Evaluating the predictive value of fetal Doppler indices and neonatal outcome in late-onset preeclampsia with severe features: a cross-sectional study in a resource-limited setting.

BACKGROUND: Preeclampsia constitutes a major health problem with substantial maternal and perinatal morbidity and mortality. The aim of this study was to detect the diagnostic efficacy of fetal Doppler in predicting adverse outcomes in severe late onset preeclampsia (LOP). METHODS: A prospective study was conducted among childbearing women who presented with severe LOP and matched controls. Umbilical artery (UA) and middle cerebral artery (MCA) Doppler indices including pulsatility index (PI), resistance index (RI), systolic/diastolic ratio (S/D) and cerebroplacental ratio (CPR) were measured. RESULTS: All UA indices were significantly higher in the case group compared to the controls (p < 0.001). UA PI and RI were significantly correlated with all neonatal adverse outcomes except cord pH status (p < 0.05). Abnormal CPR was the most sensitive index that positively correlated with intrauterine growth retardation (IUGR), low 5- minute Apgar score and neonatal intensive care unit admission (79, 72.8 and 73.3%, respectively). In the same context, Abnormal UA PI and RI represented the most specific tool for predicting IUGR, low 1- and 5- minutes Apgar score with positive predictive values were 52, 87 and 57%, respectively. CONCLUSION: In severe LOP, UA Doppler remains the preferential indicator for adverse birth outcomes with CPR is the best index that could be solely used for predicting such outcome.

Concordance Between FISH Analysis of Her-2/Neu Gene in Breast Duct Carcinoma and Corresponding Axillary Nodal Metastases: Egyptian National Cancer Institute Experience.

BACKGROUND: Breast cancer is a major health problem in Egypt. Her-2/Neu gene is routinely assessed for all breast cancer patients primarily by immunohistochemistry. At National Cancer Institute (NCI), Cairo University, Flourescence In Situ hybridization (FISH) analysis of Her-2/Neu gene is carried out for Her-2/Neu score 2 and for some cases of score 3 (particularly those assessed outside NCI). The test is performed essentially on the primary tumor. However, some situations require testing on corresponding lymph node metastases. There is a debate about the concordance between Her-2/Neu status in the primary tumor and synchronous lymph node metastases in various studies. AIM OF THE STUDY: The aim of this study was to test for the concordance between Her-2/Neu status in the primary breast tumor and corresponding axillary nodal metastases. MATERIALS AND METHODS: This is a retrospective study in which FISH analysis of Her-2/Neu was carried out simultaneously on archived material of 50 cases previously diagnosed as invasive duct carcinoma and the corresponding nodal metastases from the Pathology Department, NCI. RESULTS: There was complete concordance between Her-2 status in the primary tumor and the corresponding axillary lymph node metastatic deposits in which Her-2 was amplified in 44% of the studied cohort of Egyptian patients. CONCLUSIONS: Her-2/Neu gene assessed by FISH analysis on synchronous lymph node metastases is strongly correlated with the primary tumor. Hence, it is justified to carry out the Her-2/Neu test on synchronous lymph nodes to decide on whether to carry out anti-Her-2/Neu target therapy. Further studies on other metastatic sites is recommended.

Fibrosis in Chronic Hepatitis C: Correlation between Immunohistochemically-Assessed Virus Load with Steatosis and Cellular Iron Content.

AIM: We aimed study impact of hepatocytic viral load, steatosis, and iron load on fibrosis in chronic hepatitis C and role of VEGF and VEGFR overexpression in cirrhotic cases in evolving HCC. MATERIAL AND METHODS: Total of 120 cases were included from TBRI and Beaujon Hospital as chronic hepatitis C (CHC), post-hepatitis C cirrhosis, and HCC. Cases of CHC were stained for Sirius red, Prussian blue and immunohistochemically (IHC) for HCV-NS3/NS4. HCC were stained IHC for VEGF and by FISH. RESULTS: Stage of fibrosis was significantly correlated with inflammation in CHC (P < 0.01). Noticed iron load did not correlate with fibrosis. Steatosis was associated with higher inflammation and fibrosis. The cellular viral load did not correlate with inflammation, steatosis or fibrosis. VEGF by IHC was significantly higher in cases of HCC when compared to cirrhotic group (P < 0.001). Amplification of VEGFR2 was confirmed in 40% of cases of HCC. Scoring of VEGF by IHC was the good indicator of VEGFR2 amplification by FISH (P < 0.005). CONCLUSION: Grade of inflammation is the factor affecting fibrosis in CHC. The degree of liver damage is not related to cellular viral load or iron load. Steatosis is associated with higher inflammation and fibrosis. VEGF by IHC is correlated with overexpression of VEGFR2 by FISH.

The clinical significance of HER2 protein amplification/expression in urinary bladder lesion.

OBJECTIVE: To evaluate HER2 oncoprotein expression by both immunohistochemical (IHC) staining and fluorescence in situ hybridisation (FISH) in different benign and malignant bladder lesions, and the effect of bilharzial infestation on this expression. PATIENTS AND METHODS: In a prospective controlled study, 72 patients were classified into a control group, and groups with cystitis, urothelial carcinoma, and squamous cell carcinoma (SCC). HER2 was detected using standard IHC staining and FISH in all groups. The correlation of HER2 expression with tumour type, stage and grade in relation to normal urothelium and cystitis was assessed. The effect of schistosomal infestation was evaluated. RESULTS: HER2 expression was statistically significantly higher in patients with malignant lesions than in the other groups, and in high-stage and -grade tumours than in low-stage and -grade tumours. The use of FISH increased the detection of HER2-positive tumours. Schistosomal infestation did not affect HER2 expression in patients with transitional cell carcinoma. CONCLUSION: High-stage and -grade bladder malignancies expressed HER2 much more than did benign lesions. FISH is more sensitive for detecting HER2 expression. The treatment of HER2-positive tumours might benefit from novel targeted-treatment protocols.

