Minichromosome maintenance protein 7 as prognostic marker of tumor aggressiveness in pituitary adenoma patients

Eur J Endocrinol. 2016 Mar;174(3):307-14. doi: 10.1530/EJE-15-0586. Epub 2015 Nov 30.

Abstract

Background: Ki-67 labeling index (LI) is currently regarded as a useful prognostic marker of pituitary adenoma (PA) clinical behavior, although its relevance as a reliable clinical indicator is far from being universally accepted, since both validations and criticisms are found in the literature. Minichromosome maintenance 7 (MCM7), a cell-cycle regulator protein, has been recently proposed as a marker of tumor aggressiveness in tumors from many sites, including the CNS. Therefore, we evaluated MCM7, in comparison to Ki-67, as a potential marker of clinical outcome in PA.

Design and methods: In this single-institution retrospective study, 97 patients with PA (23 ACTH, 12 GH, 29 PRL, 10 FSH/LH, and 23 non-secreting adenomas) were recruited and the prognostic value of both MCM7 and Ki-67 was evaluated by immunohistochemical techniques. In addition, p53 nuclear expression and mitotic index were also evaluated.

Results: Twenty-six of the 97 PA patients recurred during the follow-up period. Cox's regression analysis showed that high nuclear expression of MCM7 LI, unlike Ki-67 LI, was directly associated with a higher (7.7-fold) risk of recurrence/progression. Kaplan-Meier analysis of recurrence/progression-free survival curves revealed that patients with high MCM7 LI (≥15%) had a shorter recurrence/progression-free survival than those with low MCM7 LI (<15%). Moreover, among patients with invasive tumors, high MCM7 LI identified those with the highest risk of recurrence/progression.

Conclusions: Data from this study suggest that MCM7 is a prognostic marker of clinical outcome in PA patients, more reliable and informative than Ki-67.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ACTH-Secreting Pituitary Adenoma / metabolism
  • ACTH-Secreting Pituitary Adenoma / pathology
  • Adenoma / metabolism*
  • Adenoma / pathology
  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / metabolism*
  • Child
  • Disease-Free Survival
  • Female
  • Follicle Stimulating Hormone / metabolism
  • Growth Hormone-Secreting Pituitary Adenoma / metabolism
  • Growth Hormone-Secreting Pituitary Adenoma / pathology
  • Humans
  • Immunohistochemistry
  • Kaplan-Meier Estimate
  • Ki-67 Antigen / metabolism
  • Luteinizing Hormone / metabolism
  • Male
  • Middle Aged
  • Minichromosome Maintenance Complex Component 7 / metabolism*
  • Neoplasm Recurrence, Local / metabolism*
  • Neoplasm Recurrence, Local / pathology
  • Pituitary Neoplasms / metabolism*
  • Pituitary Neoplasms / pathology
  • Prognosis
  • Prolactinoma / metabolism
  • Prolactinoma / pathology
  • Proportional Hazards Models
  • Retrospective Studies
  • Young Adult

Substances

  • Biomarkers, Tumor
  • Ki-67 Antigen
  • Luteinizing Hormone
  • Follicle Stimulating Hormone
  • MCM7 protein, human
  • Minichromosome Maintenance Complex Component 7