Three ABC transporters (MDR1, MRP1, BCRP), belonging to the family of multidrug resistance (MDR) proteins, play a crucial role in the protection mechanisms during embryogenesis and mediate drug resistance in cancer cells. The distribution of these transporters in the series of human embryonal/fetal intestine, liver and kidneys of various stages of intrauterine development (IUD) by indirect two-step immunohistochemical method was investigated. The organ- and age-specific expression patterns of these transporters were depicted and compared with the expression in adult organs. The evaluation of intestine and liver samples demonstrate differences in expression pattern of ABC transporters during IUD. On the contrary, in kidneys the age-specific localization was not observed. However, the increasing positivity from the kidney surface towards deeper, more differentiated parts was found. Hopefully, our study may contribute to elucidation of the role of multidrug resistance (MDR) pathways during IUD in man.
- MeSH
- ABC transportéry biosyntéza genetika metabolismus MeSH
- embryonální vývoj genetika fyziologie MeSH
- exprese genu MeSH
- játra embryologie MeSH
- ledviny embryologie MeSH
- lidé MeSH
- mnohočetná léková rezistence MeSH
- P-glykoproteiny biosyntéza genetika metabolismus MeSH
- střeva embryologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Breast cancer is currently the most common cancer in women worldwide. For this reason, new biomarkers for better predicting response to treatment are needed. CD40, described as expressed in haematological and epithelial tumors, is linked to apoptosis and offers promise as a new predictive/ prognostic marker. We evaluated CD40 expression in formalin-fixed, paraffin-embedded samples from 181 breast carcinomas using immunohistochemical staining with CD40 antibody. Samples were divided according to hormone (oestrogen receptor /ER/, progesterone receptor /PR/) and her-2/neu status into groups: 1.Luminal A (ER+PR+her-2/neu-), 2. Luminal B (ER+PR+her-2/neu+), 3.Triple-negative (ER-PR-her-2/neu-) and 4. Her-2/neu (ER-PR-her-2/neu+). The results of CD40 staining were correlated with clinicopathological data. CD40 was found to be expressed in membrane, cytoplasm and nucleus. Normal ducts expressed cytoplasmic CD40 in 30% of cases, in breast tumor ducts in 53% of cases. CD40 was evaluated as an independent marker and significant positive correlation was found with Bcl-2 (p =0.002), early stage (p =0.016) and preoperative chemotherapy (p =0.043). There was higher overall survival for patients with cytoplasmic CD40 expression (0.05). Differences in expression of cytoplasmic CD40 between groups with different hormonal and her-2/neu status were statistically highly significant (p=0.00003). In groups with different hormonal status, a positive statistical correlation was found for the luminal A group with relapse (p=0.024) and stage (p=0.006). No correlation was found with age, disease onset, family history of cancer/ breast cancer, patient history, hormonal replacement therapy, menopausal status at onset of disease, adjuvant chemotherapeutic treatment or disease free survival. Nuclear expression of CD40 was found to be unrelated to any clinicopathological data. However, there was higher ratio of positive cases in cancer cases (83%) than in normal tissue (30%). In conclusion, cytoplasmic expression of CD40 is related to factors connected to better prognosis and suggest that CD40 may have potential as a new prognostic factor in breast cancer.
- MeSH
- antigeny CD40 analýza fyziologie MeSH
- dospělí MeSH
- imunohistochemie MeSH
- lidé středního věku MeSH
- lidé MeSH
- nádory prsu chemie mortalita patologie MeSH
- prognóza MeSH
- receptor erbB-2 analýza MeSH
- receptory pro estrogeny analýza MeSH
- receptory progesteronu analýza MeSH
- senioři MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Publikační typ
- abstrakt z konference MeSH