Superiority of fluorescent in situ hybridization over immunohistochemistry in detection of HER2 gene in carcinoma of the urinary bladder associated with and without schistosomiasis.

HER2 is an oncogene encoding a type 1 tyrosine kinase growth factor receptor and the role of HER2 in the development of numerous types of human cancer is still understood and correlates with clinical outcome, poor prognosis, it is a predictor factor for poor response to chemotherapy. HER2 overexpression is associated with reduced disease free and overall survival. Patients who have HER2 negative expression have a poor prognosis. The aim of the present study is to explore the accuracy of detection of expression of HER2 protein by two different techniques of immunohistochemistry (IHC) and gene amplification by fluorescent in situ hybridization (FISH). The two techniques were applied to sixty two patients that included different cell types of carcinoma of the bladder, benign bilharzial lesions and control. Characteristics of the 62 patients are: 10 chronic cystitis, 19 squamous cell carcinoma (SCC) with schistosomiasis, 33 urothelial carcinoma (UC) schistosomal and non-schistosomal, ten healthy individuals without schistosomiasis served as controls. Gene amplification of HER2 was done using FISH and protein expression of HER2 by IHC. The study was applied on archival data of formalin-fixed paraffin embedded tissues and patient clinical data and follow up for 5 years. Overexpression of HER2 protein was found in 30/52 (57.7%). Fourteen cases had score of 2+, and sixteen cases had score of 3+. Using FISH technique it showed more accurate detection of HER2 gene as those fourteen cases who had score of 2+ had been found to be 5 out of 14 were positive for gene over expression, the other sixteen who had score of 3+ all were positive for gene amplification. HER2 protein and gene was found to be significantly overexpressed in carcinoma of the bladder in both cell types SCC and UC with or without schistosomiasis compared to the benign lesions and control groups (P <0.01) by both techniques. There is significant increase in expression of HER2 protein and gene in SCC compared to UC (P< 0.01). In UC overexpression of HER2 protein and gene was evident in all stages Ta, T1, T2-4. HER2 protein and gene overexpressed in different grades of UC. In SCC HER2 protein and gene had overexpression in different stages and grades.

Prenatal diagnosis of beta-thalassemia in Egypt: implementing accurate high-tech methods did not reflect much on the outcome.

The clinical severity of thalassemia major makes it a priority genetic disease for prevention programs through prenatal diagnosis for carrier couples. Incorporation of automated DNA sequencing that enables the characterization of mutations not detected by other mutation specific detection procedures was a prime goal of this work. Automated DNA sequencing was offered on fetal tissues in 30 pregnancies during the year 2005. The pregnancies were at high risk for homozygosity or compound heterozygosity for beta-thalassemia based on mutation analysis of both parents before prenatal diagnosis. Both parents have beta-thalassemia trait. Fetal samples were collected by chorionic villus sampling (CVS) in the first trimester and by amniocentesis in the second trimester. The point mutations were characterized by PCR (ARMS). The absence of the expected fragment with all the mutant ARMS primers insinuated an uncharacterized DNA segment that was further subjected to direct automated fluorescent DNA sequencing in an attempt to know if the fetus was affected by parents' mutations. If no mutation was detected using the PCR ARMS, the sample was further analyzed using direct automated fluorescent DNA sequencing. The mean gestation when carrying out the invasive procedure was 14 (10 -18) weeks. All mothers had a previous affected pregnancy, and 13 had two or more previous affected pregnancies. Pregnancies were: 8 carrier fetuses (trait) and 22 affected fetuses in which 2 were homozygous and 20 double heterozygous. Fourteen parents of affected fetuses preferred to continue pregnancy and the babies were born as diagnosed. The other 8 parents decided on termination and DNA of the abortuses proved to be as previously diagnosed by DNA sequencing. The use of PCR amplification and direct sequencing have permitted the accurate characterization of unidentified alleles and successfully solved 100% of the examined samples. However, it has resulted in minor changes of the outcome as the majority of couples preferred continuation of pregnancy.

The Role of 2D, 3D ultrasound and color doppler in the diagnosis of benign and malignant endometrial lesions.

Forty eight female patients, 15 in the child-bearing period, 6 pre- and 27 postmenopausal, with ages ranging from 35 to 78 years, presented with abnormal uterine bleeding. They were subjected to 2D, 3D ultrasound and Doppler studies. The combined use of ultrasound and Doppler was highly suggestive in the diagnosis of 19 cases of submucous leiomyoma, 16 cases of endometrial hyperplasia, 9 cases of endometrial carcinoma and 4 cases of endometrial polyp, with overall sensitivity and specificity of 93.75 % and 81.25 % respectively. The diagnosis of 35 cases was established by D&C or hysteroscopy and biopsy. The remaining 8 cases were highly suggestive of submucous leiomyomata by ultrasound and color Doppler; the patients refused invasive procedures and were followed after 6 months with no significant changes. Key Words : 2D, 3D ultrasound - Color doppler - Endometrial lesions.