Micro-anatomical variation in cellular proliferation in endometrial adenocarcinoma, and inverse correlation between Ki67 and cytokeratin 7 expression

Histopathology. 2010 Jul;57(1):46-54. doi: 10.1111/j.1365-2559.2010.03588.x. Epub 2010 Jun 14.

Abstract

Aims: To investigate micro-anatomical variations in proliferative activity within uterine endometrioid adenocarcinoma with particular emphasis on tumour areas comprising microcystic, elongated and fragmented ('MELF') glands.

Methods and results: Ki67 immunoreactivity was assessed in 29 low-grade endometrial adenocarcinomas specifically comparing conventional tumour glands and areas exhibiting MELF-type alteration. Furthermore, since Ki67 expression differed between the peripheral and central aspects of larger neoplastic glands, these micro-anatomical compartments were assessed separately using a semiquantitative scoring system. Most MELF-type tumour elements were negative for Ki67 or showed only rare (< 5% cells) positivity. In contrast, peripheral conventional tumour glands showed prominent Ki67 labelling, but this was significantly reduced in central glandular areas. An inverse correlation between Ki67 and cytokeratin (CK) 7 expression was noted in many tumours.

Conclusions: Endometrial adenocarcinomas show micro-anatomical variations in Ki67 expression and this is often inversely correlated with CK7 immunoreactivity. MELF-type tumour elements show minimal proliferative activity, a finding that initially appears unexpected for areas of purported active invasion. However, an inverse correlation between cell division and local invasion has been demonstrated in other malignancies, notably during epithelial-mesenchymal transition, and this may reflect a reversible alteration in cellular activity during neoplastic progression.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / metabolism
  • Carcinoma, Endometrioid / metabolism*
  • Carcinoma, Endometrioid / pathology*
  • Cell Proliferation
  • Endometrial Neoplasms / metabolism*
  • Endometrial Neoplasms / pathology*
  • Epithelium / metabolism
  • Epithelium / pathology
  • Female
  • Humans
  • Immunohistochemistry
  • Keratin-7 / metabolism*
  • Ki-67 Antigen / metabolism*
  • Middle Aged
  • Neoplasm Invasiveness / pathology

Substances

  • Biomarkers, Tumor
  • Keratin-7
  • Ki-67 Antigen