ADAM12-s in coelomic fluid and maternal serum in early pregnancy

OBJECTIVES: ADAM12-s is a placental protein. In early pregnancy, reduced maternal levels of ADAM12-s have been reported in association with foetal trisomy 21 or 18 and in cases that subsequently develop pre-eclampsia and foetal growth restriction. The aim of this study is to investigate the distribution of ADAM12-s in early pregnancy by comparing its concentration in maternal serum, amniotic fluid and coelomic fluid. METHODS: Coelomic fluid was obtained by coelocentesis from 13 singleton pregnancies with live foetuses at 6.9-9.3 weeks of gestation. Maternal serum was also obtained in all cases and in six cases amniotic fluid was also obtained. The concentration of ADAM12-s was measured by dissociation enhanced lanthanide fluoro-immunoassay. RESULTS: The median concentration of ADAM12-s in maternal serum was 132.7 (range 33.8-254.5) ng/mL and in coelomic fluid it was 10.5 (range 1.3-15.8) ng/mL; there were no detectable levels in five of the six amniotic fluid samples. The concentration of maternal serum ADAM12-s increased significantly with gestation (r = 0.862, p < 0.0001). There was no significant association between coelomic fluid ADAM12-s and either gestation (r = 0.255, p = 0.401) or maternal serum ADAM12-s (r = 0.302, p = 0.316). CONCLUSION: The distribution of ADAM12-s in maternal serum and the early embryonic fluid compartments is consistent with its syncytiotrophoblastic origin.     

Interaction between the polymorphisms of the renin-angiotensin system in preeclampsia

Preeclampsia is considered to be a multifactorial and multisystemic disorder with a genetic predisposition. Alterations in the renin-angiotensin system are considered to play a significant role in the pathogenesis of the disease. In order to investigate the possible association of the three most common polymorphisms of the renin-angiotensin system genes with preeclampsia we have examined 41 women with preeclampsia and 102 normotensive pregnant women. DNA samples were genotyped for the M235T polymorphism of the angiotensinogen gene (AGT), the insertion/deletion (I/D) polymorphism of the angiotensin-converting enzyme gene (ACE) and the A1166C polymorphism of the angiotensin II type 1 receptor gene (AT1R) by PCR. Allele and genotype frequencies of the AGT gene polymorphism differed between the two study groups. The TT genotype of the M235T polymorphism was significantly increased in women who developed preeclampsia (P<0.02). In addition, women with preeclampsia and TT genotype had more frequently the DD genotype or the 1166C allele than the control group showing a significant interaction between the genes. In conclusion, we found an association between the angiotensinogen variant 235T and preeclampsia as well as an interaction between the variant 235T and the two other genes studied.     

The role of HPV DNA testing in the follow-up period after treatment for CIN: a systematic review of the literature

BACKGROUND: There is an emerging interest concerning the role HPV DNA testing in the follow-up period after conservative treatment for cervical intraepithelial neoplasia. METHODS: A MEDLINE and EMBASE search was done (1985 to March 2002), using the keywords HPV/HPV DNA, together with CIN, follow-up, recurrence and LLETZ. References of retrieved articles were also screened. Selection criteria were original published English-language reports of prospective or retrospective studies, including women with an initial diagnosis of cervical intraepithelial neoplasia, who received conservative surgical treatment and were followed with HPV DNA testing in addition to cytology, colposcopy and/or biopsy); the latter methods were used for verification of residual or recurrent disease. RESULTS: There is a marked heterogeneity in the design, population, intervention and follow-up policy across different studies. The sensitivity of HPV DNA testing in detecting treatment failures was quite good in most studies, reaching 100% in four of them, whereas the specificity of the test differed across the studies, ranging from 44% to 95%. Among women in whom the treatment was considered to be successful, 84.2% had a negative postoperative HPV DNA test and 15.8% a positive one. The corresponding rates for cases with treatment failures were 17.2% and 82.8%, respectively. CONCLUSIONs: It seems that a positive HPV test, even in the presence of normal cytology, may pick up early and accurately a treatment failure. Cytology and colposcopy may still be needed in order to rule out false positive and false negative results. MINI-ABSTRACT: A systematic review of studies concerning HPV DNA testing in the follow-up period after conservative treatment for cervical intraepithelial neoplasia indicates that a positive HPV test, even in the presence of normal cytology, may pick up early and accurately a treatment failure. Cytology and colposcopy may still be needed in order to rule out false positive and false negative results.     

Early prenatal diagnosis by celocentesis.

