillary sinus SCC. However, whether p21 and p27 expression and cell proliferation correlate with either p53 status, spontaneous apoptosis or prognosis in maxillary sinus SCC has not been evaluated.

Material and methods: Seventy patients with maxillary sinus SCC were analyzed. Tumor biopsy specimens were examined for p21 and p27 expression using an immunohistological method. The percentage of proliferating cells labeled by anti-Ki-67 mAb was expressed as the Ki-67 index (KI).

Results: Loss of p21 expression correlated with p53 mutations (p=0.0072). The KIs in patients without p21 expression and with p53 mutations were significantly higher than those in patients with p21 expression (p=0.0119) and those without p53 mutations (p=0.0048). Patients with p27 expression showed a significantly higher apoptotic index than those without (p=0.0012). Kaplan-Meier analysis showed that p21 expression was closely associated with prolonged disease-free survival in the group with a normal p53 status (p=0.0472). Multivariate analysis identified high KI as an independent prognostic marker (p=0.047).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Apoptosis / genetics*
  • Carcinoma, Squamous Cell / genetics*
  • Carcinoma, Squamous Cell / metabolism
  • Carcinoma, Squamous Cell / pathology
  • Cell Proliferation
  • Cohort Studies
  • Cyclin-Dependent Kinase Inhibitor Proteins / genetics*
  • Cyclin-Dependent Kinase Inhibitor Proteins / metabolism
  • Cyclin-Dependent Kinase Inhibitor p21 / genetics
  • Cyclin-Dependent Kinase Inhibitor p21 / metabolism
  • Cyclin-Dependent Kinase Inhibitor p27 / genetics
  • Cyclin-Dependent Kinase Inhibitor p27 / metabolism
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Immunohistochemistry
  • Ki-67 Antigen / analysis
  • Ki-67 Antigen / metabolism
  • Male
  • Maxillary Sinus Neoplasms / genetics*
  • Maxillary Sinus Neoplasms / metabolism
  • Maxillary Sinus Neoplasms / pathology
  • Middle Aged
  • Mutation*
  • Prognosis
  • Tumor Suppressor Protein p53 / genetics*

Substances

  • CDKN1A protein, human
  • Cyclin-Dependent Kinase Inhibitor Proteins
  • Cyclin-Dependent Kinase Inhibitor p21
  • Ki-67 Antigen
  • Tumor Suppressor Protein p53
  • Cyclin-Dependent Kinase Inhibitor p27