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Breast Cancer Research and Treatment

, Volume 101, Issue 1, pp 17–25 | Cite as

Prognostic impact of Thomsen–Friedenreich tumor antigen and disseminated tumor cells in the bone marrow of breast cancer patients

  • Christian Schindlbeck
  • Udo Jeschke
  • Sandra Schulze
  • Uwe Karsten
  • Wolfgang Janni
  • Brigitte Rack
  • Stan Krajewski
  • Harald Sommer
  • Klaus Friese
PRECLINICAL STUDY

Abstract

Purpose

The Thomsen–Friedenreich antigen (TF, CD176) is a specific oncofetal carbohydrate epitope (Galβ1-3GalNAcα-O-Ser/Thr) expressed on the surface of various carcinomas. It mediates endothelium adhesion and formation of metastases. As it also causes immune response, its prognostic impact is indeterminate. The presence of disseminated tumor cells in the bone marrow of breast cancer patients (DTC-BM) indicates worse prognosis. We examined the expression of TF in primary breast cancer tissue of 265 patients with known BM status at the time of first diagnosis.

Methods

BM aspiration, cytospin preparation and immunocytochemical staining with the anti-Cytokeratin antibody A45 B/B3 was done following a standardised protocol. TF expression was examined immunohistochemically on Tissue Micro Arrays (TMA) with the anti-TF antibody A78-G/A7. Evaluation was done using the immunoreactive score (IRS).

Results

Median IRS for TF expression was 2 (0–12). 68 of 265 patients (25.7%) showed DTC-BM with a median of 2/2 × 106 cells (1–1500). There was no correlation between TF expression and DTC-BM. After a median follow up of 60.1 months (7–119), the detection of DTC-BM showed prognostic significance for overall survival (OS, p = 0.034), whereas TF positivity (IRS > 2) indicated prolonged disease-free (p = 0.01), distant disease-free (p = 0.005), and overall survival (p = 0.005).

Discussion

Patients with TF-positive tumors had a significantly better prognosis. Dissemination routes, TF-mediated metastasis formation, and the immunogeneity of TF might determine the prognostic impact of TF expression in different tumor entities. Further characterisation of primary tumors and DTC-BM could help to improve the biological understanding of metastases and develop targeted therapies.

Keywords

Breast cancer Disseminated tumor cells Bone marrow Minimal residual disease  Thomsen–Friedenreich-antigen Prognosis  Metastasis Immune response Therapy 

Abbreviations

ABC

avidin-biotin-complex

APAAP

alkaline phosphatase anti-alkaline phosphatase

BM

bone marrow

CK

cytokeratin

DAB

3,3 diaminobenzidin

DDFS

distant disease free survival

DFS

disease free survival

DTC

disseminated tumor cells

EPCAM

epithelial platelet cell adhesion molecule

ER

estrogen receptor

FISH

fluorescence in situ hybridisation

HA

hemangiosis

HER2

human epithelial growth factor receptor 2

H&E

hematoxylin eosin

ICC

immunocytochemistry

IHC

immunohistochemistry

IRS

immuno-reactive score

LA

lymphangiosis

LN

lymph node

OS

overall survival

PBS

phosphate buffered saline

Pts

patients

TF

Thomsen–Friedenreich antigen

TMA

tissue micro array

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Notes

Acknowledgements

We thank Mrs. S. Schulze for excellent technical assistance. We are grateful to Mrs. X. Huang for skilful TMAs preparation and Mr. S. Banares for manuscript editing.

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Copyright information

© Springer Science+Business Media B.V. 2006

Authors and Affiliations

  • Christian Schindlbeck
    • 1
  • Udo Jeschke
    • 1
  • Sandra Schulze
    • 1
  • Uwe Karsten
    • 2
  • Wolfgang Janni
    • 1
  • Brigitte Rack
    • 1
  • Stan Krajewski
    • 3
  • Harald Sommer
    • 1
  • Klaus Friese
    • 1
  1. 1.First Department of Obstetrics & GynecologyLudwig Maximilians University of MunichMunichGermany
  2. 2.Max Delbrück Center for Molecular MedicineBerlin-BuchGermany
  3. 3.Burnham Institute for Medical ResearchLa JollaUSA

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