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Hematogenous and lymphatic tumor cell dissemination may be detected in patients diagnosed with ductal carcinoma in situ of the breast

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Abstract

Tumor cell dissemination in bone marrow (BM) and lymph nodes is considered an important step in systemic disease progression and is associated with poor prognosis. Only invasive cancers are assumed to shed isolated tumor cells (ITC) into the bloodstream and infiltrate lymph nodes. However, latest studies indicate that tumor cell dissemination may occur before stroma invasion, i.e., in ductal carcinoma in situ (DCIS). Therefore, the purpose of this study was to examine the incidence of ITC in bone marrow and sentinel lymph nodes (SN) in patients diagnosed with DCIS and its correlation with clinicopathological factors. 266 patients who were treated at the Department of Gynecology and Obstetrics (University Hospital Tuebingen, Germany) between 2003 and 2009 with DCIS were included into this study. BM aspirates were analyzed by immunocytochemistry (pancytokeratin antibody A45-B/B3) using ACIS system (Chromavision) according to the ISHAGE evaluation criteria. SN were analyzed in 221 of these patients by extensive step sectioning and hematoxylin–eosin staining. In 34 of 266 patients (13%), ITC in BM could be detected. There was no correlation found between tumor size, grading, histology, or Van Nuys Prognostic Index and tumor cell dissemination. In two cases, metastatic spread into lymph nodes was observed (pN1mi), whereas in one case, ITC in lymph nodes were detected; however, additional sectioning and immunohistochemical staining of the primary lesion in the cases with positive SN did not reveal invasive cancer. Interestingly, all the three patients were BM negative. Tumor cell dissemination may be detected in patients diagnosed with DCIS. Either these cells have started already to disseminate from preinvasive mammary lesions or from occult invasive tumors or represent the earliest step of microinvasion in a preinvasive lesion. The clinical relevance of these cells has to be further evaluated.

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Abbreviations

BM:

Bone marrow

CK:

Cytokeratin

DIN:

Ductal intraepithelial neoplasia

DCIS:

Ductal carcinoma in situ

DTC:

Disseminated tumor cell(s)

HE:

Hematoxylin-eosin

ITC:

Isolated tumor cell

n.s.:

Not significant

SN:

Sentinel node

SLNB:

Sentinel lymph node biopsy

VNPI:

Van Nuys Prognostic Index

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Acknowledgments

The authors thank Professor Ludwig Spätling (Department of Gynecology and Obstetrics, Klinikum Fulda) and Dr. Mustafa Aydogdu (Department of Gynecology and Obstetrics, Klinikum Bremen-Mitte) for their respective supports.

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Authors and Affiliations

  1. Department of Obstetrics and Gynecology, University of Tuebingen, Calwerstrasse 7, 72076, Tuebingen, Germany

    Malgorzata Banys, Ines Gruber, Natalia Krawczyk, Sven Becker, Diethelm Wallwiener, Jolanta Jakubowska, Jürgen Hoffmann, Ralf Rothmund & Tanja Fehm

  2. Department of Pathology, University of Tuebingen, Calwerstrasse 7, 72076, Tuebingen, Germany

    Ralph Kurth & Annette Staebler

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  1. Malgorzata Banys
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  2. Ines Gruber
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  3. Natalia Krawczyk
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  11. Tanja Fehm
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Correspondence to Tanja Fehm.

Additional information

Malgorzata Banys and Ines Gruber contributed equally to this work.

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Banys, M., Gruber, I., Krawczyk, N. et al. Hematogenous and lymphatic tumor cell dissemination may be detected in patients diagnosed with ductal carcinoma in situ of the breast. Breast Cancer Res Treat 131, 801–808 (2012). https://doi.org/10.1007/s10549-011-1478-2

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  • DOI: https://doi.org/10.1007/s10549-011-1478-2

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