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Endometrial Cancer (EC) is one of the most common malignancies in women in developed countries. Molecular characterization of different biotypes may improve clinical management of EC. The Cancer Genome Atlas (TCGA) project has revealed four prognostic EC subgroups: POLE, MSI; Copy Number Low (CNL) and Copy Number High (CNH). The goal of this study was to develop a method to classify tumors in any of the four EC prognostic groups using affordable molecular techniques. Ninety-six Formalin-Fixed Paraffin-embedded (FFPE) samples were sequenced following a NGS TruSeq Custom Amplicon low input (Illumina) protocol interrogating a multi-gene panel. MSI analysis was performed by fragment analysis using eight specific microsatellite markers. A Random Forest classification algorithm (RFA), considering NGS results, was developed to stratify EC patients into different prognostic groups. Our approach correctly classifies the EC patients into the four TCGA prognostic biotypes. The RFA assigned the samples to the CNH and CNL groups with an accuracy of 0.9753 (p

The objective of this study was to evaluate the efficacy of one-step nucleic acid amplification (OSNA) for the detection of sentinel lymph node (SLN) metastasis compared to standard pathological ultrastaging in patients with early-stage endometrial cancer (EC). A total of 526 SLNs from 191 patients with EC were included in the study. 379 SLNs (147 patients) were evaluated by both methods, OSNA and standard pathological ultrastaging. The central 1-mm portion of each lymph node was subjected to semi-serial sectioning at 200-μm intervals and examined by hematoxylin-eosin and immunohistochemistry with CK19; the remaining tissue was analysed by OSNA for CK19 mRNA. The OSNA assay detected metastases in 19.7% of patients (14.9% micrometastasis and 4.8% macrometastasis), whereas pathological ultrastaging detected metastasis in 8.8% of patients (3.4% micrometastasis and 5.4% macrometastasis). Using the established cut-off value for detecting SLN metastasis by OSNA in EC (250 copies/μl), the sensitivity of the OSNA assay was 92%; specificity was 82%; diagnostic accuracy was 83%, and the negative predictive value was 99%. Discordant results between both methods were recorded in 20 patients (13.6%). OSNA resulted in an upstaging in 12 patients (8.2%). OSNA could aid in the identification of patients requiring adjuvant treatment at the time of diagnosis.

