Histochemical and immunohistochemical evidence of tumor heterogeneity in colorectal cancer

Rom J Morphol Embryol. 2015;56(1):175-81.

Abstract

Introduction: Intratumoral heterogeneity implies the existence of differences between tumor cells, which can best be shown by histochemical and immunohistochemical techniques. The histological study is a mandatory step in any research aimed at characterizing tumor heterogeneity. Immunohistochemistry (IHC) also plays an important role in the differentiation of tumor types, assessing aggressiveness.

Materials and methods: Investigated group consisted of 50 patients with colorectal adenocarcinoma, for each were recorded clinicopathological data and harvested samples intraoperatively, which were included in paraffin blocks. We perform Hematoxylin-Eosin staining for histological grade and other indices. IHC study used Avidin-Biotin-Peroxidase (ABC), with the markers: CK7, CK20, MUC1, MUC2, Ki-67, PCNA, p53, KRAS, BCL2, PTEN, EGFR. The resulting data were analyzed by statistical methods.

Results: Most of colorectal adenocarcinoma studied had no special histological features and had G2 grade. IHC detected in most cases the CK20+÷CK7- phenotype (78%) and MUC1 (74%) protein expression. The proliferation markers (Ki-67 and PCNA) were present in all tumor mass with a variable index, which shows high intratumoral heterogeneity, but p53 and KRAS were distributed more uniformly, showing low intratumoral heterogeneity. PTEN was expressed nuclearly in 86% of the cases and EGFR in 42%.

Conclusions: The expression profiles of cytokeratins and mucins in the colorectal adenocarcinomas are useful in defining tumor phenotypes with different prognosis and therapy. We found a significant positive correlation between KRAS protein expression and BCL2 and TP53 expression. The study demonstrated the intratumoral and intertumoral heterogeneity, expressed at phenotypic level.

MeSH terms

  • Adenocarcinoma / metabolism
  • Adenocarcinoma / pathology*
  • Adenocarcinoma, Mucinous / metabolism
  • Adenocarcinoma, Mucinous / pathology
  • Adult
  • Aged
  • Biomarkers, Tumor / metabolism*
  • Colorectal Neoplasms / metabolism
  • Colorectal Neoplasms / pathology*
  • Female
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Immunohistochemistry
  • Keratin-20 / metabolism
  • Ki-67 Antigen / metabolism
  • Male
  • Middle Aged
  • Mucins / metabolism
  • PTEN Phosphohydrolase / metabolism
  • Phenotype
  • Proliferating Cell Nuclear Antigen / metabolism
  • Signal Transduction
  • Tumor Suppressor Protein p53 / metabolism

Substances

  • Biomarkers, Tumor
  • KRT20 protein, human
  • Keratin-20
  • Ki-67 Antigen
  • Mucins
  • Proliferating Cell Nuclear Antigen
  • TP53 protein, human
  • Tumor Suppressor Protein p53
  • PTEN Phosphohydrolase
  • PTEN protein, human