Biomedical subjects
Publications and source records attributed to Mark R J Lansdown.
A comparative review of changing patterns between 1997 and 2002 of who performs appendicectomy and a snapshot of the surgical approaches in use. It also indicates the stage at which competency in appendicectomy may be achieved by contemporary trainees in surgery and anaesthesia.
Oestrogen receptor (ER) alpha is a well established prognostic marker in breast cancer, and all patients who are ER alpha positive receive tamoxifen as adjuvant endocrine therapy. Although ER alpha predicts a favourable disease outcome, the usefulness of ER beta as a clinical prognostic marker remains to be defined. Here, we outline the history of both ERs and discuss the implications ER beta has to patients with breast cancer.
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The majority of breast cancer research is conducted using established breast cancer cell lines as in vitro models. An alternative is to use cultures established from primary breast tumours. Here, we discuss the pros and cons of using both of these models in translational breast cancer research.
To gain insights into the possible role of oestrogen receptor (ER) beta in breast carcinogenesis, immunohistochemical analysis of ER beta was performed on 512 breast specimens encompassing normal (n = 138), pure ductal carcinoma in situ (n = 16), invasive cancers (n = 319), lymph node metastases (n = 31), and recurrences (n = 8). Real-time polymerase chain reaction (PCR) was used to investigate the methylation status of the ER beta gene in the ER beta negative breast cancer cell lines SkBr3 and MDA-MB-435. A gradual reduction in, but not a complete loss of, ER beta expression was observed during the transition from normal and pre-invasive lesions to invasive cancers, where ER beta was lost in 21% of cases. This was more pronounced in invasive ductal than in lobular carcinomas, a significantly higher proportion of which were ER beta-positive (74% compared with 91%, respectively, p = 0.0004). Examination of paired primary cancers with their axillary lymph node metastases showed that if ER beta was present in the primary tumour, it persisted in the metastasis. Treatment of ER beta-negative cell lines with DNA methyl transferase inhibitors restored ER beta expression, providing experimental evidence that silencing of ER beta in breast carcinomas could be due to promoter hypermethylation. These results suggest that loss of ER beta expression is one of the hallmarks of breast carcinogenesis and that it may be a reversible process involving methylation.