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Hyaluronan synthases (HAS1–3) in stromal and malignant cells correlate with breast cancer grade and predict patient survival
- Source :
- Breast Cancer Research and Treatment. 143:277-286
- Publication Year :
- 2013
- Publisher :
- Springer Science and Business Media LLC, 2013.
-
Abstract
- Accumulation of hyaluronan (HA) in pericellular stroma and carcinoma cells is predictive of unfavorable patient prognosis in many epithelial cancers. However, it is not known whether the HA originates from carcinoma or stromal cells, or whether increased expression of hyaluronan synthase proteins (HAS1-3) contributes to HA accumulation. In this study, localization and expression of HAS1-3 were evaluated immunohistochemically in 278 cases of human breast cancer, and correlated with prognostic factors and patient outcome. Both carcinoma cells and stromal cells were HAS-positive. In carcinoma cells, HAS1 and HA stainings correlated with each other, and HAS1 associated with estrogen receptor negativity, HER2 positivity, high relapse rate, and short overall survival. In stromal cells, the staining levels of all HAS isoforms correlated with the stromal HA staining, stromal cell CD44, high relapse rate, and short overall survival of the patients. In addition, expression levels of stromal HAS1 and HAS2 were related to obesity, large tumor size, lymph node positivity, and estrogen receptor negativity. Thus, stromal HAS1 and HAS3 were independent prognostic factors in the multivariate analysis. The data suggest that increased levels of HAS enzymes contribute to the accumulation of HA in breast cancer, and that HA is synthesized in carcinoma cells and stromal cells. The study also indicates that HAS enzyme levels are related to tumor aggressiveness and poor patient outcome representing potential targets for therapy.
- Subjects :
- Adult
Cancer Research
Pathology
medicine.medical_specialty
Stromal cell
Survival
Receptor, ErbB-2
Estrogen receptor
Breast Neoplasms
Antibodies, Monoclonal, Humanized
Breast cancer
Carcinoma
Humans
Medicine
Obesity
RNA, Messenger
Glucuronosyltransferase
Hyaluronic Acid
Lymph node
Aged
Aged, 80 and over
biology
business.industry
CD44
Cancer
Middle Aged
Trastuzumab
medicine.disease
Survival Analysis
Hyaluronan synthase
Hyaluronan Receptors
medicine.anatomical_structure
Oncology
biology.protein
Female
Neoplasm Grading
Neoplasm Recurrence, Local
Stromal Cells
business
Hyaluronan Synthases
Subjects
Details
- ISSN :
- 15737217 and 01676806
- Volume :
- 143
- Database :
- OpenAIRE
- Journal :
- Breast Cancer Research and Treatment
- Accession number :
- edsair.doi.dedup.....aded06f49f03f03ea4dcea24d6376cd8