Reduced p16 expression correlates with lymphatic invasion in colorectal cancers

Hepatogastroenterology. 2003 Nov-Dec;50(54):1756-60.

Abstract

Background/aims: P16, the tumor suppressor gene, plays a crucial role in the most important regulatory pathway involved in the G1/S transition, but its role in gastrointestinal neoplasia remains unclear.

Methodology: To evaluate the possible p16 role in the development of colonic neoplasms, the authors studied p16 immunohistochemical expression of 84 lesions of colorectal cancers, 6 lesions of hyperplastic polyps, 59 lesions of adenomas and 8 lesions of carcinoma in adenoma. Immunohistochemical staining was processed by streptavidin biotin technique. The degree of expression pattern was classified into four types: absent, scattered, or nested, diffuse. Also, the correlation between immunohistochemical expression pattern and clinicopathological features was evaluated.

Results: Compared with normal colonic mucosa, in which virtually no p16 expression was observed, p16 was overexpressed in hyperplastic polyps (33%:2/6) adenomas (46%:27/59), carcinoma in adenoma (88%:7/8) and in adenocarcinomas (98%:82/84). In colorectal cancers, when divided into positive (diffuse or nested) and negative (absent or scattered) subgroups, the negative group showed a higher ratio of lymphatic infiltration (p = 0.04), a higher ratio of deeper invasion (p < 0.01) and a higher ratio showing histology of mucinous carcinoma or poorly differentiated adenocarcinoma (p < 0.01).

Conclusions: In colorectal cancers, a significant correlation of reduced p16 expression and lymphatic invasion was observed, which suggested and colorectal cancers with reduced p16 expression have more aggressive potential of lymphatic infiltration. Also a significant correlation between the overexpression of p16 and tumor progression was demonstrated.

MeSH terms

  • Adenocarcinoma / genetics*
  • Adenocarcinoma / pathology
  • Adenoma / genetics*
  • Adenoma / pathology
  • Adult
  • Aged
  • Aged, 80 and over
  • Cell Transformation, Neoplastic / genetics*
  • Cell Transformation, Neoplastic / pathology
  • Colon / pathology
  • Colorectal Neoplasms / genetics*
  • Colorectal Neoplasms / pathology
  • Cyclin-Dependent Kinase Inhibitor p16 / analysis
  • Cyclin-Dependent Kinase Inhibitor p16 / genetics*
  • Female
  • Gene Expression Regulation, Neoplastic / genetics
  • Humans
  • Immunoenzyme Techniques
  • Intestinal Mucosa / pathology
  • Lymph Nodes / pathology
  • Lymphatic Metastasis / genetics*
  • Lymphatic Metastasis / pathology
  • Male
  • Middle Aged
  • Neoplasm Invasiveness / genetics*
  • Neoplasm Invasiveness / pathology
  • Neoplasm Staging
  • Rectum / pathology

Substances

  • Cyclin-Dependent Kinase Inhibitor p16