Recent Advances in Classification and Histopathological Diagnosis of Ovarian Epithelial Malignant Tumours

Ovarian tumours are a heterogeneous group of neoplasms classified based on histopathologic type and grade of differentiation. They comprise a broad range of tumours from benign and borderline to malignant histotypes characterised by different histopathological, immunophenotypic and molecular features. The purpose of this chapter is to present an overview of the recent advances in the ovarian epithelial malignant tumours classification along with the histopathological, immunophenotypic and molecular diagnostic criteria highlighting areas of terminology discrepancies or changes and diagnostic challenges. These changes provide a better understanding of the ovarian tumours nature and lead to a more efficient therapeutic management of these pathological entities

Panic Attack during Elective Gastrointestinal Endoscopy

Background. Esophagogastroduodenoscopy (EGD) and colonoscopy (CS) can evoke anxiety, embarrassment, and discomfort. These concerns can culminate in panic attacks, which may traumatize patients and significantly decrease their compliance to the procedure. The objective of this study was to evaluate the relationship between preendoscopic anxiety and the possibility of a panic attack during an elective gastrointestinal endoscopy (EGE). Methods. The study population comprised of 79 Greek outpatients. The examination was carried out without the use of conscious sedation. Patients' anxiety levels were assessed before the procedure using the Greek version of the Spielberger State-Trait Anxiety Inventory (STAI-Y). Results. Seventy-nine patients were enrolled: 45 EGD and 34 CS. Females had higher state and trait anxiety levels than males (48.14 ± 7.94 versus 44.17 ± 7.43, P < 0.05; and 43.68 ± 6.95 versus 39.86 ± 7.46, P < 0.05). Patients who experienced panic attack had significantly higher levels of both trait and state anxiety, compared to those who were panic-free. There was no significant relationship between panic attacks and sex or type of procedure. Conclusions. Patients who experience panic attacks during endoscopic procedures appear to have significantly higher anxiety levels before the procedure. Administering the STAI questionnaire prior to the endoscopy seems to be a useful screening method for vulnerable patients

HER2 and TOP2A in high-risk early breast cancer patients treated with adjuvant epirubicin-based dose-dense sequential chemotherapy

<p>Abstract</p> <p>Background</p> <p>HER2 and TOP2A parameters (gene status, mRNA and protein expression) have individually been associated with the outcome of patients treated with anthracyclines. The aim of this study was to comprehensively evaluate the prognostic/predictive significance of the above parameters in early, high-risk breast cancer patients treated with epirubicin-based, dose-dense sequential adjuvant chemotherapy.</p> <p>Methods</p> <p>In a series of 352 breast carcinoma tissues from patients that had been post-operatively treated with epirubicin-CMF with or without paclitaxel, we assessed HER2 and TOP2A gene status (chromogenic in situ hybridization), mRNA expression (quantitative reverse transcription PCR), as well as HER2 and TopoIIa protein expression (immunohistochemistry).</p> <p>Results</p> <p>HER2 and TOP2A amplification did not share the same effects on their downstream molecules, with consistent patterns observed in HER2 mRNA and protein expression according to HER2 amplification (all parameters strongly inter-related, p values < 0.001), but inconsistent patterns in the case of TOP2A. TOP2A gene amplification (7% of all cases) was not related to TOP2A mRNA and TopoIIa protein expression, while TOP2A mRNA and TopoIIa protein were strongly related to each other (p < 0.001). Hence, TOP2A amplified tumors did not correspond to tumors with high TOP2A mRNA or TopoIIa protein expression, while the latter were characterized by high Ki67 scores (p = 0.003 and p < 0.001, respectively). Multivariate analysis adjusted for nodal involvement, hormone receptor status, Ki67 score and HER2/TOP2A parameters revealed HER2/TOP2A co-amplification (21.2% of HER2 amplified tumors) as an independent favorable prognostic factor for DFS (HR = 0.13, 95% CI: 0.02-0.96, p = 0.046); in contrast, increased HER2/TOP2A mRNA co-expression was identified as an independent adverse prognostic factor for both DFS (HR = 2.41, 95% CI: 1.31-4.42, p = 0.005) and OS (HR = 2.83, 95% CI: 1.42-5.63, p = 0.003), while high TOP2A mRNA expression was an independent adverse prognostic factor for OS (HR = 2.06, 95% CI: 1.23-3.46, p = 0.006). None of the parameters tested was associated with response to paclitaxel.</p> <p>Conclusions</p> <p>This study confirms the favorable prognostic value of HER2/TOP2A co-amplification and the adverse prognostic value of high TOP2A mRNA expression extending it to the adjuvant treatment setting in early high-risk breast cancer. The strong adverse prognostic impact of high HER2/TOP2A mRNA co-expression needs further validation in studies designed to evaluate markers predictive for anthracyclines.</p> <p>Trial registration</p> <p>Australian New Zealand Clinical Trials Registry <a href="http://www.anzctr.org.au/ACTRN12611000506998">ACTRN12611000506998</a>.</p

