Detection of Putative Stem-cell Markers in Invasive Ductal Carcinoma of the Breast by Immunohistochemistry: Does It Improve Prognostic/Predictive Assessments?

Abstract

Introduction:Experimental evidences from the last 2 decades supports the existence of a special type of neoplastic cell with stem-like features [cancer stem cell (CSC)] and their role in the pathophysiology and therapeutic resistance of breast cancer. However, their clinical value in human breast cancer has not been fully determined.Materials and Methods:An immunohistochemistry panel of 10 putative CSC markers (CD34, C-KIT, CD10, SOX-2, OCT 3/4, p63, CD24, CD44, CD133, and ESA/EPCAM) was applied to 74 cases of breast cancer, followed in a Regional Cancer Center of Minas Gerais State, Brazil, from 2004 to 2006. Possible associations between CSC markers and classic variables of clinicopathologic relevance were investigated.Results:The most frequently positive CSC markers were CD44, CD24, CD133, and ESA (the others were present in <15% of the cases). Two CSC profiles were defined: CD24−/CD44+ (CSC-1) and CD133+/ESA+ (CSC-2). CSC-1 was significantly associated to patients older than 40 years, tumors of <2.0 cm in diameter, early clinical stages (P<0.05), and increased death risk of 4 times (P=0.03; 95% confidence interval, 1.09-14.41). CSC-2 was related to increased relapse risk of 3.75 times (P=0.04; 95% confidence interval, 1.02-13.69).Conclusion:The detection of the most frequently positive CSC markers by immunohistochemistry is of clinicopathologic and prognostic relevance.

CD133 in Breast Cancer Cells: More than a Stem Cell Marker

“…In fact, the number of CD133 + cells ranged between 1 and 10% in claudin-low cells, reached 80% in basal-like cell lines, and were between 1 and 2% in both luminal and HER2 + cells, questioning the equivalence between CD133 levels and stem-like properties in breast tumor cells [18]. For this reason, although also recently it was used as the sole marker of CSCs [19], CD133 belongs to a well-known panel of molecules that, when properly combined, can actually identify cells with a stem-like phenotype in breast cancer cell lines and primary tumors with different phenotypes [13, 20].…”

CD34 cells in somatic, regenerative and cancer stem cells: Developmental biology, cell therapy, and omics big data perspective

“…The roles of CD34 have also been implicated in many cellular processes including cell adhesion and signal transduction mechanisms . Interestingly, expression of CD34 has also been reported on cancer stem cells (CSCs) . In future, it will be interesting to investigate the role(s) of CD34 in various types of CSCs.…”

Advances in Molecular and Immunohistochemical Detection of Prognostic and Therapeutic Markers in Breast Cancer

“…It has been hypothesized that cancer stem-cell might be one of the causes of the high variability of biological and prognostic spectrum of breast cancer. Cancer-stem cells might play an important role on therapeutic resistance and progression of disease, affecting the overall and free of disease survival [31,32].…”

“…Tumoral cells in active proliferation phase are more hitten, increasing the proportion of indolent cells with stem-like features in cancer cell population. Through the capacity of multilineage differentiation, cancer stem cells might generate new daughter cells with more aggressiveness and chemoresistance [32,34].…”

“…In this way, these cells are better identified through "in vitro" methods, like cellular cultures. However, the mainly disadvantage of this technique is the fact of stem cells behave in a different fashion in artificial environment, since the cell phenotype expression depends on their interactions [32,35].…”