Сd44+/Cd24− Markers of Cancer Stem Cells in Patients With Breast Cancer of Different Molecular Subtypes

Abstract

Aim: To determine frequency of tumors with immunohistochemical markers of cancer stem cells (CSC) CD44+/CD24− in patients with breast cancer (BC) of different molecular subtype and to evaluate their prognostic value. Object: Surgical material of 132 patients with BC stage I–II, age from 23 to 75 years, mean age — 50.2 ± 3.1 years was studied. Methods: Clinical, immunohistochemical (expression CD44+/CD24−), morphological, statistical. Results: BC is characterized by heterogeneity of molecular subtypes and expression of markers (CD44+/CD24−). Immunohistochemical study of expression of CSC markers in surgical material has detected their expression in 34 (25.4%) patients with BC of different molecular subtypes. The highest frequency of cells with expression of CSC marker was observed in patients with basal molecular subtype (44.8% patients). Most of BC patients with phenotype CD44+/CD24 had stage I of tumor process (34.3%). Statistical processing of data has showen that Yule colligation coefficient equaled 0.28 (р > 0.05) that argues poor correlation between stage of tumor process and number of tumors with positive expression of CSC markers. Statistical processing of data has showen high correlation between presence of cells with expression of CSC markers and metastases of BC in regional lymph nodes (Yule colligation coefficient equals 0.943; р < 0.5). Difference in overall survival of patients with BC of basal molecular subtype depending on expression of CSC CD44+/CD24− markers was detected. Survival of patients with basal BC was reliably higher at lack in tumors of cells with CSC markers CD44+/CD24− and, correspondingly, lower at presence of such cells (р < 0.05). In patients with BC of luminal (A and B), HER-2-positive subtypes, significant change in survival of patients depending on expression of CSC markers was not determined (р > 0.05). Conclusion: Significance of tumor cells with markers CD44+/CD24− within the limits of molecular subtype of BC may be additional criterion for advanced biological characteristic of BC, and in patients with BC of basal molecular subtype — for predictive evaluation of individual potential of tumor to aggressive clinical course.

Enrichment of CD44 in basal-type breast cancer correlates with EMT, cancer stem cell gene profile, and prognosis

“…This agrees with a previous study showing that patients with CSC markers CD44(+)/CD24(−) had a lower survival rate, while patients without this subpopulation had a higher survival rate in basal-like breast cancer. 89 Some studies showed that CD44 expression was positively correlated with the metastasis of breast carcinoma, 75 but others reported opposite results. 90 Martin and Jiang found that CD44 was markedly reduced in patients with ductal breast cancer with metastasis.…”

<p>Targeting stem cells in the realm of drug-resistant breast cancer</p>

“…Different subtypes of BC constitute different proportion of BCSCs contributing to different disease outcome. Among the BC subtypes, the highest amount of CSCs was observed in patients with TNBC (basal) subtype and has been correlated with its aggressiveness 64…”

A correlation study of the expression of HA-CD44st and HER-2 in breast cancer

“…The interaction between HA and CD44 also contributes to the resistance of HER-positive breast cancer cells to trastuzumab 20 and is associated with poor prognosis in breast cancer patients. 30 – 33 Recent studies reported that the binding of HA to CD44 can modulate the activity of EGFR family members. 14 The serum CD44 concentration was a significant predictor of overall survival for patients with HER-2-positive breast cancer, which suggested that CD44 should be investigated further for its potential as a prognostic biomarker.…”