Placental type alkaline phosphatase tissue expression in ovarian serous carcinoma.

OBJECTIVE: To analyze the expression profile of placental type alkaline phosphatase (PLAP), cancer antigen 125 (CA125), and human epididymis protein 4 (HE4) in serous ovarian cancer and to correlate their expression with the tumor aggressiveness and progression. METHODS: Retrospective study considering a tissue microarray of 82 women affected by ovarian serous cancer. Protein expression was assessed by immunohistochemistry on ovarian serous cancer tissue samples. Immunohistochemical staining was semiquantitatively evaluated as H-score. RESULTS: Median H-score values were lower for PLAP, 1 (IQR 0-4) than CA125, 10 (IQR 6-12) or HE4, 8 (IQR 5-12). Even if PLAP was less expressed in the cells of serous ovarian cancer than CA125 or HE4 it was relatively more expressed in the fourth quartile of its H-score distribution among cases with low CA125 or HE4 expression. Furthermore, PLAP and HE4 high expression resulted to be significantly correlated with a better prognosis. CONCLUSIONS: PLAP could be an additional marker for early detection of serous ovarian carcinoma, together with the established CA125 and HE4. In addition, PLAP expression is correlated with prognosis, giving, in this way, an additional tool for improving treatment approach.

Mismatch repair system in endometriotic tissue and eutopic endometrium of unaffected women.

OBJECTIVE: To test the immunohistochemical staining pattern of some mismatch repair (MMR) system proteins in endometriotic tissue (ET) and eutopic endometrium. METHODS: This was a retrospective study conducted at the Pathology and Obstetrics and Gynecology Departments of the Udine University Hospital. We analyzed 528 samples obtained from 246 patients affected by endometriosis and 71 samples from 71 patients with normal endometrium. A tissue microarray model was used to analyze the immunohistochemical expression of MMR system proteins. RESULTS: Significant loss of MMR proteins was found in the stromal component of ETs. We found MSH2 to be expressed at a higher level than any other MMR system proteins in eutopic endometrium and ETs, to be significantly correlated to Ki-67 expression in both stromal and glandular components of ETs, and to be expressed at a significantly higher level in ETs than in eutopic endometrium. When considering the subgroup of endometriosis with high recurrence rate and glandular cytoplasmic staining for aurora A kinase, we found MMR proteins expressed at a significantly higher level in these ETs than in other ETs and eutopic endometrium of unaffected women. CONCLUSIONS: We found significant loss of MMR proteins (known to be associated with microsatellite instability) in the stromal component of ETs. The group of ETs with glandular cytoplasmic staining for aurora A kinase had higher MMR protein expression, suggesting an increased activity of this system. Our result suggests a novel role of increased MSH2 expression in cellular proliferation of endometriosis.

Surgical treatment of ectopic pregnancy associated with predisposing factors of tuboperitoneal infertility.

OBJECTIVE: We sought to study the advantages of laparoscopic conservative treatment and pelvic reproductive surgery in patients with ectopic pregnancy and predisposing factors of tuboperitoneal infertility. MATERIAL AND METHODS: Patients who had undergone laparoscopic treatment for ectopic pregnancy were considered, with factors for tuboperitoneal infertility, while patients who underwent previous salpingectomy or assisted reproductive technology were excluded. The groups treated by salpingotomy (conservative) or salpingectomy (radical) were compared in terms of spontaneous intrauterine pregnancy rate, cumulative one-year pregnancy rate and recurrence of ectopic pregnancy. We considered patients treated with adhesiolysis, fimbrioplasty, and neosalpingostomy for tubal pathology as part of the fertility surgery group. RESULTS: Among 41 considered patients, 21 (51%) underwent conservative laparoscopic management of ectopic pregnancy. Twenty patients (49%) had salpingectomy. Despite the treatment of tuboperitoneal infertility factors in both groups, the pregnancy rate was significantly higher in the conservative group than in the radical one (76% vs 25%, p < 0.05). The overall cumulative rate of ectopic pregnancy recurrence was 22% and no significant difference was found between conservative and radical treatment (p 0.645). CONCLUSIONS: Salpingotomy should be preferred in all patients with ectopic pregnancy associated with factors of tuboperitoneal infertility. Infertility surgery clearly cannot help patients treated with salpingectomy, who obtain lower spontaneous pregnancy rates than those of the conservative group.