Deregulated expression of hnRNP A/B proteins in human non-small cell lung cancer: parallel assessment of protein and mRNA levels in paired tumour/non-tumour tissues

<p>Abstract</p> <p>Background</p> <p>Heterogeneous nuclear ribonucleoproteins (hnRNPs) of the A/B type (hnRNP A1, A2/B1, A3) are highly related multifunctional proteins participating in alternative splicing by antagonising other splicing factors, notably ASF/SF2. The altered expression pattern of hnRNP A2/B1 and/or splicing variant B1 alone in human lung cancer and their potential to serve as molecular markers for early diagnosis remain issues of intense investigation. The main objective of the present study was to use paired tumour/non-tumour biopsies from patients with non-small cell lung cancer (NSCLC) to investigate the expression profiles of hnRNP A1, A2/B1 and A3 in conjunction with ASF/SF2.</p> <p>Methods</p> <p>We combined western blotting of tissue homogenates with immunohistochemical examination of fixed tissue sections and quantification of mRNA expression levels in tumour versus adjacent normal-looking areas of the lung in the same patient.</p> <p>Results</p> <p>Our study, in addition to clear evidence of mostly uncoupled deregulation of hnRNPs A/B, has revealed hnRNP A1 to be the most deregulated protein with a high frequency of over-expression (76%), followed by A3 (52%) and A2/B1 (43%). Moreover, direct comparison of protein/mRNA levels showed a lack of correlation in the case of hnRNP A1 (as well as of ASF/SF2), but not of A2/B1, suggesting that different mechanisms underlie their deregulation.</p> <p>Conclusion</p> <p>Our results provide strong evidence for the up-regulation of hnRNP A/B in NSCLC, and they support the existence of distinct mechanisms responsible for their deregulated expression.</p

Soluble TNF Mediates the Transition from Pulmonary Inflammation to Fibrosis

BACKGROUND: Fibrosis, the replacement of functional tissue with excessive fibrous tissue, can occur in all the main tissues and organ systems, resulting in various pathological disorders. Idiopathic Pulmonary Fibrosis is a prototype fibrotic disease involving abnormal wound healing in response to multiple sites of ongoing alveolar epithelial injury. METHODOLOGY/PRINCIPAL FINDINGS: To decipher the role of TNF and TNF-mediated inflammation in the development of fibrosis, we have utilized the bleomycin-induced animal model of Pulmonary Fibrosis and a series of genetically modified mice lacking components of TNF signaling. Transmembrane TNF expression is shown to be sufficient to elicit an inflammatory response, but inadequate for the transition to the fibrotic phase of the disease. Soluble TNF expression is shown to be crucial for lymphocyte recruitment, a prerequisite for TGF-b1 expression and the development of fibrotic lesions. Moreover, through a series of bone marrow transfers, the necessary TNF expression is shown to originate from the non-hematopoietic compartment further localized in apoptosing epithelial cells. CONCLUSIONS: These results suggest a primary detrimental role of soluble TNF in the pathologic cascade, separating it from the beneficial role of transmembrane TNF, and indicate the importance of assessing the efficacy of soluble TNF antagonists in the treatment of Idiopathic Pulmonary Fibrosis

