Vol. 75, No. 2, 2008
Issue release date: June 2008
Pathobiology 2008;75:104–111
(DOI:10.1159/000123848)
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Understanding the Molecular Basis of Histologic Grade

Ignatiadis M. · Sotiriou C.
Translational Research Unit, Jules Bordet Institute, Brussels, Belgium
email Corresponding Author


 goto top of outline Key Words

  • Histologic grading
  • Breast cancer
  • Gene expression grade index
  • Gene profiling
  • Proliferation

 goto top of outline Abstract

Histologic grading in breast cancer is based on the evaluation of 3 morphologic features (tubule formation, nuclear pleomorphism and mitotic count), is essentially describing proliferation and differentiation in breast cancer, and is considered an important prognostic factor for this disease. It has been suggested that histologic grade 1 and 3 breast tumors are 2 different diseases that may have distinct molecular origins, pathogenesis and natural history. Different single markers like Ki-67, thymidine labeling index and S phase fraction/flow cytometry have been studied as markers of proliferation, but none of them, with the possible exception of Ki-67, is currently employed routinely in clinical practice. The advent of the powerful microarray technology has enabled scientists to comprehensively study proliferation in breast cancer on a genome-wide scale. A gene expression grade index (GGI) was developed that challenges the existence and clinical relevance of an intermediate grade 2 classification. The GGI could reclassify patients with histologic grade 2 tumors into 2 groups with high versus low risks of recurrence. GGI has also been used to define 2 clinically relevant subgroups in estrogen receptor-positive breast carcinomas. Finally, in the largest meta-analysis of publicly available gene expression and clinical data, 4 stable molecular subgroups of breast cancer have been identified, namely ER–/HER–, HER2+ and ER+/HER2–, which was divided into 2 subgroups (ER+/low proliferation and ER+/high proliferation). In this same meta-analysis, proliferation was shown to be the common driving force responsible for the performance of various breast cancer prognostic signatures.

Copyright © 2008 S. Karger AG, Basel


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 goto top of outline Author Contacts

Christos Sotiriou, MD, PhD
Translational Research Unit, Jules Bordet Institute
121, boulevard de Waterloo
BE–1000 Brussels (Belgium)
Tel. +32 2 541 3428, Fax +32 2 538 0858, E-Mail christos.sotiriou@bordet.be


 goto top of outline Article Information

Published online: June 10, 2008
Number of Print Pages : 8
Number of Figures : 2, Number of Tables : 0, Number of References : 51


 goto top of outline Publication Details

Pathobiology (Pathobiology - Exploring the basis of disease)

Vol. 75, No. 2, Year 2008 (Cover Date: June 2008)

Journal Editor: Borisch B. (Geneva), Yasui W. (Hiroshima)
ISSN: 1015–2008 (Print), eISSN: 1423–0291 (Online)

For additional information: http://www.karger.com/PAT


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