Journal of Cancer Research and Clinical Oncology

, Volume 135, Issue 9, pp 1185–1195

Diagnostic accuracy of small breast epithelial mucin mRNA as a marker for bone marrow micrometastasis in breast cancer: a pilot study

  • Manuel Valladares-Ayerbes
  • Pilar Iglesias-Díaz
  • Silvia Díaz-Prado
  • Daniel Ayude
  • Vanessa Medina
  • Mar Haz
  • Margarita Reboredo
  • Silvia Antolín
  • Lourdes Calvo
  • Luis M. Antón-Aparicio
Original Paper

Abstract

Background

Detection of isolated tumour cells (ITC) in the blood or minimal deposits in distant organs such as bone marrow (BM) could be important to identify breast cancer patients at high risk of relapse or disease progression. PCR amplification of tissue or tumour selective mRNA is the most powerful analytical tool for detection of this micrometastasis. We have evaluated for the first time, the diagnostic accuracy of small breast epithelial mucin (SBEM) as a potential marker for BM micrometastasis in breast cancer.

Methods

A nested RT-PCR assay for detection of SBEM mRNA was compared with immunocytochemistry (ICC) with anticytokeratin AE1/AE3 antibody in paired samples obtained from the BM of breast cancer patients. Associations of SBEM mRNA detection in BM and clinical and pathological parameters were evaluated. SBEM mRNA status and time to breast cancer progression were analysed using Kaplan–Meyer curves.

Results

Fifty stages I–IV breast cancer female patients were prospectively included in our study. SBEM specific transcript was found in BM in 26% of the patients. Detection rate was similar to the percentage of patients with ITCs detected using ICC (24%). SBEM mRNA in BM aspirates were significantly associated with presence of clinically active disease, including locally advanced and metastatic patients (47%, P = 0.021) and tumours with positive hormonal receptors (36.7%, P = 0.035). In addition association with Her2/neu over-expression (44.4%, P = 0.051) and low proliferating tumours (36%, P = 0.067) were close to significant levels. When we analysed time to breast cancer progression adjusting for grade or hormone receptor status, presence of SBEM mRNA in BM defines distinct prognostic groups.

Conclusions

SBEM might represent a suitable marker for molecular detection of ITCs in BM in breast cancer patients. Analysis of prognostic value for SBEM mRNA-based assay should take into account the heterogeneity and different molecular subtypes of breast cancer.

Keywords

Isolated tumour cells Small breast epithelial mucin Breast tumour cells Minimal disease RNA-based methods 

Abbreviations

ITC

Isolated tumour cells

ICC

Immunocytochemistry

CK

Cytokeratin

RT-PCR

Reverse-transcriptase polymerase-chain reaction

SBEM

Small breast epithelial mucin

BM

Bone marrow

TTP

Time to breast cancer progression

HR

Hormonal receptors

Copyright information

© Springer-Verlag 2009

Authors and Affiliations

  • Manuel Valladares-Ayerbes
    • 1
    • 2
  • Pilar Iglesias-Díaz
    • 3
  • Silvia Díaz-Prado
    • 2
    • 4
  • Daniel Ayude
    • 2
    • 5
  • Vanessa Medina
    • 2
  • Mar Haz
    • 2
  • Margarita Reboredo
    • 1
  • Silvia Antolín
    • 1
  • Lourdes Calvo
    • 1
  • Luis M. Antón-Aparicio
    • 1
    • 4
  1. 1.Medical Oncology DepartmentLa Coruña University HospitalLa CoruñaSpain
  2. 2.Oncology Research ProgramBiomedical Research Institute (INIBIC)La CoruñaSpain
  3. 3.Pathology DepartmentLa Coruña University HospitalLa CoruñaSpain
  4. 4.Medicine DepartmentLa Coruña UniversityLa CoruñaSpain
  5. 5.PontevedraSpain

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