Uterine angiolipoleiomyoma. A case report and systematic literature review

Uterine angiolipoleiomyomas are rare, benign mixed mesenchymal lesions. A manifestation in the gynecological region is quite uncommon, with few cases described in the literature so far. We present an interesting case of a 59-year-old woman diagnosed with uterine angiolipoleiomyoma, and the results of the conducted systematic review of the literature. The patient presented with a pelvic mass masquerading as a leiomyoma on the ultrasound and postmenopausal vaginal bleeding. At laparotomy, a large uterus was noticed and the histopathology set the diagnosis of angiolipoleiomyoma. Immunohistochemistry revealed negativity for Melan-A and HMB-45 melanoma-specific antibodies and positivity for Van Gieson and orcein histochemical stains. We systematically reviewed the literature. The eligible articles were those written in English, excluding animal studies and studies reporting angiolipoleiomyomas in other regions beside the uterus. The present case is one of the 10 cases of uterine angiolipoleiomyoma reported in the literature. In 8 out of 11 (72.7%) cases, uterine angiolipoleiomyomas arose from the corpus of the uterus, while in 2 (18.1%) cases they were located at the cervix, and in one case (9%) angiolipoleiomyoma was located in the broad ligament. Concerning symptoms, four of the patients (36.4%) presented with abdominal and pelvic pain, two (18.1%) with postmenopausal vaginal bleeding, one with menometrorrhagia (9%), and one with uterine prolapse and cystocele (9%). Immunohistochemical staining of uterine angiolipoleiomyomas was positive for SMA in 4 patients (36.4%), positive for desmin in 3 cases (27.3%), positive for anti-S-100 protein antibody in 2 patients (18.1%), while in one case (9%) immunopositivity was observed for CD31. Only our case (9%) was also tested for CD34, Van Gieson and orcein, the first of these being negative and the other two positive (at the blood vessels in a specialized pattern). Three of the patients (27.3%) were also tested for HMB-45 and all three were immunonegative. In order to establish the diagnosis of uterine angiolipoleiomyomas, ultrasonography and additional MRI may help the preoperative prediction of a benign mass. Immunohistochemistry will show strong positivity of alpha-smooth muscle actin and desmin. Complete abdominal hysterectomy is the preferable treatment

Uterine angiolipoleiomyoma. A case report and systematic literature review

Uterine angiolipoleiomyomas are rare, benign mixed mesenchymal lesions. A manifestation in the gynecological region is quite uncommon, with few cases described in the literature so far. We present an interesting case of a 59-year-old woman diagnosed with uterine angiolipoleiomyoma, and the results of the conducted systematic review of the literature. The patient presented with a pelvic mass masquerading as a leiomyoma on the ultrasound and postmenopausal vaginal bleeding. At laparotomy, a large uterus was noticed and the histopathology set the diagnosis of angiolipoleiomyoma. Immunohistochemistry revealed negativity for Melan-A and HMB-45 melanoma-specific antibodies and positivity for Van Gieson and orcein histochemical stains. We systematically reviewed the literature. The eligible articles were those written in English, excluding animal studies and studies reporting angiolipoleiomyomas in other regions beside the uterus. The present case is one of the 10 cases of uterine angiolipoleiomyoma reported in the literature. In 8 out of 11 (72.7%) cases, uterine angiolipoleiomyomas arose from the corpus of the uterus, while in 2 (18.1%) cases they were located at the cervix, and in one case (9%) angiolipoleiomyoma was located in the broad ligament. Concerning symptoms, four of the patients (36.4%) presented with abdominal and pelvic pain, two (18.1%) with postmenopausal vaginal bleeding, one with menometrorrhagia (9%), and one with uterine prolapse and cystocele (9%). Immunohistochemical staining of uterine angiolipoleiomyomas was positive for SMA in 4 patients (36.4%), positive for desmin in 3 cases (27.3%), positive for anti-S-100 protein antibody in 2 patients (18.1%), while in one case (9%) immunopositivity was observed for CD31. Only our case (9%) was also tested for CD34, Van Gieson and orcein, the first of these being negative and the other two positive (at the blood vessels in a specialized pattern). Three of the patients (27.3%) were also tested for HMB-45 and all three were immunonegative. In order to establish the diagnosis of uterine angiolipoleiomyomas, ultrasonography and additional MRI may help the preoperative prediction of a benign mass. Immunohistochemistry will show strong positivity of alpha-smooth muscle actin and desmin. Complete abdominal hysterectomy is the preferable treatment