The prognostic significance of p63 cytoplasmic expression in colorectal cancer. An immunohistochemical study

Saudi Med J. 2019 May;40(5):432-439. doi: 10.15537/smj.2019.5.24162.

Abstract

Objectives: To evaluate p63 expression pattern in Saudi colorectal cancer (CRC) patients and correlate that with clinicopathological parameters and its role in carcinogenesis and prognosis.

Methods: Archival tumor samples were analyzed by immunohistochemistry for p63 expression in 324 consecutive Saudi patients diagnosed with CRC between January 2006 and December 2017 at the Pathology Department of a tertiary care Hospital, Madinah, Saudi Arabia.

Results: P63 over-expression was absent in normal mucosa, while 12.5% cases of adenoma showed its over-expression. In CRC, p63 expression was high in 24.1% of cases. There were no significant correlations between p63 expression and gender, tumor location, tumor size and tumor histologic differentiation. However, high p63 expression revealed a significant correlation with age (p=0.035), tumor type (p=0.004), American Joint Committee on Cancer stage (p=0.046), lymph node metastasis (p=0.006), lymphovascular invasion (p=0.006), distant metastasis (p=0.049), high Ki67 expression (p=0.000) and K-ras expression (p=0.002). The Kaplan-Meier analysis revealed a shorter period of survival with p63 over-expression (p less than 0.001). The Cox-regression model analysis showed that p63 over-expression was an independent prognostic marker in CRC (p=0.000).

Conclusion: P63 expression was increased from normal to adenoma to carcinoma sequence. Moreover, p63 cytoplasmic expression seems to be related to high Ki67 indexing, K-ras expression, advanced tumor stage and poor clinical outcome of CRC. These findings suggest a significant role of cytoplasmic p63 expression in tumor progression and prognosis.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / genetics*
  • Biomarkers, Tumor / metabolism*
  • Colorectal Neoplasms / diagnosis*
  • Colorectal Neoplasms / genetics*
  • Colorectal Neoplasms / mortality
  • Colorectal Neoplasms / pathology
  • Cytoplasm / genetics*
  • Cytoplasm / metabolism*
  • Female
  • Gene Expression*
  • Humans
  • Immunohistochemistry
  • Lymphatic Metastasis
  • Male
  • Middle Aged
  • Neoplasm Invasiveness
  • Prognosis
  • Proportional Hazards Models
  • Retrospective Studies
  • Survival Rate
  • Transcription Factors / genetics*
  • Transcription Factors / metabolism*
  • Tumor Suppressor Proteins / genetics*
  • Tumor Suppressor Proteins / metabolism*
  • Young Adult

Substances

  • Biomarkers, Tumor
  • TP63 protein, human
  • Transcription Factors
  • Tumor Suppressor Proteins