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Expression of genes involved in DNA repair and cell cycle checkpoint pathways in Triple Negative compared to Luminal A Breast Cancer: a molecular characterization

  • Monica Ganzinelli
  • Enilze Ribeiro
  • Ramona Bertoni
  • Letizia Bazzola
  • Daniele Andreis
  • Alberto Bottini
  • Roberto Giardini
  • Camillo Rossi
  • Giovanna Damia
  • Daniele Generali
Open Access
Meeting abstract
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Keywords

Breast Cancer Progesterone Receptor Triple Negative Breast Cancer Excision Repair Nucleotide Excision Repair 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Purpose

Considering the clear emerging role of the DNA repair and the cell cycle checkpoints as predictive, prognostic and therapeutic targets in cancer there is a need to better characterized human tumours to define sub-sets of patients that would benefit of a particular treatment modality. The aim of the present work is to characterize molecularly a cohort of Triple Negative Breast Cancers (TNBC; estrogen receptor negative, progesterone receptor negative, and HER2/neu negative by immunohistochemistry) compared to Luminal A Breast Cancer (LABC; estrogen receptor positive and/or progesterone receptor positive, and HER2/neu negative, ki67 expression < 15% by immunohistochemistry) as regard of gene expression involved in DNA repair pathway (in particular genes involved in nucleotide excision repair, base excision repair, homologous recombination repair and BRCA/Fanconi anemia pathway) and cell cycle checkpoint pathway (CHK1) and their correlation with the clinical-pathological characteristics.

Experimental design

A single core from archived clinically annotated tumor specimens from 80 women with TNBC and 70 with LABC were performed using Tissue Micro Array machine. The mRNA expression by RT-PCR of in genes involved in NER pathway (ERCC1, XPA, XPG), in the FA/BRCA pathway (FANC-A, FANC-C, FANC-F, FANC-D2), in BER pathway (PARP) and cell cycle checkpoint (Chk1) were analyzed by RT-PCR. Scores of single genes were combined with clinical data to assess association with outcome (Overall Survival –OS- and Event Free Survival –PFS).

Results

Among the NER genes, ERCC1 (p < 0.0001) and XPA (p = 0.03) genes were significantly less expressed in TNBC than in LABC; among the FA genes, BRCA1 (p < 0.0001), FANCD2 (p < 0.0001), FANCF (p < 0.0001) and PALB2 (p = 0.0006) genes were significantly less expressed in TNBC than in LABC. Also CHK1 was less expressed in TNBC (p < 0.0001).

In relation to the clinical-pathological characteristics, lower level of XPG and FANCA were associated with larger tumor size (≥ pT2) at definitive surgery in TNBC.

The high expression of FANCA was related to an increase of either the Overall Survival (p = 0.0045) or the Event-Free Survival (p = 0.0141) on univariate analysis in TNBC.

Conclusions

DNA repair and cell cycle checkpoint related genes with particular regards to ERCC1/XPA in NER family, BRCA/FANC family and CHK1 may be useful as prognostic markers in TNBC and likely to be important in familial BRCA mutated cancers accordingly to their affinity. Their determination could be relevant for clinicians in selecting the proper treatment to adopt in TNBC.

Copyright information

© Ganzinelli et al; licensee BioMed Central Ltd. 2012

This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Authors and Affiliations

  • Monica Ganzinelli
    • 1
  • Enilze Ribeiro
    • 2
  • Ramona Bertoni
    • 3
    • 4
  • Letizia Bazzola
    • 4
  • Daniele Andreis
    • 4
  • Alberto Bottini
    • 4
  • Roberto Giardini
    • 3
  • Camillo Rossi
    • 5
  • Giovanna Damia
    • 1
  • Daniele Generali
    • 4
  1. 1.Istituto di Ricerche Farmacologiche Mario Negri Milan Italy, Ospedale San GerardoUniversita’ di Milano Bicocca MonzaItaly
  2. 2.Departamento de Genética, Setor de Ciencias BiologicasUniversidade Federal do ParanáCuritibaBrasil
  3. 3.U.O. di Anatomia PatologicaIstituti Ospitalieri di CremonaCremonaItaly
  4. 4.U.O. Multidisciplinare di Patologia Mammaria, Laboratorio di Oncologia Molecolare SenologicaIstituti Ospitalieri di CremonaCremonaItaly
  5. 5.Direzione SanitariaIstituti Ospitalieri di CremonaCremonaItaly

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