TWIST1 Gene Expression as a Biomarker for Predicting Primary Doxorubicin Resistance in Breast Cancer.

Doxorubicin is one of the most commonly used chemotherapeutic agents for adjuvant chemotherapy of breast cancer. In the studies focused on finding biomarkers to predict the response of the patients and tumors to the drugs used, the Twist transcription factor has been suggested as a candidate biomarker for predicting chemo-resistance of breast tumors. In this study, we aimed to investigate the relationship between TWIST transcription factor expression and the effectiveness of doxorubicin treatment on directly taken primary tumor samples from chemotherapy-naive breast cancer patients. Twenty-six primary breast tumor samples taken from 26 different breast cancer patients were included in this study. Adenosine triphosphate tumor chemo-sensitivity assay (ATP-TCA) has been used to determine tumor response to doxorubicin and real-time reverse-transcription polymerase chain reaction (RT-PCR) was used for analyzing the TWIST1 gene expression of tumors. There was a significant difference in TWIST gene expression between responder and non responder tumors (p <0.05). The TWIST gene expression of the drug-resistant group was higher than the responsive group. This difference was not dependent on the histopathological features of tumors. In conclusion, compatible with earlier studies that have been performed with cell lines, the current study supports the role of higher TWIST gene expression as a biomarker for predicting the response of breast tumors to chemo-therapeutic agent doxorubicin.

Peripheral primitive neuroectodermal tumor (PNET) of the vulva: a case report.

INTRODUCTION: Ewing's sarcoma/peripheral primitive neuroectodermal tumor (ES-PNET) is a high-grade malignant neoplasm that often develops in the skeletal system. Primary extraskeletal ES-PNET is an uncommon condition that rarely affects the female genital tract. Tumors in the ovary, cervix, and uterine corpus and vulva are occasionally reported. Reports on the Ewing family of tumors involving the vulva are extremely rare in the relevant literature. Only a few cases of vulvar ES-PNET have so far been reported. CASE PRESENTATION: A 14-year-old adolescent girl presented to the clinic with a 4-month history of a left vulvar mass. The mass was excised under general anesthesia, and re-resection was performed three weeks later to obtain negative microscopic margins. The patient received chemotherapy and radiotherapy; however, she died of pulmonary metastasis within nine months of the initial surgery. CONCLUSION: In summary, we describe a rare case of vulvar ES-PNET with distinct rosette-like structures in a 14-year-old adolescent girl with a very poor prognosis.

Lobular carcinoma of the breast metastasizing to leiomyoma in a patient under letrozole treatment.

Metastasis of extragenital neoplasms to the uterus is extremely rare. Lobular breast cancers metastasize to the uterus more than ductal carcinomas, but they metastasize as tiny nodules that can be missed with the standard diagnostic workup. Uterine involvement by a metastatic tumor is usually a manifestation of end-stage disease; patients are reported to die within weeks to months. Therefore surgery is not recommended. Here we report a case of lobular breast cancer metastasizing to a leiomyoma in a patient using letrozole. Our patient was submitted to surgery because the leiomyoma had grown to the level of the xiphoid process. She is alive one year after the operation. In conclusion growth of leiomyomas under aromatase inhibitors should be considered as a sign of metastases and surgery can be planned in selected cases.

Postoperative radiotherapy in the treatment of uterine sarcomas: long-term results and analysis of prognostic factors.

PURPOSE: To evaluate the role of postoperative radiotherapy (RT) in local control and survival and to identify treatment-related prognostic factors in uterine sarcomas. METHODS: Sixty patients with uterine sarcomas treated with postoperative RT were retrospectively analyzed. Median age was 49.5 years (range 24-78). The stage distribution was as follows: stage I: 60%, II: 11.7%, and III: 28.3%. All patients were treated with pelvic irradiation (dose range 45.6-54.6 Gy). Pelvic control (PC), distant metastasis-free survival (DMFS), disease-free survival (DFS), and overall survival (OS) were calculated. Age, stage, histology, tumor size, type of surgery, residual disease, time interval between surgery and RT were selected as possible prognostic factors for PC and OS. Age, total treatment time, pelvic dose, dose per fraction, and acute side effects were analyzed as probable prognostic factors for late complications. RESULTS: Median follow-up was 84 months. The 10-year PC, DMFS, DFS and OS rates were 84, 67.3, 64 and 61.5%, respectively. Univariate analysis showed that age, residual disease, type of surgery and stage were significant factors for PC; residual disease, type of surgery and stage were significant factors for DMFS; stage was found as the only significant factor for DFS and OS. Total treatment time, pelvic dose, dose per fraction, and acute side effects were significant factors for late complications. CONCLUSION: Although our results suggest improved PC, the role of postoperative RT should be tested in prospective randomized trials.

