K-ras mutation in the endometrium of tamoxifen-treated breast cancer patients, with a comparison of tamoxifen and toremifene

The putative presence of a mutation in codon 12 of the K-ras gene was investigated in the endometrium of tamoxifen (TAM) and toremifene (TOR)-treated breast cancer patients. DNA was extracted from fresh cytologic samples of the endometrium in 86 TAM and 21 TOR-treated breast cancer patients. Mutations were detected by enriched PCR and an enzyme-linked mini-sequence assay (ELMA). K-ras mutation was found in 35 TAM-treated endometrial samples, and in only one TOR-treated endometrium (P<0.003). In 24 premenopausal patients, K-ras mutation was found in seven (43.8%) of 16 patients with less than 47 months of TAM treatment, while none was found in eight patients with more than 48 months of TAM treatment (P<0.03). In 62 postmenopausal-amenorrheic patients, K-ras mutation was found in three (15.8%) of 19 patients with less than 23 months of TAM treatment, while it was found in 16 (61.5%) of 26 patients with 24–47 months of TAM treatment and nine (52.9%) of 17 patients with more than 48 months of TAM treatment (P=0.002). The presence of K-ras mutation is significantly influenced by the duration of TAM treatment and menstrual status of the patients. TOR may have a lower potential genotoxicity than TAM

Angioleiomyoma of the small intestine – a rare cause of gastrointestinal bleeding

<p>Abstract</p> <p>Background</p> <p>Benign tumors are a rare cause of gastrointestinal hemorrhage of which angioleiomyomas constitute a very small minority. They have been reported in literature to present with volvulus, bleeding or intussusceptions.</p> <p>Case presentation</p> <p>An interesting case of a patient presenting with gastrointestinal bleeding from an underlying angioleiomyoma is discussed along with its management options.</p> <p>Conclusion</p> <p>Angioleiomyoma though rare can be managed successfully by surgical and/or minimally invasive endovascular procedures.</p

An unusual location of retroperitoneal epidermoid cyst in a child: case report and a review of the literature

We report the case of a 4-year-old girl presenting with the retroperitoneal epidermoid cyst. The lesion presented as an intra-abdominal cyst on physical examination and was followed up with more specific investigations by ultrasound and computed tomographic scanning. The final diagnosis was obtained only after laparotomy where the cystic mass was completely excised and pathological examination was done. The patient is well at 3-year follow-up. epidermoid cyst of the reteroperitoneal space, although rare, should be considered in the differential diagnosis of incidentally discovered intra-abdominal cysts during investigation of irrelevant illnesses or during routine abdominal ultrasound scan

MGMT promoter hypermethylation and K-RAS, PTEN and TP53 mutations in tamoxifen-exposed and non-exposed endometrial cancer cases

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 (PA, 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

Effect of menopause on hormonal receptors in ampullae of the fallopian tube with a special reference to the p53 signature

Rie Urabe,1 Toru Hachisuga,1 Taeko Ueda,1 Toshinori Kawagoe,1 Tomoko Kurita,1 Seiji Kagami,1 Masanori Hisaoka,2 Yoshihisa Fujino3 1Department of Obstetrics and Gynecology, 2Department of Pathology and Oncology, 3Department of Preventive Medicine and Community Health, School of Medicine, University of Occupational and Environmental Health, Iseigaoka, Yahatanishi-ku, Kitakyushu, Japan Objectives: Age-related changes in the expression of hormonal receptors have not been well examined in the fallopian tube (FT). We herein report the effect of menopause on the hormone receptors in ampullae of the FTs (AFTs), in comparison with cortical inclusion cysts (CICs) of the ovary.Methods: A total of 84 AFTs and 16 fimbriae of FTs, which were obtained from 26 premenopausal and 58 postmenopausal women; and 27 postmenopausal CICs were immunohistochemically studied for the expression of p53, Ki-67, estrogen receptor-alpha (ER-&alpha;), and progesterone receptor A (PRA). Apoptotic cells were identified using a TUNEL assay.Results: Postmenopausal AFTs showed a significantly lower labeling index (LI) for Ki-67 (P&lt;0.001), apoptosis (P=0.03), and PRA (P&lt;0.001) than premenopausal AFTs. No significant correlation with immunohistochemical markers was found in premenopausal AFTs, but the LI for PRA was positively correlated with that for Ki-67 (P=0.004) and inversely with that for p53 (P=0.023) in postmenopausal AFTs. The expression of immunohistochemical markers was closely correlated between ampullae and fimbriae of the FT. The p53 signature (p53S) was detected in five postmenopausal AFTs (mean age: 70.2 years) and was not detected in any CICs. The immunohistochemical profile of p53S was low expression of Ki-67, apoptosis, and PRA, and high expression of ER-&alpha;. The expression of PRA in CICs was significantly higher than that in AFTs (P=0.001).Conclusion: The expression of PRA was significantly lower in postmenopausal AFTs than in premenopausal AFTs, whereas the expression of PRA was well preserved in postmenopausal CICs. Keywords: fallopian tube, progesterone receptor, estrogen receptor, p53 signature, apoptosi