Vascular endothelial growth factor single nucleotide polymorphisms and haplotypes in pre-eclampsia: A case-control study.

An association between vascular endothelial growth factor (VEGFA) gene variants and altered VEGF secretion and preeclampsia (PE) were described, often with inconclusive findings. An ethnic contribution to the association of VEGFA polymorphisms with PE and its associated features was also suggested. To investigate whether common VEGFA single nucleotide polymorphisms (SNP) are linked with PE and associated features in Tunisian women. A case-control study involving 300 women with PE, and 300 age-matched control women. Genotyping of VEGFA rs833052, rs699947, rs833061, rs1570360, rs2010963, rs25648, rs833068, rs833070, rs3025020, and rs3025039SNPs was done by real-time PCR. Minor allele frequency (MAF) of rs833052, rs699947, rs833061, rs1570360, rs2010963, rs25648, rs833068, rs833070, rs3025020, and rs3025039 VEGFA SNP, were not significantly different between PE cases and control women. In addition, there was lack of association of the genotypes of VEGFA SNPs with PE, irrespective of the genetic model used. Seven-locus (rs699947, rs833061, rs1570360, rs2010963, rs25648, rs833068 and rs833070) haplotype analysis demonstrated positive association of ATGCCAA, ACAGCAG and CCAGCGG, and negative association of CCAGCAA and ATGCCGG haplotypes with PE, all of which except for ACAGCAG remained associated with PE after correcting for multiple comparisons. Increased and reduced PE severity was associated with ATGCCAA, and with ATGCCGG and CCAGCAA haplotypes, respectively. Furthermore, carriage of CCGGTAG haplotype was associated with reduced risk of PE. Our study suggests that VEGFA haplotypes, more so than individual SNPs, play a role in PE pathogenesis in Tunisian women. These findings need confirmation in other ethnic populations.

C3F gene mutation is involved in the susceptibility to pre-eclampsia.

OBJECTIVE: The aim of this study was to analyze the functional polymorphism of exon 3 of the gene of complement component C3 (rs 2230199) to identify the potential involvement of the mutated gene C3F in the genesis of pre-eclampsia. MATERIEL AND METHODS: It is a comparative case-control study conducted in the university center of maternity and neonatology of Monastir with collaboration of high institute of biotechnology (Tunisia) on a period of 2 years. Two hundred and fifty patients and 96 newborns divided into pre-eclampsia group (150 parturients with pre-eclampsia and 48 newborns) and control group (100 parturients with normal pregnancy and their 48 infants) are taken. Each patient and control were sampled for the phenotypic study and the molecular analysis. The ARMS-PCR (amplification refractory mutation system) was the standard procedure in our study. A simple observation let to distinguish three cases of genotypes: SS, FF and SF. RESULTS: In the control group, 56% of parturients had the genotype SS, 38%, the genotype SF and 6%, FF genotype. In the pre-eclamptic population, SS, SF, and FF genotypes were determined, respectively, 40, 45.30 and 14.60% of the patients. There is a sharp increase in the frequency of the FF genotype in pre-eclamptic patients compared to controls (14.60 vs. 6%). The difference was statistically significant (p = 0.01). The frequencies of C3S and alleles C3F determined in controls (respectively, 74 and 26%) were different from those identified in pre-eclamptic patients (respectively, 62.60 and 37.30%). This difference was statistically significant (p = 0.005). The C3S and C3F allele frequencies determined in control newborns (respectively, 83.33 and 16.66%) were slightly different from those identified in newborn issued from pre-eclamptic patients (respectively, 80.2 and 19.79%), but the difference was not statistically significant (p = 0.67). CONCLUSION: The gene polymorphism of complement component C3 was significantly associated with the onset of pre-eclampsia. These results should be confirmed by other studies looking at larger scale to consider this gene as a new biomarker with predictive potential therapeutic consequences.

Unusual gestational choriocarcinoma arising in an interstitial pregnancy.