Lymphangioma of the ovary: a case report and review of the literature.

Lymphangioma of the ovary is a very rare tumor which is usually silent and identified incidentally at operation or autopsy. We report on a 61-year-old woman with lymphangioma of the ovary and review the relevant literature. The microscopic examination of the left ovary revealed numerous vascular spaces of different dimensions of which the inner surfaces were lined with flattened endothelial cells with neither cellular atypia nor extraluminal or intraluminal proliferation. There was no evidence of haemorrhage or necrosis. The stroma was formed by fibrocollagenous tissue infiltrated by rare lymphocytes. The cells lining vascular spaces were immunoreactive for CD31 by immunohistochemical staining.

Histomorphology of the placenta and the placental bed of growth restricted foetuses and correlation with the Doppler velocimetries of the uterine and umbilical arteries.

The aim of the present study was to evaluate the histomorphology of the placenta and the placental bed and to correlate this with the Doppler study of the uterine and umbilical arteries of intrauterine growth restricted pregnancies. The study group consisted of 47 women with intrauterine growth restricted foetuses. Twenty-five uneventful pregnancies with appropriate for gestational age foetuses were selected as controls. Doppler studies of umbilical and uterine arteries were performed within the last week before delivery. Placental bed biopsies were obtained at Caesarean section with direct visualization of the placental site. The incidence of pathologic bed biopsies in control, IUGR with normal uterine artery Doppler velocimetry and IUGR with abnormal uterine artery Doppler velocimetry was 0 per cent, 16.6 per cent and 79.3 per cent respectively (P< 0.001). Placentae from IUGR cases with abnormal umbilical artery Doppler velocimetries had a significantly increased number of villous infarcts, cytotrophoblast proliferation and thickening of the villous trophoblastic basal membrane (P=0.001, P=0.038 and P=0.02 respectively). Abnormal placental bed biopsy pathology was significantly associated with abnormal uterine artery velocimetry (OR 33.7, 6.5-173.6; P< 0.001). Abnormal placental pathology was significantly associated with abnormal umbilical artery Doppler velocimetry (OR 21.04, 3.8-115.9;P< 0.001). Women with both abnormal uterine and umbilical artery Doppler velocimetries were delivered earlier and their babies had lower mean birth and placental weight (P< 0.001). In conclusion, placental bed biopsy and placental pathologies are best reflected by abnormal uterine and umbilical artery velocity waveforms, respectively. The most severe clinical outcomes and perinatal mortality are present when both uterine and umbilical districts are altered.

The role of stimulated lipid peroxidation and impaired calcium sequestration in the enhancement of cocaine induced hepatotoxicity by ethanol.

The purpose of this study was to investigate possible mechanism of cocaine-induced hepatotoxicity and its potentiation by ethanol in mice. Ethanol (2 g/kg) and/or cocaine (25 mg/kg) injections were given as binge model (five injections in 3 days). Cocaine administration with or without ethanol caused an increase in lipid peroxidation in liver homogenate and its subcellular fractions. The greatest increases were observed in mitochondrial fraction following cocaine plus ethanol treatment. Also, glutathione (GSH) levels were increased in liver homogenate and its mitochondrial fractions after cocaine and cocaine plus ethanol treatment. Microsomal calcium sequestration was found to decrease in all treatments. These results suggest that increased lipid peroxidation and decreased microsomal calcium sequestration in the liver may play a possible role cocaine-induced hepatotoxicity and its potentiation by ethanol.

A huge abdominal mass mimicking ovarian cancer: p53-negative but aneuploid myxoid leiomyosarcoma of the uterus.

