An analysis of clinical, surgical, pathological and molecular characteristics of endometrial cancer according to mismatch repair status. A multidisciplinary approach

Since 2016, our hospital has applied tumor testing with immunohistochemistry (IHC) in endometrial cancer in order to detect mutations of mismatch repair genes (MMR). All cases with MMR deficiency proteins expression are sent for genetic testing, except those with MLH1 protein deficiency, in which case genetic testing is performed if negative for promoter hypermethylation. The primary aim of this study was to investigate the ability of our algorithm to identify Lynch syndrome (LS). The Secondary aims were to investigate the relationship between MMR status and clinicopathological features and prognosis of primary endometrial cancer (EC). From January 2016 to December 2018, 239 patients with EC were retrospectively analyzed and subdivided according to MMR status. Patients were divided in three groups: MMR proficient, LS and Lynch-like cancer (LLC). LS was characterized by a lower age and BMI, more use of contraceptive and less use of hormonal replacement therapy, nulliparity and a trend versus a better prognosis. LLC appeared more related to MMR proficient than LS and exhibited a more aggressive behavior. Our multidisciplinary approach permitted a correct diagnosis of germline mutation in patients with newly diagnosis EC and it confirmed clinicopathologic and prognostic characteristics of LS

Progetto e realizzazione di un laboratorio per attività di Penetration Testing, Red Teaming e Blue teaming in ambiente Active Directory

Il progetto di tirocinio e tesi è stato pianificato con l’obiettivo di creare un laboratorio di macchine virtuali in cui configurare un dominio Active Directory, che sarebbe servito poi all’azienda per attività di penetration testing su di un ambiente controllato. Un laboratorio sul quale testare le vulnerabilità è fondamentale, poiché effettuare attività di penetration testing e vulnerability assessment sull’ambiente di produzione potrebbe comprometterne il corretto funzionamento. Utilizzando un laboratorio non in produzione è possibile anche studiare e approfondire le tematiche legate ad Active Directory al fine di creare nuovi scenari o percorso d’attacco. Grazie alla tecnica di Infrastructure as Code (IaC), è stato possibile definire la struttura del laboratorio sotto forma di codice in appositi file di configurazione. Una volta che il laboratorio è stato creato con successo, lo stesso è stato configurato per assumere le fattezze di un ambiente Active Directory di una compagnia reale. È stato quindi eseguito un penetration test con lo scopo di individuare le vulnerabilità e sfruttarle per esfiltrare informazioni sensibili del sistema. Contemporaneamente, sono stati annotati i log che vengono prodotti durante l’esecuzione di questi attacchi da parte di un intruso. Questi log sono poi stati analizzati per scoprire se è possibile rilevare un attacco solamente controllando gli eventi che questo scatena sul sistema

Conservative treatment of early endometrial cancer

Endometrial cancer is the most common cancer of the female genital tract in Europe and in the United States. Endometrial cancer has increased 21% in incidence since 2008, and the death rate has increased more than 100% over the past two decades. Approximately 15% of patients with endometrial cancer are premenopausal. The aim of this review is to discuss the conservative management of endometrial cancer. A number of studies largely support the conservative treatment of endometrial carcinoma in women desiring future fertility. We focus on the role of progestin hormonal therapy, including the risks associated with non-standard care, appropriate candidate selection, expected outcomes, various progestin agents and recommended follow-up. J. Cell. Physiol. © 2012 Wiley Periodicals, Inc

New insights in endometrial carcinogenesis

Endometrial carcinoma is the most common cancer of the female genital tract in Europe and in the United States. Despite advances in defining the biology of endometrial carcinomas, there has been poor progress in determining markers that distinguish preinvasive endometrial proliferations. The aim of this review is to highlight the most recent studies regarding the molecular markers involved in endometrial adenocarcinoma pathogenesis and carcinogenesis. We focus on studies that describe markers with potential to progress from endometrial hyperplasia to invasive disease

Cervical cancer in pregnancy: Analysis of the literature and innovative approaches

Cervical cancer is one of the most common gynecological malignancies diagnosed during pregnancy although, fortunately, it is a rare event. In majority of cases, the management of cervical cancer in pregnant women is not different from nonpregnant women and prognosis seems not compromised by pregnancy. The association between cancer and pregnancy appears to be a significant challenge for women and specialists and the decisions about therapy must be individualized and taken by a multidisciplinary team. This review is focused on cervical cancer in pregnancy. The aim is to discuss the diagnosis, potential biomarkers and molecular aspects, therapeutic approaches, and prognosis from intraepithelial cervical neoplasia to invasive cervical cancer (early and advanced stages) in different gestational ages. We provide an overview of the current literature regarding the treatment strategies of concurrent pregnancy and cervical cancer cases and we propose some clinical advices to help clinicians to manage this condition. A mention about the effects of the conservative therapy (as conization) on fertility, the human papillomavirus vaccine in pregnant women and our center's experience with obstetrical and oncological outcomes are reported

Does microcolposcopy protect patients with CIN and unsatisfactory colposcopy from the risk of incomplete excision of disease at the time of conization?

To evaluate the effectiveness of microcolposcopy in preventing incomplete electrosurgical excision at the endocervical cone margin in patients with CIN and unsatisfactory colposcopy

pRb2/p130 and VEGF expression in endometrial carcinoma in relation to angiogenesis and histopathologic tumor grade

PURPOSE: Endometrial cancer is the most common gynecologic malignancy. Established prognostic factors are histologic grade, depth of myometrial invasion, and extrauterine spread including retroperitoneal lymph node metastases. Tumorigenesis is a multistep process involving different genetic changes resulting in uncontrolled cellular proliferation, inhibition of apoptosis, and enhanced vascular proliferation among other events. Angiogenesis, the formation of new blood vessels from a preexisting vascular network, is necessary for invasive tumor growth and metastasis and constitutes an important point in the control of cancer progression. The pathogenesis of the angiogenetic phenotype may involve the inactivation of different tumor suppressor genes. EXPERIMENTAL DESIGN: We investigated the relationship between the expression levels of VEGF and the retinoblastoma family member pRb2/p130 in endometrial carcinoma in relation to histopathologic tumor grade in a cohort of 50 patients. RESULTS: We found that VEGF and pRB2/p130 expression were inversely correlated. Additionally, high grade tumors presented a significantly lower number of cells expressing pRb2/p130 when compared to low grade tumors. A significant positive correlation was found, by means of the Spearman coefficient, between VEGF expression and binary grading (0.450, p-value < 0.005) which is an architectural grading system that uses low-magnification assessment of amount of solid growth, pattern of invasion, and presence of necrosis to divide endometrioid carcinomas into low- and high-grade tumors. Additionally, we also found a negative correlation between pRb2/p130 expression levels and binary grading (-0.595, p-value < 0.005). Interestingly, we also found that VEGF and pRb2/p130 expression levels were not related to staging (p-value > 0.005). CONCLUSIONS: These results open up a new perspective including novel markers that, combined together, may be useful in patient screening for endometrial cancer aggressiveness