Role of Apoptosis in the Development of Uterine Leiomyoma: Analysis of Expression Patterns of Bcl-2 and Bax in Human Leiomyoma Tissue With Clinical Correlations.

To describe gene expression patterns of the apoptotic regulatory genes Bcl and Bax in human uterine leiomyoma tissue. To investigate the relationship between alterations of gene expression patterns and several relevant clinical parameters. We obtained samples from 101 cases undergoing surgery for uterine leiomyoma for gene expression analysis of the Bcl-2 and Bax genes. Gene expression was quantified using RT-PCR technique. In the leiomyoma group, the Bcl-2 gene was significantly overexpressed compared with the control group although there was no such difference in the gene expression of Bax. Gene activity of Bcl-2 positively correlated with the tumor number in individual uterine leiomyoma cases. Although there was no significant correlation between the length of the cumulative lactation period before the development of uterine leiomyoma and Bcl-2 gene expression in the leiomyoma tissue, we observed a trend for a shorter cumulative lactation period to be associated with overexpression of the Bcl-2 gene. Overexpression of the antiapoptotic Bcl-2 gene appeared to be a factor in the development of uterine leiomyoma, whereas gene activity of the proapoptotic Bax gene did not seem to play a role in the process.

Trends in maternal mortality in Hungary between 1978 and 2010.

OBJECTIVE: We evaluated the trends of the last decades in maternal mortality in Hungary and compared Hungarian results with those of other European countries. STUDY DESIGN: Cases of maternal death in Hungary during the study period from calendar year 1978 to 2010 were analyzed in a retrospective manner to characterize mortality distribution and to identify potential clinical or demographic predictors. Data in all cases were extracted both from the national Obstetric Registry operated by the National Institute of Gynecology and Obstetrics, from the Hungarian Central Bureau of Statistics and from the National Public Health and Medical Officer Service. Detailed clinical data were obtained based on obligatory reporting by individual clinical institutions. RESULTS: The annual maternal mortality rate (MMR) was 26.7 per 100,000 live births in the period 1978-1987 and declined significantly to 10.9 per 100,000 live births in the period 1997-2010. In the period 1988-1996 (with missing associated clinical and demographic data) the MMR was 16.4 per 100,000 live births. The proportion of delivery-associated causes of death increased significantly between the two study periods from 49.4% to 62.9% (p<0.05). Among obstetric causes of death, the rate of thromboembolism showed a significant increase, while there was a trend toward a decline in rate of maternal deaths attributable to hemorrhagic shock. Among medical causes of death not directly attributable to obstetric complications, the rate of renal and gastrointestinal etiologies declined significantly throughout the study periods. CONCLUSIONS: We observed a marked decline in maternal mortality during the last few decades in Hungary. Recent changes in mortality distribution highlight current characteristics of pregnancy care in Hungary and may help identify strategies for future improvement.

The role of the alcohol dehydrogenase-1 (ADH1) gene in the pathomechanism of uterine leiomyoma.

OBJECTIVE: To describe alterations of gene expression patterns of the alcohol dehydrogenase-1 (ADH1) gene in human leiomyoma tissue. We correlated changes in ADH1 gene activity with several clinical and demographic variables. STUDY DESIGN: We compared gene expression patterns of ADH1 in leiomyoma tissue samples obtained from 101 hysterectomy cases to 110 cases of hysterectomy performed for non-oncological indications. Gene expression was determined by standard PCR technique. Clinical and epidemiological data were extracted from the computerized database of the 1st Department of Obstetrics and Gynecology of Semmelweis University and from patient questionnaires. RESULTS: Median age in the leiomyoma group was significantly lower than in the control group (47.5 ± 12.1 vs. 54.7 ± 10.2 years). The incidence of uterine leiomyoma was highest (48%) in the 41-50 year age group. In the obstetric history, cumulative gestational age in the leiomyoma group was significantly lower (105.1 ± 8.2 weeks) than in the control group (127.2 ± 9.1 weeks) and cumulative lactation length was also significantly shorter (2.4 ± 1.2 months vs. 5.1 ± 2.2 months). Surgical treatment of the fibroid was myomectomy in 39.6% of the cases and hysterectomy in 60.4%. The ADH1 gene was significantly underexpressed in the leiomyoma group compared to the control group. There was no significant association between ADH1 gene expression and family history. Within the leiomyoma group, there was no significant difference in ADH1 gene expression between subgroups of cases with different number of fibroid tumors found in the hysterectomy sample, but individual tumor number did correlate with the degree of underexpression of the ADH1 gene. There was no significant association between ADH1 gene expression and cumulative history of lactation. CONCLUSIONS: Underexpression of the ADH1 gene, which influences the transformation of the extracellular matrix, plays a probable role in the etiology of uterine fibroid. Although significant differences in ADH1 gene activity were not seen, a negative correlation between tumor number and degree of ADH1 underexpression was found. Neither family history nor cumulative lactation length was a significant predictor of uterine leiomyoma.

Gene expression patterns of insulin-like growth factor 2 in human uterine fibroid tissues: a genetic study with clinical correlations.

BACKGROUND/AIMS: We investigated insulin-like growth factor 2 (IGF-2) gene activity in human uterine fibroid tissue. Results of the genetic testing were correlated with clinical data. METHODS: We obtained samples from patients treated for uterine fibroid and from patients undergoing hysterectomy due to other indications (control group). The examined group (with fibroid) contained 101 cases, while the control group was similar with 110 patients. Gene expression values were determined using the standard PCR technique. Clinical data were available from the computer database of the department. RESULTS: IGF-2 gene expression was significantly higher in the fibroid group. There was no correlation between increase in gene activity and the number of tumors. History of previous uterine fibroid did not seem to predict IGF-2 gene activity in the current fibroid tumor tissue. IGF-2 gene expression did not correlate with cumulative duration of lactation following prior pregnancies. CONCLUSION: IGF-2 gene activity is significantly increased in leiomyoma tissue compared to normal myometrium. Familial aggregation of uterine fibroids is not significantly associated with increased IGF-2 gene activity; other genes may have a stronger etiological role. It appears that the genetic factors potentially important in the development of familiar uterine leiomyoma are not related to the IGF-2 gene.