Survivin, MMP-2, MT1-MMP, and TIMP-2: their impact on survival, implantation, and proliferation of endometriotic tissues.

In order to study survivin, matrix metalloproteinases (MMP-2), membranous type 1 matrix metalloproteinase (MT1-MMP), and tissue inhibitor metalloproteinase-2 (TIMP-2) expression immunohistochemically in endometriotic tissues and normal endometrium, our retrospective study considered 194 patients affected by endometriosis and 71 patients with normal endometrium. Tissue microarrays were created from paraffin-embedded blocks; immunohistochemistry was used to assess protein expression. In endometriotic tissues, survivin was expressed at a higher level than in normal endometrium; its glandular expression level was higher in non-ovarian than in ovarian endometriotic tissues and lower in stromal components. Endometrial tissues from women without endometriosis and endometriotic tissues had different matrix metalloproteinase expression profiles. MMP-2 and MT1-MMP correlated with TIMP-2 in endometriotic tissues. Furthermore, in endometriotic tissues, expression of survivin, aurora B kinase, and Ki-67 showed a significant positive correlation, which indicates a role in cellular proliferation that could be closely linked to its anti-apoptotic activity in endometriosis development. Our results imply a role for matrix metalloproteinases in endometriosis invasiveness; correlation of their expression with that of TIMP-2 underscores its possible key regulatory role.

Assessment of endometrial volume and vascularization using transvaginal 3D power Doppler angiography in women with postmenopausal bleeding.

OBJECTIVE: To compare the usefulness of 3D power Doppler angiography (3D-PDA) and endometrial thickness measurement by 2D Doppler ultrasound in the distinction of benign from malignant disease in postmenopausal women with abnormal uterine bleeding (AUB) and an endometrial thickness greater than 4.5mm. METHODS: Forty-eight women with AUB and an endometrial thickness greater than 4.5mm on 2D ultrasound underwent 3D-PDA. The endometrium and a 5-mm subendometrial "shell" were evaluated at rotation angles of 9° and 30°. Endometrial volume, vascularity index, flow index, and vascularization flow index were obtained. RESULTS: The histologic findings were normal or benign for 38 women (79%) and malignant for 10 (21%). All vascular indices were significantly higher in the group with malignancies except for the vascularization flow index. There were no differences in the values obtained using the 9° or the 30° angle. Receiver-operating characteristics curves were traced for all indices. The vascularity index had the best area under the curve (0.78), 77.8% sensitivity, and 82.6% specificity. The areas under the curve were smaller for the shell than for the endometrium. CONCLUSION: 3D-PDA was not found better than 2D ultrasound at distinguishing benign from malignant disease in women with AUB and an endometrial thickness greater than 4.5mm.

Determinants of ante-partum depression: a multicenter study.

INTRODUCTION: Ante-partum depression (APD) is usually defined as a non-psychotic depressive episode of mild to moderate severity, beginning in or extending into pregnancy. APD has received less attention than postpartum depression. This is a cross-sectional study carried out in the Obstetrics and Gynaecology (OG) departments of four different general hospitals in Italy. METHODS: Women attending consecutively the OG departments for their first ultrasound examination were asked to fill in the Edinburgh Postnatal Depression Scale (EPDS) in its Italian validated version. We used the total scores of the EPDS as a continuous variable for univariate and linear regression analyses; in accordance with the literature, the item analysis of EPDS was carried out by classifying the sample as women with "no depression" (scores 0-9), "possible depression" (scores 10-12), "probable depression" (scores 13+) and "probable APD" (scores 15+). RESULTS: The number of women recruited was 1,608. The EPDS assessment classified 10.9 % of the women as possibly depressed, 8.3 % as probably depressed and 4.7 % probably affected from an APD. EPDS score distribution was associated with nationality (higher scores for foreigners), cohabitation (higher scores for women living with friends or in a community), occupation (higher scores for housewives), past episodes of depression and use of herbal drugs. Non-depressed women had significantly lower values on all ten items as compared with depressed women, however, the pattern of item distribution on the EPDS scale remained similar across depression severity groups. In all four groups item 4 (anxious depression) attained the highest scores, while item 10 (suicidality) attained the lowest scores.

