Ductal invasive G2 and G3 carcinomas of the breast are the end stages of at least two different lines of genetic evolution

Horst Buerger, Ellen C. Mommers, Ruth Littmann, Ronald Simon, Raihanatou Diallo, Christopher Poremba, Barbara Dockhorn-Dworniczak, Paul J. Van Diest, Werner Boecker

Research output: Contribution to journalArticlepeer-review

Abstract

Ductal invasive grade (G) 2 and G3 carcinomas represent the majority of invasive breast cancers. Previous morphological and cytogenetic studies have provided evidence that ductal invasive G2 carcinoma may originate from at least two different genetic pathways. The aim of this study was to evaluate further the heterogeneity of G2 breast cancer in comparison with G3 cancers by cytogenetic and quantitative analysis. To this end, 35 cases of ductal invasive G2 and 42 cases of ductal invasive G3 carcinomas were investigated by means of comparative genomic hybridization (CGH) and these findings were correlated with DNA ploidy status, mitotic activity index (MAI), mean nuclear area (MNA), volume per lumen (VPL), and clinico-pathological parameters. The findings of this study demonstrate that ductal invasive G2 carcinomas, in contrast to ductal invasive G3 carcinomas, have to be interpreted as the morphological end stage resulting from two different' cytogenetic and morphological pathways; the loss of 16q material is the cytogenetic key event in the evolution of a subgroup of this entity. By correlating genetic alterations with DNA ploidy status, an extended morphology-based cytogenetic progression model is presented, with early and late genetic alterations in the pathogenesis of breast cancer. The correlation with MAI gives rise to the hypothesis that these different genetic pathways significantly differ in their proliferation rate. Further studies will be required to elucidate which genes contribute to an altered proliferation rate in these subgroups and to the associated prognosis.

Original languageEnglish (US)
Pages (from-to)165-170
Number of pages6
JournalJournal of Pathology
Volume194
Issue number2
DOIs
StatePublished - 2001
Externally publishedYes

Keywords

  • Breast cancer
  • Carcinogenesis
  • Comparative genomic hybridization

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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