OBJECTIVE: Less than 20 myxoid leiomyosarcoma cases were reported in literature. Since, these tumors are very rare and may exhibit highly malignant behavior despite their low mitotic index, clinical course and optimum type of therapy of myxoid variant of leiomyosarcoma were not well understood. The goal of this report is to contribute the better understanding of this rare type of tumor. METHODS: A 39-year-old woman presented with a huge abdominal cystic mass. Laparotomy was performed and frozen section diagnosis was low-grade uterine leiomyosarcoma. TAH-BSO, omentectomy, pelvic lymph node and peritoneal samplings were carried out. No chemotherapy was performed after surgical therapy. RESULTS: Final histopathological diagnosis was uterine myxoid leiomyosarcoma. The tumor was p53-negative and had aneuploid DNA content. The patient tolerated well the operation and she is alive and free of disease after 24 months of primary surgical treatment. CONCLUSION: Uterine myxoid leiomyosarcoma may present a huge abdominal cystic mass and can be treated successfully with surgery alone.

Apoptosis in the placenta of pregnancies complicated with IUGR.

OBJECTIVE: In this study we have investigated the presence of apoptosis in the placental tissue of pregnancies complicated with intra-uterine growth restriction (IUGR). METHOD: Placental samples were obtained from 22 normal third trimester pregnancies and 20 pregnancies complicated with IUGR. The criteria for fetal growth impairment were clinical evidence of sub-optimal growth, ultrasonographic demonstration of deviation from normal percentiles of growth and birth weight under 10th percentile. Terminal deoxynucleotidyl transferase mediated deoxyuridine triphosphate nick end labelling (TUNEL) staining was used to demonstrate the apoptotic cells in all samples. Student-t, Mann-Withney U-test, Fisher exact test and Spearman correlation were used for statistical analysis. RESULTS: We detected apoptosis in 10 placentas in the study group vs. none in the control group. Placentas from pregnancies complicated with IUGR demonstrated 0.12% (0.1%-0.4%) apoptotic cells. The rate of apoptotic cells in the placenta was significantly higher in pregnancies complicated with IUGR than normal uncomplicated pregnancy (P=0.0019). Apoptosis were more abundant in the trophoblasts, especially cytotrophoblasts, in the placenta. We could not find a correlation between the apoptosis in the placenta of pregnancies complicated with IUGR and birth weight, multi-parity, gestational age, birth weight percentile and mode of delivery (C/S vs. vaginal delivery). CONCLUSION: We believe that the increased number of apoptosis in the placenta of pregnancies complicated with IUGR may have an important compensatory role to transmit nutrition and gas exchange easily to the fetus.

Immunohistochemical analysis of prostate-specific antigen in female breast cancer.

PURPOSE: Prostate-specific antigen (PSA), a glycoprotein initially thought to be produced only by the epithelial cells of the prostate, has recently been found in various tissues and tumors. It has been suggested that the expression of PSA in breast cancer is a good prognostic indicator and correlated with favorable prognosis. However, in recent years opposite results have been reported. In this study, we investigated the immunoreactivity of PSA in female breast cancer to find out any relationship between PSA and prognostic parameters. PATIENTS AND METHODS: Sections of formalin-fixed, paraffin- embedded samples from 109 invasive ductal carcinomas were immunostained for PSA. The staining results were analyzed in relation to age, tumor size, histologic grade, axillary lymph node status and steroid receptors. RESULTS: PSA immunoreactivity was seen in only 11 (10.1%) out of 109 cases. All PSA positive cases were also estrogen (ER) and progesterone receptor (PR) positive. We found a statistically significant correlation between PSA and the expression of steroid receptors, while no correlation was detected with the other factors. CONCLUSION: The detection of PSA, using immunohistochemistry, does not seem to be a reliable prognostic criterion for female breast cancer patients or a marker of tumor origin.

Sclerosing stromal tumor of the ovary: report of three cases.

We present 3 cases displaying sclerosing stromal tumor (SST) of the ovary and describe their immunohistochemical and electron microscopic findings. The patients were 23, 24 and 28-year-old and had an ovarian mass. Histologically, the tumors had the typical appearance of SST of the ovary. A pseudolobular pattern which was composed of cellular areas and less cellular areas was seen on low-power microscopy.

Placental apoptosis and adhesion molecules expression in the placenta and the maternal placental bed of pregnancies complicated by fetal growth restriction with and without pre-eclampsia.

