Immunohistochemical analysis of cancer stem cell markers in invasive breast carcinoma and associated ductal carcinoma in situ: relationships with markers of tumor hypoxia and microvascularity

• Published in: Human pathology 2013-03, Vol.44 (3), p.402-411
• Main Authors: Currie, Margaret J., PhD, Beardsley, Brooke E., MBChB, Harris, Gavin C., FRCPath, Gunningham, Sarah P., PhD, Dachs, Gabi U., PhD, Dijkstra, Birgit, FRACS, Morrin, Helen R., BSc, Wells, J. Elisabeth, PhD, Robinson, Bridget A., MD
• Format: Article
• Language: English
• Subjects: AC133 Antigen; ALDH1; Angiogenesis; Antigens, CD - metabolism; Banks; Biomarkers, Tumor - metabolism; Breast cancer; Breast Neoplasms - blood supply; Breast Neoplasms - metabolism; Breast Neoplasms - pathology; Cancer therapies; Carcinoma, Ductal, Breast - blood supply; Carcinoma, Ductal, Breast - metabolism; Carcinoma, Ductal, Breast - pathology; Carcinoma, Intraductal, Noninfiltrating - blood supply; Carcinoma, Intraductal, Noninfiltrating - metabolism; Carcinoma, Intraductal, Noninfiltrating - pathology; CD133; CD24 Antigen - metabolism; CD44+/CD24−/low; Chemotherapy; Cloning; Cohort Studies; Female; Gene expression; Genotype & phenotype; Glycoproteins - metabolism; Humans; Hyaluronan Receptors - metabolism; Hypoxia; Immunohistochemistry; Isoenzymes - metabolism; Microvessels; Middle Aged; Neoplastic Stem Cells - metabolism; Neoplastic Stem Cells - pathology; Pathology; Patients; Peptides - metabolism; Retinal Dehydrogenase - metabolism; Retrospective Studies; Stem cells; Tumors; Womens health
• ISSN: 0046-8177; 1532-8392
• DOI: 10.1016/j.humpath.2012.06.004

Summary We performed immunohistochemical analysis of 3 cancer stem cell–related markers (CD44+ /CD24−/low , aldehyde dehydrogenase [ALDH]-1, CD133) in 94 invasive ductal carcinomas and assessed relationships with markers of hypoxia (carbonic anhydrase IX [CAIX]), tumor microvessel density (CD31), and clinicopathologic variables. Overall, 10% of tumors were CD44+ /CD24−/low , 13% were ALDH-1+ , 25% were CD133+ , 35% were immunonegative, and 1 tumor was immunopositive for all 3 markers. Associated ductal carcinoma in situ (DCIS) was present in 48% of tumors. Marker immunopositivity was detected in DCIS in 13% (CD44+ /CD24−/low ), 7% (ALDH-1+ ), and 32% (CD133+ ) of these tumors and was more likely present in DCIS when also detected in the invasive compartment ( P = .03, P = .001, and P = .009, respectively). CD44+ /CD24−/low cells were more common in progesterone receptor–negative tumors ( P < .01), and ALDH-1+ cells were more common in estrogen receptor–negative tumors ( P < .01). CD133+ cells were more common in patients younger than 50 years ( P < .05) and in high grade ( P < .01), localized ( P < .05), and estrogen receptor–negative ( P < .001), progesterone receptor–negative ( P = .02), and triple-negative breast cancers ( P < .001). CD44+ /CD24−/low ( P = .06) and CD133+ ( P = .02) tumor cells were more common in CAIX+ versus CAIX− tumors, whereas ALDH-1+ tumors had a higher mean microvessel density than did ALDH-1− tumors ( P = .002). No significant relationships were observed between the markers studied and survival for 5 years. Our study demonstrated the presence of cancer stem cell marker–positive tumor cells in DCIS as well as invasive breast cancer and showed that CD44+ /CD24−/low and CD133+ cells were more frequently observed in hypoxic regions of tumor, whereas ALDH-1+ cells more commonly colocalized to tumors with high microvessel density.