Ines V Gruber1, Andreas D Hartkopf2, Markus Hahn2, Florin-Andrei Taran2, Annette Staebler3, Diethelm Wallwiener2, Sara Y Brucker2, Julia Hanke4, Tanja Fehm5. 1. Department of Obstetrics and Gynecology, University of Tuebingen, Tuebingen, Germany ines.gruber@med.uni-tuebingen.de. 2. Department of Obstetrics and Gynecology, University of Tuebingen, Tuebingen, Germany. 3. Department of Pathology, University of Tuebingen, Tuebingen, Germany. 4. HELIOS Clinic Berlin-Buch, Department of Gynecology and Obstetrics, Berlin, Germany. 5. Department of Obstetrics and Gynecology, University of Duesseldorf, Duesseldorf, Germany.
Abstract
BACKGROUND/AIM: By definition, tumor cells do not pass the epithelial basement membrane in pre-invasive lesions. However, recently, it was shown that hematogenous tumor cell dissemination already takes place in patients with ductal carcinoma in situ (DCIS), giving disseminated tumor cells (DTCs) in the bone marrow the opportunity to interact with the peripheral immune system. We, therefore, investigated the relationship between DTCs and the peripheral innate and adaptive immune system of DCIS patients, as immunosurveillance might also be impaired in pre-invasive lesions. MATERIALS AND METHODS: We analyzed the peripheral immune status of 115 DCIS patients by flow cytometry. Results were correlated with presence of DTCs, that were detected in the bone marrow by immunocytochemistry (pan-cytokeratin antibody A45-B/B3) using the automated cellular imaging system (ACIS) according to the international society of hematotherapy and graft engineering (ISHAGE) evaluation criteria. Apoptotic DTCs were characterized by positive M30 staining and cytomorphological criteria. RESULTS: In contrast to breast cancer, we found no significant correlation between appearance of DTCs and quantitative distribution of T-cell sub-populations, B and NK-cells neither in the bone marrow nor in the peripheral blood. Moreover, DTCs did not affect the expression of important immunomodulatory antigens for functional integrity of specific immune response such as, TCR-ζ, CD28 or CD95. Interestingly, 39% of DTCs were positive for M30 expression and showed cytomorphological signs of apoptosis. CONCLUSION: In contrast to breast cancer, DTCs of DCIS seem to be less immunogenic, which might result in a diverging way to evade immunosurveillance. Copyright
BACKGROUND/AIM: By definition, tumor cells do not pass the epithelial basement membrane in pre-invasive lesions. However, recently, it was shown that hematogenous tumor cell dissemination already takes place in patients with ductal carcinoma in situ (DCIS), giving disseminated tumor cells (DTCs) in the bone marrow the opportunity to interact with the peripheral immune system. We, therefore, investigated the relationship between DTCs and the peripheral innate and adaptive immune system of DCIS patients, as immunosurveillance might also be impaired in pre-invasive lesions. MATERIALS AND METHODS: We analyzed the peripheral immune status of 115 DCIS patients by flow cytometry. Results were correlated with presence of DTCs, that were detected in the bone marrow by immunocytochemistry (pan-cytokeratin antibody A45-B/B3) using the automated cellular imaging system (ACIS) according to the international society of hematotherapy and graft engineering (ISHAGE) evaluation criteria. Apoptotic DTCs were characterized by positive M30 staining and cytomorphological criteria. RESULTS: In contrast to breast cancer, we found no significant correlation between appearance of DTCs and quantitative distribution of T-cell sub-populations, B and NK-cells neither in the bone marrow nor in the peripheral blood. Moreover, DTCs did not affect the expression of important immunomodulatory antigens for functional integrity of specific immune response such as, TCR-ζ, CD28 or CD95. Interestingly, 39% of DTCs were positive for M30 expression and showed cytomorphological signs of apoptosis. CONCLUSION: In contrast to breast cancer, DTCs of DCIS seem to be less immunogenic, which might result in a diverging way to evade immunosurveillance. Copyright