INTRODUCTION: Choriocarcinoma is a highly malignant trophoblastic neoplasm. Its association with ectopic pregnancy is very rare and usually with aggressive behavior. PRESENTATION OF CASE: We report a new case arising in an interstitial pregnancy occurring in a 46-year-old woman. The patient was admitted for severe pelvic pain and abundant metrorrhagia. One month ago, she had had a laparoscopic resection of an interstitial pregnancy subsequent to failure of chemotherapy by methotrexate. The raise of serum ßhCG level and the hyperechoic intrauterine mass were in favor of gestational trophoblastic disease. Urgent laparotomy was performed for circulatory collapse. Hysterectomy was done. Histological examination revealed a choriocarcinoma. The patient underwent chemotherapy. Two years later, neither metastasis nor recurrence was detected. DISCUSSION: Clinical diagnosis of primary interstitial choriocarcinoma is difficult, since it is rare and manifesting by non-specific abnormal vaginal bleeding. Imaging findings are also not helpful in ectopic location. The frequency of metastasis is related to the delayed diagnosis. Serial measurement of ßhCG level was the most useful marker of diagnosis and follow up. Histopathological examination remains the only tool of the precise diagnosis. Choriocarcinoma has a very good prognosis even in advanced stages, since it is very chemosensitive. CONCLUSION: The current trend of the treatment of ectopic pregnancy by conservative surgery requires adequate monitoring of ßhCG and careful examination of pathologic specimens to avoid misdiagnosis of ectopic gestational trophoblastic disease.

Ewing's Sarcoma: An Uncommon Breast Tumor.

Ewing's sarcoma/primitive neuroectodermal tumors (EWS/PNET) are rare malignant and aggressive tumors, usually seen in the trunk and lower limbs of children and young adults. They are uncommon in the breast. We report a case of a 43-year-old woman who developed a painless breast mass. An initial core needle biopsy concluded to a fibrocystic dystrophy contrasting with a rapidly growing mass; thus a large lumpectomy was done. Diagnosis of primary PNET of the breast was established, based on both histopathological examination and immunohistochemical findings. Surgical margins were positive, therefore, left modified radical mastectomy with axillary lymph nodes dissection was performed. The patient was given 6 cycles of adjuvant chemotherapy containing cyclophosphamide, adriamycin and vincristine. Twenty months later, she is in life without recurrence or metastasis. EWS/PNET may impose a diagnostic challenge. Indeed, mammography and ultrasonography features are non specific. The histopathological pattern is variable depending on the degree of neuroectodermal differentiation. Immuno-phenotyping is necessary and genetic study is the only confirmatory tool of diagnosis showing a characteristic cytogenetic anomaly; t (11; 22) translocation.

The uterine choriocarcinoma in postmenopausal women: specificities of diagnosis and treatment.

Choriocarcinoma is a gestational trophoblastic tumor that mainly affects women of childbearing age. Cases of choriocarcinoma in postmenopausal women are exceptional. Through an observation and literature review, we propose to study the specific diagnosis and treatment features of this tumor in menopausal women. We report the observation of a pure uterine choriocarcinoma, which occurred in post-menopause. The diagnosis was made on the analysis of surgical specimens confirmed by measurement of hCG. Chemotherapy was started after a total hysterectomy and bilateral salpingo-oophorectomy first. The improvement was dramatic after 3 courses of chemotherapy and the patient is in complete remission after five years of monitoring. The primitive forms of pure choriocarcinoma in postmenopausal women are exceptional. Their etiology is poorly understood and their treatment based on chemotherapy.

Mammary-like adenocarcinoma of the vulva associated to Paget's disease: a case report.

Mammary-like adenocarcinoma of the vulva associated to Paget's disease is exceedingly rare. So, it is very important to perform all the pathological and immunohistochemical investigations to achieve differential diagnosis from both a metastatic lesion from an orthotopic breast cancer and a vulvar adnexal tumor. This report describes a case of vulvar Paget's disease associated with underlying mammary-like adenocarcinoma diagnosed in the Department of Obstetrics and Gynecology of Farhat Hached university hospital of Sousse in Tunisia. We also review previously reported cases of primary breast-like carcinoma of the vulva with or without Paget's disease.