Glycodelin expression associates with differential tumour phenotype and outcome in sporadic and familial non-BRCA1/2 breast cancer patients
| Autor: | Päivi Heikkilä, Riitta Koistinen, Heli Nevanlinna, Tuomas Heikkinen, Hannu Koistinen, Laura Hautala, Kristiina Aittomäki, Dario Greco, Carl Blomqvist |
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| Rok vydání: | 2010 |
| Předmět: |
Adult
Cancer Research Breast Neoplasms Pregnancy Proteins Biology Disease-Free Survival Metastasis Young Adult Cyclin D1 Breast cancer medicine Humans skin and connective tissue diseases Genetic Association Studies Aged Glycoproteins Proportional Hazards Models Aged 80 and over BRCA2 Protein Tissue microarray Glycodelin BRCA1 Protein Gene Expression Profiling Cancer Middle Aged medicine.disease Phenotype Oncology Tissue Array Analysis Multivariate Analysis Mutation PAEP Cancer research Female Breast disease |
| Zdroj: | Breast Cancer Research and Treatment. 128:85-95 |
| ISSN: | 1573-7217 0167-6806 |
| DOI: | 10.1007/s10549-010-1065-y |
| Popis: | Glycodelin (encoded by PAEP gene) is a secreted lipocalin protein mainly expressed in reproductive tissues, but also in several tumour types. In the breast, glycodelin is expressed both in normal epithelial and cancerous tissue. To investigate the association of glycodelin with clinicopathological features of breast cancer and outcome of patients we evaluated the protein expression of glycodelin in a large series of breast tumours. Immunohistochemical analysis of tissue microarrays was used to study glycodelin expression on 399 sporadic and 436 familial non-BRCA1/2 tumours with strong family history. Gene expression analysis was used to define genes co-expressed with PAEP in sporadic and familial non-BRCA1/2 breast tumours. In the sporadic series, the glycodelin expression associated with low proliferation rate (P < 0.001), with a tendency towards well-differentiated tumours (grades 1 and 2, P = 0.012) and high cyclin D1 (P = 0.034) expression. However, in familial non-BRCA1/2 cases with strong family history glycodelin expression associated with a less favourable phenotype, i.e. positive lymph node status (P = 0.003) and HER2-positive tumours (P = 0.009). Moreover, the patients with glycodelin-positive tumours had an increased risk for distant metastases (P = 0.001) and in multivariate analysis glycodelin expression was an independent predictor of metastasis (hazard ratio (HR) = 2.22, 95% confidence interval (95% CI) = 1.22–4.03, P = 0.009) in familial non-BRCA1/2 breast cancer. Gene expression analysis further revealed different gene expression profiles correlating with the PAEP expression in the sporadic and familial non-BRCA1/2 breast cancers. Our findings suggest differential progression pathways in the sporadic and familial non-BRCA1/2 breast tumours expressing glycodelin. |
| Databáze: | OpenAIRE |
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