BACKGROUND: Celocentesis is the ultrasound-guided aspiration of fluid from the extra-amniotic cavity at 7-8 weeks of gestation. This paper reports on the clinical application of celocentesis for early prenatal diagnosis. METHODS: Celocentesis was successfully performed in nine pregnancies and 1-2 mL of fluid were obtained after one needle insertion. The indications were prenatal diagnosis of beta-thalassemia or sickle cell disease (n = 6), Marfan syndrome (n = 1) and paternity testing (n = 2). Molecular biological techniques were used to analyze the celomic fluid and this was successfully carried out in all cases. RESULTS: In two cases pregnancy termination was performed at the request of the mother because in one case the fetus was found to have sickle cell anemia and in the second case paternity testing demonstrated that the father was not the woman's husband. In both cases the results were confirmed using the placental samples collected after pregnancy termination. In six of the seven pregnancies with desirable results, amniocentesis was performed at 16 weeks and the results were concordant with those obtained from celocentesis. All pregnancies were uneventful and resulted in the delivery of healthy and appropriately grown babies. CONCLUSION: Celocentesis may be a viable alternative to the currently used tests of chorionic villus sampling and amniocentesis.     

Physiological distribution of placental growth factor and soluble Flt-1 in early pregnancy

OBJECTIVE: To examine the distribution of placental growth factor (PlGF), vascular endothelial growth factor (VEGF) and soluble VEGF receptor-1 (sFlt-1) in maternal and embryonic fluid compartments in early pregnancy. METHOD: The concentrations of PlGF, VEGF and sFlt-1 were measured in coelomic fluid and maternal serum from 16 singleton pregnancies at 7.0-9.3 weeks. In six cases, amniotic fluid was also examined. RESULTS: The median concentration of PlGF was 14.1 (range 8.9-27.6) pg/mL in maternal serum, 13.9 (range 9.5-31.4) pg/mL in coelomic fluid and 8.9 (range 3.9-15.3) pg/mL in amniotic fluid. The concentration of PlGF increased between 7.0 and 9.3 weeks in maternal serum (p = 0.001) and decreased in coelomic and amniotic fluid (p = 0.001). The median concentration of sFlt-1 was 8561 (range 6724-10 673) pg/mL in coelomic fluid, 523 (range 244-986) pg/mL in maternal serum, 30 (range 12-83) pg/mL in amniotic fluid (p = 0.0001), and it did not change significantly with gestation. VEGF was undetectable in most of the samples, and therefore, no further analysis was performed. CONCLUSION: PlGF and sFlt-1 are present in the maternal and fetal fluid compartments in very early pregnancy, and their distribution is consistent with their site of production and the local conditions of transport.     

The enigmatic nature of apocrine breast lesions

Epithelial cells of fetal breast glandular structures, at the third trimester of pregnancy (28 weeks), produce GCDFP-15, in the absence of specific apocrine morphology. Apocrine epithelium of the breast may be a normal process of differentiation rather than a result of metaplasia, and it has been demonstrated that it is estrogen-receptor, progesterone-receptor and bcl-2 negative, but androgen-receptor (AR) positive. The significance of AR expression in apocrine epithelium is uncertain. Apocrine epithelium is seen in a wide spectrum of breast entities, ranging from benign lesions to invasive carcinoma. Breast cancer accounts 32% of all cancer cases among women and is the most common type of cancer in women. Little is known about breast carcinogenesis. Widely, it is accepted that breast cancer, like most other type of cancer, is being developed through the accumulation of genetic aberrations. Apocrine epithelium may reflect instability of the breast epithelium, creating an environment favouring further oncogenic alterations. In the last decade, several lines of evidence support the idea that some breast benign epithelial apocrine lesions are clonal lesions and may be considered as truly pre-malignant or precursors of breast carcinoma. Apocrine changes in many cases do not present any diagnostic difficulty; on the other hand, apocrine proliferations with cytologic atypia can be particularly difficult and challenging. The purpose of this study is to collect and highlight the areas of consensus in the literature as well as the controversial areas concerning the apocrine epithelium of the breast.     

Apoptosis in human endometrium and endometriosis

Apoptosis plays a critical role in maintaining tissue homeostasis and represents a normal function to eliminate excess or dysfunctional cells. Accumulated evidence suggests that apoptosis helps to maintain cellular homeostasis during the menstrual cycle by eliminating senescent cells from the functional layer of the uterine endometrium during the late secretory and menstrual phase of the cycle. The BCL-2 family and Fas/FasL system have been extensively studied in human endometrium and endometriotic tissues. Eutopic endometrium from women with endometriosis reportedly has some fundamental differences compared with normal endometrium of women without endometriosis. The differences could contribute to the survival of regurgitating endometrial cells into the peritoneal cavity and the development of endometriosis. One mechanism that recently gained a lot of interest is the finding that apoptosis appeared in eutopic and ectopic endometrium of patients with endometriosis. This study is a current review of the literature focused on the physiological role of apoptosis in normal endometrium and the alterations in regulation of apoptosis in eutopic and ectopic endometrium from women with endometriosis. Similarities in characteristics of endometriosis at a molecular level with gynaecological tumours are also discussed. Finally, the role of apoptosis in the treatment of endometriosis is reviewed to link the basic research findings into clinical applications.