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.

In the last two decades, new discoveries concerning on breast cancer have contributed to important changes on its classification, from purely morphologic to molecular embased, to establish better correlation with clinicopathologic features. The classification in molecular subtypes, based on hormonal receptor and HER-2 status, have been remarkable not only for its more accurated clinical correlations, but also for its easy applicability in diagnostic routine, better replication of tumor microenvironment through the selection of paraffinized tumor amounts and cost-effectiveness of the detection method, the immunohistochemistry. Hence, this classification may predict the breast cancer prognosis and became an important target for therapy with hormonal and HER-2 antagonist drugs. Other study models, like cancer-stem cell hypothesis and immunological aspects of human cancer, have brought new emerging ideas regarding on molecular pathways and accurated prognostic preditions. Putative stem-cell markers and PD-1/PDL-1, have highlighted among several emerging molecular markers because of the bad cancer prognosis determinated by stem-cell markers expression and for emerging new drugs with selective action to PD-1/PDL-1, with promising results. The therapy of breast cancer have became diverse, target directed and personalized, in order to take in consideration the clinicopathologic cancer aspects, molecular tumor profile and clinical status of the patient.

Dedico este trabalho a minha esposa Patrícia e a meus pais, pelo amor, carinho e apoio incondicionais e por acreditarem sempre em minha capacidade e em meu trabalho e me incentivarem a persistir para vencervii viii median follow-up was 52 months, with tumor relapse in 28,6% of the cases, median relapse time of 37 months and death of 26,7% of the patients. The most frequently positive NSC markers in our study were CD24, CD44, CD133 and ESA. The other markers were positive in less than 15% of the cases. At least one NSC marker was expressed in 85% of the cases. The single most positive NSC marker was CD44, in 60,8% of the cases. In addition, two NSC profiles were defined: (1) CD24 -/ CD44+ cells and (2) CD133+ / ESA+ cells. The first NSC profile was more frequent in: (1) patients older than 40 years; (2) tumors smaller than 2,0 cm; (3) beginning tumor clinical stages (I and II); (4) and this expression increased death risk in about 4 times.The second NSC profile augmented the relapse tumor risk in about 3,75 times. All NSC markers were more frequent in high histologic grades of tumor (2 and 3). Isolated CD133 expression was more frequent in menopausal patients, while isolated CD24 expression was more frequent in tumors larger than 2,0 cm and isolated CD44 expression was more frequent in patients upper than 40 years.No significant correlation between markers was observed. Thus, immunohistochemistry is a low sensitivity method to detect NSC markers in human breast cancer, limiting the quantitative analysis of them. For this reason, there are not enough evidences to support the clinical value of NSC markers.