The objective of this study was to evaluate the efficacy of one-step nucleic acid amplification (OSNA) for the detection of sentinel lymph node (SLN) metastasis compared to standard pathological ultrastaging in patients with early-stage endometrial cancer (EC). A total of 526 SLNs from 191 patients with EC were included in the study, and 379 SLNs (147 patients) were evaluated by both methods, OSNA and standard pathological ultrastaging. The central 1 mm portion of each lymph node was subjected to semi-serial sectioning at 200 μm intervals and examined by hematoxylin–eosin and immunohistochemistry with CK19; the remaining tissue was analyzed by OSNA for CK19 mRNA. The OSNA assay detected metastases in 19.7% of patients (14.9% micrometastasis and 4.8% macrometastasis), whereas pathological ultrastaging detected metastasis in 8.8% of patients (3.4% micrometastasis and 5.4% macrometastasis). Using the established cut-off value for detecting SLN metastasis by OSNA in EC (250 copies/μL), the sensitivity of the OSNA assay was 92%, specificity was 82%, diagnostic accuracy was 83%, and the negative predictive value was 99%. Discordant results between both methods were recorded in 20 patients (13.6%). OSNA resulted in an upstaging in 12 patients (8.2%). OSNA could aid in the identification of patients requiring adjuvant treatment at the time of diagnosis., El objetivo de este estudio fue evaluar la eficacia de la amplificación de ácido nucleico en un solo paso (OSNA) para la detección de metástasis en el ganglio linfático centinela (GC) en comparación con la ultraestadificación patológica estándar en pacientes con cáncer de endometrio (CE) en estadio temprano. Se incluyeron en el estudio un total de 526 SLN de 191 pacientes con EC, y 379 SLN (147 pacientes) fueron evaluados por ambos métodos, OSNA y ultraestadificación patológica estándar. La porción central de 1 mm de cada ganglio linfático se sometió a un seccionamiento semiserie a intervalos de 200 μm y se examinó mediante hematoxilina-eosina e inmunohistoquímica con CK19; el tejido restante fue analizado por OSNA para ARNm de CK19. El ensayo OSNA detectó metástasis en el 19,7 % de los pacientes (14,9 % micrometástasis y 4,8 % macrometástasis), mientras que la ultraestadificación patológica detectó metástasis en el 8,8 % de los pacientes (3. 4% micrometástasis y 5,4% macrometástasis). Usando el valor de corte establecido para detectar metástasis SLN por OSNA en EC (250 copias/μL), la sensibilidad del ensayo OSNA fue del 92 %, la especificidad fue del 82 %, la precisión diagnóstica fue del 83 % y el valor predictivo negativo fue del 99 % Se registraron resultados discordantes entre ambos métodos en 20 pacientes (13,6%). OSNA resultó en una sobreestadificación en 12 pacientes (8,2%). OSNA podría ayudar en la identificación de pacientes que requieren tratamiento adyuvante en el momento del diagnóstico. Se registraron resultados discordantes entre ambos métodos en 20 pacientes (13,6%). OSNA resultó en una sobreestadificación en 12 pacientes (8,2%). OSNA podría ayudar en la identificación de pacientes que requieren tratamiento adyuvante en el momento del diagnóstico. Se registraron resultados discordantes entre ambos métodos en 20 pacientes (13,6%). OSNA resultó en una sobreestadificación en 12 pacientes (8,2%). OSNA podría ayudar en la identificación de pacientes que requieren tratamiento adyuvante en el momento del diagnóstico.

The quality of pathological assessment is crucial for the safety of patients with cervical cancer if pelvic lymph node dissection is to be replaced by sentinel lymph node (SLN) biopsy. Central pathology review of SLN pathological ultrastaging was conducted in the prospective SENTIX/European Network of Gynaecological Oncological Trial (ENGOT)-CX2 study. All specimens from at least two patients per site were submitted for the central review. For cases with major or critical deviations, the sites were requested to submit all samples from all additional patients for second-round assessment. From the group of 300 patients, samples from 83 cases from 37 sites were reviewed in the first round. Minor, major, critical, and no deviations were identified in 28%, 19%, 14%, and 39% of cases, respectively. Samples from 26 patients were submitted for the second-round review, with only two major deviations found. In conclusion, a high rate of major or critical deviations was identified in the first round of the central pathology review (28% of samples). This reflects a substantial heterogeneity in current practice, despite trial protocol requirements. The importance of the central review conducted prospectively at the early phase of the trial is demonstrated by a substantial improvement of SLN ultrastaging quality in the second-round review. ispartof: CANCERS vol:12 issue:5 ispartof: location:Switzerland status: published

Este artículo se encuentra disponible en la página web de la revista en la siguiente URL: https://ecancer.org/en/journal/article/929-relevance-of-minor-discrepancies-at-second-pathology-review-in-gynaecological-cancer Aim: To determine the incidence of discrepancy rate between the initial pathology diagnosis and referral diagnosis in women with gynaecological cancer. Methods: A retrospective observational study was performed including all consecutive patients with gynaecological cancer referred and who underwent pathologic review between January 2013 and May 2017. Discrepancies were minor when future treatment was not altered or major when the treatment was modified. Results: A total of 259 patients were included. The original diagnosis was ovarian cancer (n = 126, 48.6%), endometrial cancer (n = 84, 32.4%), cervical cancer (n = 43, 16.6%) and vulvar cancer (n = 6, 2.3%). Eighteen women (6.9%) had major discrepancies and 69 patients (26.6%) had minor discrepancies. The main reason for the minor discrepancy was tumour grade or histology subtype. Regarding ovarian cancer, 13 out of 16 patients had minor discrepancies at histology subtype among serous, endometrioid, mucinous or undifferentiated tumours. The main issue for the minor discrepancy in patients with cervical cancer was among different subtype of cervical adenocarcinoma. Minor discrepancies due to tumour grade were also observed in 14, 19, 8 and 3 patients with endometrial, ovarian, cervical and vulvar cancer, respectively. Conclusions: A second pathology review also adds valid information in those cases with minor discrepancies leading to a difference in patients´ counselling regarding follow-up and prognosis.