Expression patterns of Aurora A and B kinases, Ki-67 and the estrogen and progesterone receptors determined using an endometriosis tissue microarray model.

BACKGROUND: The roles of cell proliferation and genomic instability in endometriosis are highly debated aspects of the pathogenesis of this disease. Aurora A and B kinases play different important roles in cell cycle control and genomic instability and have never been studied in endometriosis. The aim of this study was to compare the expression levels of Aurora kinases, Ki-67 and hormone receptor in endometriotic tissue (ET) and normal endometrium. METHODS: We retrospectively analysed 438 samples obtained from 194 patients affected by endometriosis and 28 samples from 28 patients with normal endometrium, which were all collected by the Pathology Department and Gynecologic Clinic of the University Hospital of Udine. A tissue microarray model was constructed to use immunohistochemistry to analyse the expression of Aurora A and B kinases, Ki-67 and the estrogen and progesterone receptors in ET and normal endometrium. RESULTS: Aurora A and B kinases were expressed at a very low level in the majority of endometriosis core biopsies. Aurora A and B kinases, Ki-67 and the estrogen and progesterone receptors were expressed at a higher level in the proliferative endometrium than in the secretory endometrium and in ovarian and non-ovarian ET (P < 0.05). Additionally, Aurora B kinase, Ki-67 and the estrogen and progesterone receptors were more highly expressed in non-ovarian than ovarian ET (P < 0.05). CONCLUSIONS: Considering the low expression levels of Aurora A and B kinases in the majority of endometriosis core biopsies, the growth and survival of endometrial tissue outside the uterus cannot be explained by deregulation of this pathway. The analysed ectopic endometrium protein expression pattern resembled that of the secretory endometrium, and markers of proliferation and hormone receptors were expressed at lower levels in ovarian than in non-ovarian ET. The low level of hormone receptors and the consequent low levels of proliferation markers in ovarian ETs may be due to down-regulation by the ovary's hormone milieu.

A proposal for a new scoring system to evaluate pelvic masses: Pelvic Masses Score (PMS).

OBJECTIVES: Ovarian cancer is the fourth leading cause of death among neoplastic diseases in women. In spite of constant improvement in surgical, chemotherapeutic and immunologic techniques, which can induce long remission periods, the five-year survival rate has not really changed over the past thirty years. We tried to create a sonographic scoring system, called PMS, that could be helpful in diagnosis of pelvic masses. STUDY DESIGN: The three most commonly used and validated indexes--Sassone score, Ovarian Tumor Index (OTI), and Risk of Malignancy Index 3 (RMI3)--were applied to a population of 102 women with adnexal masses. We developed a new scoring system, named Pelvic Masses Score (PMS), that takes into account the ultrasound morphological pattern, the Doppler flowmetry of the pelvic mass, the CA125 serum level and the menopausal status. We then applied this scoring system to a population of 160 women for validation of the score. RESULTS: Statistical analysis of the data obtained from the new scoring system reveals that sensitivity, specificity, positive and negative predictive values (PPV and NPV) are higher than in the case of data separately derived from the Sassone score, OTI index or RMI index. CONCLUSIONS: Our preliminary data showed good results in term of sensitivity, specify and predictive values compared to other old scoring systems. A larger prospective study is required to confirm these preliminary data. The number of cases will be expanded to permit a better evaluation of PMS.

Acute promyelocytic leukemia during pregnancy.

