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

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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.

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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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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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Authors and Affiliations

  1. First Department of Obstetrics & Gynecology, Ludwig Maximilians University of Munich, Maistrasse 11, D-80337, Munich, Germany

    Christian Schindlbeck, Udo Jeschke, Sandra Schulze, Wolfgang Janni, Brigitte Rack, Harald Sommer & Klaus Friese

  2. Max Delbrück Center for Molecular Medicine, R.-Rössle-Street 10, D-13125, Berlin-Buch, Germany

    Uwe Karsten

  3. Burnham Institute for Medical Research, 10901 N. Torrey Pines Road, La Jolla, CA, 92037-1062, USA

    Stan Krajewski

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  1. Christian Schindlbeck
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Correspondence to Christian Schindlbeck.

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Schindlbeck, C., Jeschke, U., Schulze, S. et al. Prognostic impact of Thomsen–Friedenreich tumor antigen and disseminated tumor cells in the bone marrow of breast cancer patients. Breast Cancer Res Treat 101, 17–25 (2007). https://doi.org/10.1007/s10549-006-9271-3

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  • DOI: https://doi.org/10.1007/s10549-006-9271-3

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