Objective To describe the surgical technique of a subxiphoid approach to remove cardiophrenic lymph nodes in women with advanced ovarian cancer. Materials and methods The first step is to dissect and separate the anterior insertions of the diaphragm at the xiphoid appendix. Thus, the parietal peritoneum and the upper fibres of the transversus abdominis muscle are incised. Then, the anteroinferior mediastinum is identified and dissected. Diaphragmatic deinsertion may be extended 5-7 cm laterally to the xiphoid appendix following the inferior costal margin according with the localization of the enlarged lymph nodes. Thus, the dissection of the anterolateral cardiophrenic space allows the identification of both pleura. In addition, the vertical dissection of the anterior cardiophrenic space allows the removal of enlarged lymph nodes. However, it is important to bear in mind at this time that the unintentional opening of the pleura is possible. To reduce this risk, a careful dissection of the anterior cardiophrenic fat tissue is essential. Moreover, a careful dissection will avoid damage at the left phrenic nerve as well as the left pericardiophrenic artery and vein. After removing the cardiophrenic fat tissue, the diaphragm is sutured at the lower costal margin by using separated stiches of absorbable 2-0 suture. Conclusion The subxiphoid approach to resect cardiophrenic lymph nodes is a feasible surgical technique. In addition, it reduces the possibility of opening the pleural cavity, while avoiding a diaphragmatic incision, in comparison with the standard trans-diaphragmatic surgical approach.

ObjectiveThe aim of this study was to describe the clinical and oncological outcomes of women with malignant bowel obstruction (MBO) for relapsed ovarian cancer and peritoneal carcinomatosis.MethodsA retrospective cohort study was performed in all consecutive patients admitted at Instituto Valenciano de Oncología, Valencia, Spain, between July 2013 and July 2016 with MBO for relapsed ovarian cancer and peritoneal carcinomatosis. All patients underwent the same protocol of conservative management. Surgical treatment was indicated only in selected cases.ResultsThere were a total of 22 patients presenting 59 episodes of MBO; 17 (77.2%) of those patients presented more than 1 episode of MBO. All patients had serous epithelial ovarian cancer; 18 (81.8%) were high grade, and 4 (18.2%) low-grade tumors. The median (range) number of episodes per patient was 3 (range, 1–7) with a mean length of hospitalization of 13 (SD, 13.6) days. The median time interval between episodes of MBO (54 episodes in 17 patients) was 17 days (range, 1–727 days). Twenty of 22 patients died with a median overall survival time from the first episode of MBO of 95 days (95% confidence interval, 49–124 days).ConclusionsPatients with MBO due to relapsed epithelial ovarian cancer in the peritoneal carcinomatosis setting have a short life expectancy, presenting a median of 3 episodes of MBO until death, with a short time interval between episodes. These findings show that bowel obstruction can represent a constant status over time until death.