OBJECTIVE: To report our experience about a woman with acute promyelocytic leukemia (APL) during pregnancy. We focus on the obstetric treatment of our patient. DESIGN: Case report. SETTING: University Hospital. PATIENT(S): A 32-year-old-woman, gravida 2, para 1, at the 25th week of pregnancy with a diagnosis of APL. INTERVENTION(S): Multidisciplinary approach to the problem with the aim to ensure a good outcome for both the mother and the baby. MAIN OUTCOME MEASURE(S): Treatment of maternal malignancy and fetal outcome. RESULT(S): At discharge, after 2 months in hospital, the baby had no neurologic or sensitive deficiencies, and his general health was good. The mother is now undergoing the third and last consolidation step with good results, and APL is in remission. CONCLUSION(S): In cases of APL during the second and third trimesters, the modern chemotherapy associated with close monitoring of maternal and fetal well-being could ensure a good outcome for both the mother and the baby.

[Paget disease of the vulva: resolution after local treatment with imiquimod--report of a case and review of the literature]. / Morbus Paget der Vulva: Remission durch Lokalbehandlung mit Imiquimod--Fallbericht und Literaturübersicht.

Paget disease is a rare disorder of the skin of the vulva, comprising less than 1% of vulvar neoplasms. Surgical excision is considered the standard of care. While the invasive variant of Paget disease is rare, frequent local recurrences from non-invasive disease, which are inoperable, constitute a major clinical problem. In this article we report on a 71-year-old patient with recurrent disease treated successfully with imiquimod cream. Symptoms such as local itching subsided shortly after initiation of treatment. Four weeks later, first signs of resolution could be demonstrated colposcopically. Within 8 weeks, complete clinical remission was achieved. Thus, topical imiquimod is not only effective as treatment of vulvar intraepithelial neoplasia, but may also be used for selected patients with recurrent Paget disease as an alternative to repeat surgical interventions.

Primary hyperparathyroidism in pregnancy.

OBJECTIVE: To determine the management of a patient with primary hyperparathyroidism and the obstetric and neonatologic outcome. DESIGN: Case report. SETTING: University hospital of Udine, Italy. PATIENT(S): A 32-year-old black pregnant woman with primary hyperparathyroidism. INTERVENTION(S): Hospitalization with observation, nuclear magnetic resonance of the neck, and right parathyroidectomy of the patient in the 15th week of gestation (WG). Monitoring during pregnancy until the delivery. MAIN OUTCOME MEASURE(S): Intrauterine pregnancy preservation and maternal and fetal morbidity and mortality. RESULT(S): After surgery, laboratory and clinical findings remained constant. The fetus' well-being until the delivery was performed with cardiotocography (CTG) and echographic monitoring. Symmetric intrauterine growth restriction was discovered at 37 WG. Cesarean section was performed at 38 +/- 2 WG owing to the CTG trace. CONCLUSION(S): Nuclear magnetic resonance of the neck in this case was the determining diagnostic exam. Parathyroidectomy, during the second trimester, is the therapeutic gold standard, especially in cases of severe hypercalcemia (>12 mg/dL).

Locally relapsed and metastatic uterine leiomyoma: a case report.

INTRODUCTION: Benign metastasising leiomyoma refers to a type of lesion characterised by leiomyomatous alterations without any indication of malignancy. It presents as either a singular nodule or multiple nodules of proliferating smooth muscle cells and is generally found in the lungs of women who have undergone a hysterectomy. The purpose of this case report is to contribute to the knowledge of this rare disease by presenting evidence and experience of a patient case. In particular, this report seeks to investigate the therapeutic approaches in order to understand whether a standard of care can be prescribed and whether the use of prophylaxis therapy with progesterone as a follow-up to surgery serves as a reasonable treatment in certain cases diagnosed as benign metastasising leiomyoma. CASE PRESENTATION: We present the case of a 52-year-old Caucasian woman who developed a pelvic relapse and a pulmonary localisation of benign metastasising leiomyoma following a hysterectomy for myomatous uterus. CONCLUSION: Our literature review revealed a single case of the use of chemoprophylaxis as treatment of a benign metastasising leiomyoma. The role of chemoprophylaxis in preventing future recurrences remains unclear. The use of progesterone as an adjuvant therapy for benign metastasising leiomyoma could simply be palliative, with associated psychological benefits, or it could be of therapeutic significance.

Intraepithelial G3 adenocarcinoma of the endometrium after tamoxifen treatment.