The aim of the study was to examine the expression of adhesion molecules VCAM-1 and ICAM-3 in placental tissue samples and placental bed (maternal decidual tissue) biopsies of pregnancies complicated by pre-eclampsia (PE) and fetal growth restriction (FGR), and to determine whether PE and FGR are associated with an increase in placental apoptosis. We studied placentas and placental bed samples of 49 third trimester pregnancies complicated by FGR (26 with associated PE, 23 without PE) and 25 normotensive healthy pregnant women. Placental apoptosis was assessed by the TUNEL method. Immunohistochemistry was used to assess expression of the VCAM-1 and ICAM-3. There was no significant difference in the staining intensity of VCAM-1 in placentas (p=0.472) and placental bed biopsies (p=0.754) of women delivering appropriate for gestational age and growth restricted fetuses (with and without associated PE). The amount of lymphocytes staining positively with ICAM-3 was significantly higher in both placental and placental bed biopsies of women delivering growth restricted fetuses compared with control pregnancies (p<0.001). Fetal growth restricted pregnancies with associated PE showed higher staining of ICAM-3 in placental compared with placental bed samples (p=0.049). In fetal growth restricted placentas, apoptotic nuclei were more abundant compared with control placentas (p<0.001). Increased expression of ICAM-3 on lymphocyte surface of both maternal and fetal side, suggests lymphocyte overactivation in PE and FGR. Increased placental apoptosis may play an important role in the pathogenesis or sequelae of PE.

Correlation between placental bed biopsy findings, vascular cell adhesion molecule and fibronectin levels in pre-eclampsia.

OBJECTIVE: To determine the correlation between placental bed biopsy findings, and blood levels of the vascular cell adhesion molecule (VCAM-1) and fibronectin in pre-eclampsia/eclampsia, and to evaluate the relationship between these variables and severity of the disease. DESIGN: A prospective case-control study. SETTING: Department of Obstetrics and Gynaecology, Cerrahpasa Medical Faculty, Istanbul. SAMPLE: Thirty-five women with pre-eclampsia/eclampsia were compared with 25 healthy women with uncomplicated pregnancies. Twenty-one placental bed biopsies from pre-eclamptic pregnancies were compared with 17 from normal pregnancies. MAIN OUTCOME MEASURES: Peripheral venous blood levels of VCAM-1 and fibronectin, measured by enzyme-linked immunoassay and radial immune diffusion technique. RESULTS: In pre-eclampsia/eclampsia, blood VCAM-1 and fibronectin levels were higher than in normal pregnancy. Levels of both fibronectin and VCAM-1 correlated significantly with the diastolic blood pressure (r = 0.49 and r = 0.65, P < 0.001). There was also a significant direct linear correlation between plasma fibronectin and VCAM-1 levels (r = 0.57, P < 0.001). Normotensive women all had normal placental bed biopsy findings and the incidence of pathological placental bed biopsy findings increased with the severity of the pre-eclampsia. CONCLUSION: Inadequate trophoblastic invasion of spiral arteries, and elevated levels VCAM-1 and fibronectin were found in women with pre-eclampsia. The magnitude of defective trophoblastic invasion, and blood levels of VCAM-1 and fibronectin correlate with the clinical severity of pre-eclampsia.

DNA ploidy of ectopic pregnancy and first trimester spontaneous abortion investigated by flow cytometry.

BACKGROUND: To compare the success rate of DNA flow cytometry in determining the DNA ploidy status in ectopic pregnancy and first trimester spontaneous abortion. METHODS: Thirteen women with ectopic pregnancy (Group I) and 17 women with first trimester spontaneous abortion (Group II) were included into this study. DNA flow cytometric analysis was performed on all specimens. Aneuploidy was classified according to DNA index. The first trimester spontaneous abortions were also karyotyped after long-term culture of chronic villi. Student-t test and Fisher's exact test were used in statistical comparisons. RESULTS: DNA aneuploidy was found in five women with ectopic pregnancy (38.5%) versus in 12 women with first trimester spontaneous abortion (70.6%), and it was comparable. A triploidy and a tetraploidy were detected in group I. Six tubal ectopic pregnancies were unruptured at laparatomy and four of them had aneuploid DNA content. CONCLUSIONS: We believed that DNA flow cytometry was successful in determining the ploidy status of ectopic pregnancy and first trimester spontaneous abortion. In addition, it was interesting that ectopic pregnancies with aneuploid DNA content tended to be unruptured. However, this suggestion needs to be confirmed by further studies with larger numbers of cases.