The aim of this study was to determine oncological outcomes and incidence of lymph node (LN) metastases in women who underwent systematic pelvic and paraaortic lymphadenectomy for surgical staging of apparent stage I low-grade epithelial ovarian cancer (LGEOC). A retrospective study was performed at nine institutions across Europe and the US, and patients who underwent surgical staging for presumed stage I LGEOC between 2000 and 2016 were included. To ensure surgical quality, a minimum number of ≥10 pelvic and ≥10 paraaortic LNs was required. Patients with preoperative radiologic or clinical evidence of extraovarian or LN disease, and those with nonepithelial histology, were excluded. The overall incidence of LN metastases was 4.3% in the 163 evaluated patients, and the incidence of LN involvement in serous, endometrioid, and mucinous subtypes was 10.7, 1.5, and 0%, respectively. However, Upstaging due to LN involvement alone occurred in only 2.4% of the patients. Eighty-nine (54.6%) patients received adjuvant chemotherapy due to International Federation of Gynecology and Obstetrics stage IC or higher disease. The 5-year progression-free survival (PFS) and overall survival (OS) were 93.2% (95% confidence interval [CI] 89.4–97.1%) and 94.5% (95% CI 90.9–98.0%), respectively. There was no significant difference in PFS or OS between LN-negative and LN-positive patients. However, fewer patients received adjuvant chemotherapy in the LN-negative group. Multivariate analysis did not identify any independent prognostic factor of survival. The risk of LN involvement in nonserous apparent stage I LGEOC appears low, with a rate of

e14744 Background: Copy number alterations (CNA) constitutes a genomic hallmark that defines specific outcomes in gynecological neoplasms, as evidenced by the integrated analysis of the high-grade serous ovarian carcinoma (HGSOC) and endometrial carcinomas (EC) performed by the TCGA Consortium. The purpose of this study is to set up an NGS-based technology to obtain CNA profiles on formalin-fixed paraffin-embedded (FFPE) samples with clinical utility. Methods: FFPE blocks from 14 EC and 12 HGSOC were analyzed using a SureSelectXT custom panel plus OneSeq backbone, interrogating 147.000 SNPs (Agilent). CNA groups were defined in EC with a RF algorithm based on genotyping data as previously reported (Romero, ASCO 2018) and in HGSOC Homologous recombination deficiency (HRD) was determined by sequencing a serie of 35 HR genes. saasCNV pipeline was used to perform CNA calling. Results: Ten (38.50 %) of our cases were classified as CN Low (CNL), 8 as CN high (CNH)-RF (30.75 %) and 8 CNH-HRD (30.75 %). CNL profiles from EC and OC are homogenous in terms of genomic stability. CNH-RF and CNH-HRD cases harbor the highest percentage of genomic instability (p = 0.012) with distinct patterns of CNA. CNH-HRD is characterized by a higher ratio of genomic losses (p = 0.023). However, CNH-RF is mainly defined by gains (p = 0.011) (Table). Conclusions: Our NGS-based approach represents a FFPE clinically available procedure to define CNA alterations in gynecological cancer with distinct CNH patterns with prognostic potential.[Table: see text]

Gynecologic oncologists have an essential role to treat women with gynecological cancer. It has been demonstrated that specialized physicians who work in multidisciplinary teams to treat women with gynecological cancers are able to obtain the best clinical and oncological outcomes. However, the access to gynecologic oncologists for women with suspected gynecological cancer is scarce. Therefore, this review analyzes the importance of a specialized care of women with ovarian, cervical, endometrial and ovarian cancer. In addition, the roles of gynecologic oncologists who offer fertility-sparing treatment as well as their role to assist general gynecologists and obstetricians are also reviewed.

Although it is assumed that the combination of chemotherapy and radical surgery should be indicated in all newly diagnosed advanced-stage ovarian cancer patients, one of the main raised questions is how to select the best strategy of initial treatment in this group of patients, neoadjuvant chemotherapy followed by interval debulking surgery or primary debulking surgery followed by adjuvant chemotherapy. The selection criteria to offer one strategy over the other as well as a stepwise patient selection for initial treatment are described. Selecting the best strategy of treatment in newly diagnosed advanced stage ovarian cancer patients is a multifactorial and multidisciplinary decision. Several factors should be taken into consideration: (1) the disease factor, related to the extension and localization of the disease as well as tumor biology; (2) the patient factor, associated with patient age, poor performance status, and co-morbidities; and (3) institutional infrastructure factor, related to the lack of prolonged operative time, an appropriate surgical armamentarium, as well as well-equipped intensive care units with well-trained personnel.