CASE REPORT: In this paper we describe a case of endometrial carcinoma observed in a post-menopausal patient who was treated with tamoxifen for 5 years after a mastectomy for cancer. She came to our department because of vaginal bleeding 2 years after the end of tamoxifen treatment. TREATMENT: She underwent hysteroscopy and a D and C. A polypoid endometrium completely filled the uterine cavity and was carefully removed by curettage; histology showed a highly undifferentiated neoplasia with a component of serous adenocarcinoma, which was likely to originate from endometrial polyps. OUTCOME: The patient underwent radical hysterectomy, but no residual tumor was found in the uterus or in the tubes, ovary, or pelvic nodes, in spite of its low differentiation grade and high potential aggressiveness, and even though the patient was already symptomatic. Two years after surgery the patient is disease free, which is consistent with the evaluation of the surgical specimen, but unusual in poorly differentiated neoplasms.

BRCA2 germline mutations in primary cancer of the fallopian tube.

Germline mutations of BRCA1 and BRCA2 genes confer susceptibility to breast and ovarian cancer. It has been recently reported that BRCA1/2 mutations may also predispose to fallopian tube cancer. We report the presence of germline BRCA2 gene mutations in three out of four subjects with fallopian tube cancer diagnosed in a two-year time span at our clinic. The mothers of two of these women suffered from breast or ovarian carcinoma. These results suggest on one hand that in patients with a history suggestive for a heredofamilial breast/ovarian cancer syndrome fallopian tube carcinoma is associated with high risk of BRCA2 mutation, and on the other hand that in patients/individuals with germline BRCA2 gene mutations in whom a prophylactic oophorectomy is performed, removal of fallopian tubes may be considered.

Obesity reduces the expression of GLUT4 in the endometrium of normoinsulinemic women affected by the polycystic ovary syndrome.

GLUT4 is the most important glucose transporter in insulin-dependent tissues. A decrease of its expression by the adipocytes was reported in polycystic ovary syndrome (PCOS), regardless of obesity and glucose tolerance. In PCOS, abnormal menstrual cycles, abnormal insulin secretory patterns, and obesity, which are risk factors for endometrial diseases, frequently coexist. The endometrial effects of insulin are direct through specific insulin receptors. However, it is unknown whether the endometrium expresses GLUT4 and can be considered an insulin-regulated tissue. In this study, we investigated this question, and we investigated whether obesity modulates this expression in PCOS normoinsulinemic patients. We assayed GLUT4 in the endometrial samples from 18 normoinsulinemic PCOS patients and 9 controls in the advanced follicular phase of the cycle; 10 patients were lean and 8 obese, and all were aged between 23 and 32 years. Most tissue was immediately frozen for RT-PCR; some tissue was saved for histology and immunohistochemistry. GLUT4 mRNA expression was measured in three samples for every patient and expressed as mean +/- SE of an arbitrary unit. In obese PCOS subjects, endometrial GLUT4 expression was significantly lower than in the lean ones (24.0 +/- 6.8 vs. 65.2 +/- 24.4; P < 0.005) and the controls (53.2 +/- 10.7). Lean PCOS and control subjects showed similar values. GLUT4 immunostaining was strong in the epithelial and absent in the stromal cells. We demonstrated endometrial GLUT4 expression. The similar results in lean PCOS and control subjects suggest that endometrial GLUT4 expression is not affected by PCOS itself, whereas it is reduced by obesity in PCOS patients.

A novel Q3034R BRCA2 germline mutation identified in a fallopian tube cancer patient.

Fallopian tube cancer (FTC) accounts for 0.1-0.5% of all gynaecological malignancies, so that very few studies have demonstrated a significant linkage between this cancer type and BRCA1/BRCA2 mutations. We report the identification of a novel germline mutation (Q3034R) in BRCA2 gene in a 41-year-old patient. The nucleotide change (CAG > CGG) abolishes a DdeI restriction site, making genotype identification rapid and inexpensive. Our findings support the hypothesis that the primary FTC should be considered, at least in a subset of patients, as a BRCA2-associated tumor. Genetic counselling could result, in these cases, in early diagnosis of genetically predisposed individuals.