uu.seUppsala University Publications
Change search
ReferencesLink to record
Permanent link

Direct link
Down-regulation of the CD3-ζ chain in sentinel node biopsies from breast cancer patients
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
Show others and affiliations
2002 (English)In: Breast Cancer Research and Treatment, ISSN 0167-6806, E-ISSN 1573-7217, Vol. 74, no 1, 33-40 p.Article in journal (Refereed) Published
Abstract [en]

Background. In several neoplastic diseases, immunosuppression has been shown to correlate with disease stage, progression, and outcome. As the prognosis for metastatic breast cancer is still pessimistic, additional strategies are being sought to improve survival. Local immunosuppression in sentinel node biopsies from 24 evaluable breast cancer patients was studied as a possible way of selecting patients for immunotherapy.

Method. Sentinel node biopsy was performed in 24 out of 25 women operated on for primary breast cancer (one was not evaluable). Specimens were snap-frozen and double-stained for the zeta-chain of the T-cell receptor. The degree of down-regulation of the zeta-chain was evaluated in three different lymph-node areas: primary follicles, secondary follicles, and paracortex.

Results. Down-regulation of varying degrees was noted in all 24 sentinel node biopsies. A high degree of down-regulation (more than 50% of T-cells not expressing zeta-chain) was seen in the primary follicles in six patients (25%), in the secondary follicles in 13 patients (72%), and in the paracortex in 19 patients (79%).

Conclusion. Local down-regulation of an immune function parameter was seen in sentinel node biopsies from breast cancer patients. In addition to possible prognostic implications, the sentinel node might be an appropriate location for detecting early-stage immunological down-regulation, which might open a possibility of selecting patients who could benefit from immunotherapy.

Place, publisher, year, edition, pages
2002. Vol. 74, no 1, 33-40 p.
Keyword [en]
breast cancer, CD3, down-regulation, immunology, sentinel node, T-cell receptor, zeta-chain
National Category
Medical and Health Sciences
URN: urn:nbn:se:uu:diva-95902DOI: 10.1023/A:1016009913699ISI: 000176413600005OAI: oai:DiVA.org:uu-95902DiVA: diva2:170277
Available from: 2007-05-11 Created: 2007-05-11 Last updated: 2012-08-22Bibliographically approved
In thesis
1. Sentinel Node Biopsy in Breast Cancer: Clinical and Immunological Aspects
Open this publication in new window or tab >>Sentinel Node Biopsy in Breast Cancer: Clinical and Immunological Aspects
2007 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

The most important prognostic factor in breast cancer is the axillary lymph node status. The sentinel node biopsy (SNB) is reported to stage the axilla with an accuracy > 95 % in early breast cancer. Tumour-related perturbation of T-cell function has been observed in patients with malignancies, including breast cancer. The down-regulation of the important T-cell activation molecules CD3-ζ and CD28 may cause T-cell dysfunction, anergy, tolerance and deletion.

The expression of CD3-ζ and CD28 was evaluated in 25 sentinel node biopsies. The most pronounced down-regulation was seen in the paracortical area, where the best agreement between both parameters was observed. CD28 expression was significantly more suppressed in CD4+ than in CD8+ T-cells.

From the Swedish sentinel node database, 109 patients with breast cancer > 3 cm planned for both SNB and a subsequent axillary dissection were identified. The false negative rate (FNR) was 12.5%. Thirteen cases of tumour multifocality were detected on postoperative pathology. The FNR in this subgroup was higher (30.8%) than in patients with unifocal disease (7.8%; P = 0.012).

From the Swedish SNB multicentre cohort trial, 2246 sentinel node-negative patients who had not undergone further axillary surgery were selected for analysis. After a median follow-up time of 37 months (range 0-75), 13 isolated axillary recurrences (13/2246; 0.6%) were found. In another 14 cases, local or distant failure preceded or coincided with axillary relapse (27/2246; 1.2%).

In conclusion, the immunological analysis of the sentinel node might provide valuable prognostic information and aid selection of patients for immunotherapy. SNB is encouraged in breast cancer larger than 3 cm, if no multifocal growth pattern is present. The axillary recurrence rate after a negative SNB in Sweden is in accordance with international figures. However, a longer follow-up is mandatory before the true failure rate of the SNB can be determined.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2007. 55 p.
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 259
Surgery, breast cancer, tumour immunology, sentinel node biopsy, CD3-zeta, CD28, Kirurgi
urn:nbn:se:uu:diva-7890 (URN)978-91-554-6897-2 (ISBN)
Public defence
2007-06-01, Aulan, Ingång 21, Centrallasarettet, 72189 Västerås, 13:15
Available from: 2007-05-11 Created: 2007-05-11Bibliographically approved

Open Access in DiVA

No full text

Other links

Publisher's full text

Search in DiVA

By author/editor
Bergkvist, Leif
By organisation
Centre for Clinical Research, County of Västmanland
In the same journal
Breast Cancer Research and Treatment
Medical and Health Sciences

Search outside of DiVA

GoogleGoogle Scholar
The number of downloads is the sum of all downloads of full texts. It may include eg previous versions that are now no longer available

Altmetric score

Total: 247 hits
ReferencesLink to record
Permanent link

Direct link