Inactivations of DNA repair genes, O 6 -methylguanine-DNA methyltransferase (MGMT) and hMLH1, by promoter hypermethylation have been reported in several types of primary human neoplasia. This epigenetic inactivation mechanism remains elusive in hepatocellular carcinoma (HCC). To investigate the relation between the expression of MGMT and hMLH1 and the CpG methylation within their promoters in HCCs with or without hepatitis viral infection, we performed immunohistochemistry and urea/bisulphite sequencing on 46 HCCs, corresponding noncancerous tissues, and 20 normal liver tissues. MGMT-and hMLH1-negative HCCs were 60.9% (28 out of 46) and 21.8% (10 out of 46), respectively. HCCs lacking both proteins were 10.9% (five out of 46). The frequency and extent of CpG methylation in the MGMT promoter increased along with hepatitis viral infection and pathological progression. MGMT-negative tumours showed very frequent and widespread methylation in the promoter compared with MGMT-positive tumours. Half of the hMLH1-negative HCCs showed promoter hypermethylation. These data suggested that MGMT gene silencing in a subset of HCCs was likely caused by epigenetic alteration, such as promoter hypermethylation, and that the promoter hypermethylation silenced the hMLH1 gene in half of the hMLH1-negative tumours. A correlation between the promoter methylation status and viral infection, although it was weak, intimated that hepatitis viral infections could play a role in the CpG methylation of the MGMT promoter.

Combined MGMT and MMR is a possible prognostic marker that probably reflects an accumulation of genetic mutations.

A 22-year-old woman, gravida 2, para 0, showed massive vaginal bleeding and was admitted to our institution. She had persistent vaginal bleeding for 4 weeks after a secondary artificial abortion at 14 weeks' gestation. When she was presented to our hospital, evaluation included negative urine hCG, and hemoglobin of 10.7 g/dl. Vaginal examination showed no uterine enlargement and no adnexal mass, but vaginal bleeding and some bloody coagula was recognized. Transvaginal ultrasound showed multiple tubular anechoic spaces without mass effect in the myometrium from the left anterior wall to the fundus. As dysfunction of uterine contraction due to retained products of conception, or trauma following artificial abortion was suspected, she was administered 0.2 mg of intramuscular methylergometrine maleate and 0.5 mg/day of oral methylergometrine maleate for 5 days. Vaginal bleeding decreased soon after the intramuscular injection, and she was discharged the next day with no vaginal bleeding. One week later, she was admitted again to our hospital with massive vaginal bleeding. Her hemoglobin was 6.9 g/dl. She was given only 0.5 mg/day of methylergometrine maleate orally for 7 days, which stopped the vaginal bleeding immediately. Her hemoglobin value subsequently rose by oral administration of iron alone. Percutaneous transfemoral angiography showed a 3¿2 cm hypervascular mass which looked like nidus in the left uterine wall (Fig. 1), and Color Doppler ultrasound revealed a mosaic pattern in the same area of the uterine wall, which was compatible with uterine AVM. Approximately one month later, angiography was performed again for embolization, but the procedure was not carried out because of an obvious reduction in the size of the lesion. Color Doppler ultrasonography also demonstrated the decreased size of the mosaic pattern area. After discharge, follow-up Color Doppler examinations showed no signs of abnormal findings, nor any abnormal bleeding. She conceived 8 months after her previous pregnancy. Her pregnancy progressed quite normally, Abbreviation: AVM: arteriovenous malformation.C Acta Obstet Gynecol Scand 80 (2001) and ultrasound evaluation showed normal fetal growth. At 38 weeks' gestation, a normal male infant weighing 3504 g was born by cesarean section. During the operation, no abnormality was found in the uterine myometrium by ultrasound or macroscopy. DiscussionUterine AVM is a very rare condition and hysterectomy or embolization has been applied in its treatment. Conservative management, such as embolization, is preferable for the preservation of reproductive capability. To our knowledge, there have been ten reported cases of pregnancies after embolization of uterine AVM and one case of the noninvasive management of uterine AVM with methylergometrine maleate in 1999. We report here on a case of successful management of uterine AVM with methylergometrine maleate which was followed by full term pregnancy.Uterine AVMs are either congenital or acquired. Congenital uterine AVMs are considered to be the result of ...

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Perivascular epithelioid cell tumor (PEComas), other than angiomyolipoma, clear cell 'sugar' tumor of the lung, and lymphangioleiomyomatosis, is an uncommon mesenchymal neoplasm that arises in the soft tissue and visceral organs. We report herein two cases of sclerosing PEComa; a distinctive variant of PEComa, which is characterized by extensive stromal hyalinization, occurring in the uterus and broad ligament. The patients were 34-and 51-year-old females with no family history of tuberous sclerosis complex. Macroscopically, the tumors had white to gray cut surfaces and were microscopically composed of predominantly spindle-to polygon-shaped cells with clear to slightly eosinophilic cytoplasm and pleomorphic nuclei focally arranged in a perivascular pattern, accompanied by marked stromal hyalinization. These tumor cells were immunohistochemically positive for HMB45 and a-smooth muscle actin. Although this variant of PEComa is very rare, this entity should be considered as a potential primary neoplasm of the female genital organs.