Hematopoietic progenitor cells (HPCs) in node-negative invasive breast carcinomas: Immunohistochemical analysis and clinico-pathological correlations

Using immunohistochemistry, we investigated 603 negative lymph nodes from 51 patients affected by invasive breast cancer (BC) to recognize bone marrow-derived hematopoietic progenitor cells (HPCs). HPC aggregates, revealed by CD34, CD133, VEGFR1, and CD117 antisera, were determined by an intensity-distribution score (ID). Cases with an ID-score >3 at least for one marker were considered to strongly express HPCs. Twenty-five of 51 (49%) high expressor patients were identified by CD34 antiserum, while 24/51 (47.1%), 17/51 (33.3%), and 15/51 (29.4%) were identified by CD117, CD133, and VEGFR1, respectively. No significant relationships were found between HPCs status and histotype, tumor grade, stage, and hormone receptors, as determined at the moment of the first diagnosis. A significant correlation was recorded for Ki-67 values, as well as for death from invasive BC. No statistical significance was achieved regarding HER2 status, although a tendency toward a statistically significant P value was obtained. A significant relationship (P < 0.001) was found between high expressors of HPC and progression of disease, documented by the development of distant metastases. An equivalent P value was ascertained for osseous localizations, with a lesser value in other metastatic sites. Regarding the appearance of distant metastases, the greatest efficiency value was obtained by CD133 (85.7%). Overall survival (OS) and distant metastases-free survival (DMFS) revealed a high statistical significance for HPC expression, Ki-67 values, and HER2 status. By multivariate analysis, HPC expression and Ki-67 values emerged as the higher independent prognostic variables in the analysis of DMFS and OS, respectively.