title: In situ identification of CD44+/CD24- cancer cells in primary human breast carcinomas.
abstract: Breast cancer cells with the CD44+/CD24- phenotype have been reported to be tumourigenic due to their enhanced capacity for cancer development and their self-renewal potential. The identification of human tumourigenic breast cancer cells in surgical samples has recently received increased attention due to the implications for prognosis and treatment, although limitations exist in the interpretation of these studies. To better identify the CD44+/CD24- cells in routine surgical specimens, 56 primary breast carcinoma cases were analysed by immunofluorescence and confocal microscopy, and the results were compared using flow cytometry analysis to correlate the amount and distribution of the CD44+/CD24- population with clinicopathological features. Using these methods, we showed that the breast carcinoma cells displayed four distinct sub-populations based on the expression pattern of CD44 and CD24. The CD44+/CD24- cells were found in 91% of breast tumours and constituted an average of 6.12% (range, 0.11%-21.23%) of the tumour. A strong correlation was found between the percentage of CD44+/CD24- cells in primary tumours and distant metastasis development (p = 0.0001); in addition, there was an inverse significant association with ER and PGR status (p = 0.002 and p = 0.001, respectively). No relationship was evident with tumour size (T) and regional lymph node (N) status, differentiation grade, proliferative index or HER2 status. In a multivariate analysis, the percentage of CD44+/CD24- cancer cells was an independent factor related to metastasis development (p = 0.004). Our results indicate that confocal analysis of fluorescence-labelled breast cancer samples obtained at surgery is a reliable method to identify the CD44+/CD24- tumourigenic cell population, allowing for the stratification of breast cancer patients into two groups with substantially different relapse rates on the basis of CD44+/CD24- cell percentage.
authors.affiliation: Department of Pathology, Campus Bio-Medico University of Rome, Rome, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Perrone
authors.forename: Laura Maria
authors.initials: LM
authors.lastname: Gaeta
authors.forename: Mariagiovanna
authors.initials: M
authors.lastname: Zagami
authors.forename: Francesca
authors.initials: F
authors.lastname: Nasorri
authors.forename: Roberto
authors.initials: R
authors.lastname: Coppola
authors.forename: Domenico
authors.initials: D
authors.lastname: Borzomati
authors.forename: Francesco
authors.initials: F
authors.lastname: Bartolozzi
authors.forename: Vittorio
authors.initials: V
authors.lastname: Altomare
authors.forename: Lucio
authors.initials: L
authors.lastname: Trodella
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Tonini
authors.forename: Daniele
authors.initials: D
authors.lastname: Santini
authors.forename: Andrea
authors.initials: A
authors.lastname: Cavani
authors.forename: Andrea Onetti
authors.initials: AO
authors.lastname: Muda
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism; D001943:Breast Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D051927:CD24 Antigen / Q000378:metabolism*; D002277:Carcinoma / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D005260:Female; D006801:Humans; D018960:Hyaluronan Receptors / Q000378:metabolism*; D016130:Immunophenotyping; D042361:Mammary Glands, Human / Q000378:metabolism; D008875:Middle Aged; D060787:Neoplasm Grading; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging
chemical_list: D014408:Biomarkers, Tumor; D051927:CD24 Antigen; D018960:Hyaluronan Receptors