ABSTRACT
BACKGROUND: Tamoxifen has anti-oestrogenic and anti-tumour activity in the breast, but is oestrogenic and carcinogenic in the endometrium. It can induce experimental tumours by both hormonal and DNA-damaging mechanisms, but its carcinogenic mode of action in human endometrium remains unclear. METHODS: We investigated whether an epigenetic mechanism, involving promoter hypermethylation of the gene for the DNA repair enzyme MGMT (O6-methylguanine DNA methyltransferase), was associated with K-RAS, TP53 and PTEN mutations in endometrial tumours from women treated with tamoxifen (TAM, n=30) or unexposed to the drug (EC, n=38). RESULTS: There were significant (P<0.05) differences in tumour grade between the TAM and EC groups, with more favourable morphology in the latter. K-RAS mutations, predominantly G>A, occurred in small numbers in both groups. TP53 mutations were of mainly A>G, C>T and indel modifications in both groups, but more frequent in TAM cases. PTEN mutations dominated in EC tumours and were of the type that has large impact on protein function, such as indel or nonsense mutations. These observations alongside the mutational spectrum in PTEN suggest that the malignancies arise from different backgrounds, hence pointing to an effect of tamoxifen. Both groups displayed MGMT promoter hypermethylation. This coincided with mutations more frequently in the TAM (78%) than in the EC (50%) group, even though there were significantly (P<0.05) fewer mutations and methylations in TAM cases. CONCLUSIONS: Although the difference in coincidence did not reach significance with the current sample size, the findings suggest that epigenetic processes may play a role in the way tamoxifen induces endometrial cancer.
Subject(s)
DNA Methylation , DNA Modification Methylases/genetics , DNA Repair Enzymes/genetics , Endometrial Neoplasms/chemically induced , Endometrial Neoplasms/genetics , Endometrium/drug effects , Selective Estrogen Receptor Modulators/adverse effects , Tamoxifen/adverse effects , Tumor Suppressor Proteins/genetics , Aged , Base Sequence , Endometrium/pathology , Epigenesis, Genetic , Estrogen Antagonists/therapeutic use , Female , Gene Expression Regulation, Neoplastic , Humans , Mutation , PTEN Phosphohydrolase/genetics , Promoter Regions, Genetic , Proto-Oncogene Proteins p21(ras)/genetics , Selective Estrogen Receptor Modulators/therapeutic use , Sequence Analysis, DNA , Tamoxifen/therapeutic use , Tumor Suppressor Protein p53/geneticsABSTRACT
OBJECTIVE: To report a case of Caesarean scar endometriosis presenting as acute abdomen and a review of literature. DESIGN: Case report and literature review. PATIENT: A 27-year-old woman presented in Accident and Emergency Department with pain and lump near left edge of pfannenstiel incision scar. INTERVENTION: After initial investigations the patient underwent examination under anesthesia. MAIN OUTCOME MEASURE: Excision of a tumour-like mass adherent to the skin and the surrounding subcutaneous tissue. The mass was dissected free from the surrounding fat tissue and excised with clear margins. RESULT: Histology of the mass confirmed endometriosis in tumour and showed a 2 cm fibrotic nodule within. CONCLUSION: In light of increasing rate of caesarean section, it is important to emphasize the early diagnosis as well as optimum management of scar endometrioma. Many recommendations have been given to modify practices at caesarean section to prevent transplantation of decidual endometrial tissue in the abdominal scar but without any published randomised trials.