5591Background: The Cancer Genome Atlas (TCGA) study for endometrial carcinomas (EC) defined four prognostic molecular biotypes based on POLE status, Microsatellite instability (MSI) and Copy Numbe...

Resumen Objetivo Conocer la prevalencia de adenocarcinoma de endometrio en pacientes con diagnostico de hiperplasia endometrial atipica tras biopsia endometrial. Pacientes y metodos Veinte pacientes con diagnostico de hiperplasia endometrial atipica tras biopsia endometrial histeroscopica en consulta y/o tras reseccion endometrial histeroscopica en quirofano. Resultados Se realizo una histerectomia a 15 pacientes y se encontraron 8 casos de adenocarcinoma de endometrio. Dos pacientes fueron reintervenidas mediante laparoscopia para realizar una linfadenectomia.

Robotic surgery is a new technology that has been progressively implemented to treat endometrial and cervical cancer. However, the use of robotic surgery for ovarian cancer is limited to a few series of cases and comparative studies with laparoscopy or laparotomy. The technical issues concerning robotic surgery, as well as clinical evidence, are described in this review. Robotic surgery in early stage, advanced stage, and relapsed ovarian cancer is discussed separately. In conclusion, evidence regarding the use of robotic-assisted surgical treatment for women with ovarian cancer is still scarce, but its use is progressively growing. Robotic-assisted staging in selected patients with early stage disease has an important role in referral institutions when well-trained gynecologists perform surgeries. However, minimally invasive surgery in patients with advanced stage or relapsed ovarian cancer requires further investigation, even in selected cases.

Lymph nodes are the main pathway in the spread of gynaecological malignancies, being a well-known prognostic factor. Lymph node dissection is a complex surgical procedure and requires surgical expertise to perform the procedure, thereby minimising complications. In addition, lymphadenectomy has value in the diagnosis, prognosis, and treatment of patients with gynaecologic cancer. Therefore, a video focused on the para-aortic retroperitoneal anatomy and the surgical technique of the extraperitoneal para-aortic lymphadenectomy is presented.

5594 Background: Several studies suggest that systemic immune response (SIR) and local immune response (LIR) have independent roles in multiple types of cancer. In endometrial cancer (EC), the correlation between SIR and LIR and its prognostic value remains unclear. Methods: A total of 146 EC patients (stage I-IV) who had undergone surgery from 2009 to 2015, were identified from a prospective institutional database. Lymphocyte/monocyte ratio (LMR) to represent SIR was calculated from preoperative blood samples. The presence of intratumoral and peritumoral infiltrating lymphocytes (TILs) on hematoxylin and eosin-stained slides was considered as a surrogate of LIR. LMR and TILs were correlated to pathological findings and survival outcomes (overall survival: OS, disease free survival: DFS). Results: A LMR cutoff value of 4.4 for survival was determined based on receiver operating characteristic (ROC) curve analysis. LMR high was significantly associated with endometrioid histology (p=0.03), lower grade (G1-2; p=0.003), < 50% myometrial invasion (p=0.01) and I-II stage (p=0.02). TILs were correlated with MSI-high (p LMR-high/no-TILs (87%) > LMR-low/TILs+ (71%) > LMR-low/no-TILs (61%). Conclusions: In our series of resected EC patients, SIR (defined by LMR) constituted an independent prognostic factor for OS and LIR for DFS. We did not find any correlation between SIR and LIR, but the combination of both higher SIR and LIR showed better OS. [Table: see text]

e17102Background: Different criteria have been used to identify LS in EC but not prospectively compared. Methods: We prospectively registered EC cases. We performed a three-generation pedigree, Mic...

e16516 Background: Endometrial cancer associated to Lynch Syndrome (EC-LS) is rare and several criteria are currently used to identify them; our aim is to compare several diagnostic methods and exp...

1543 Background: Prospective comparison of different methods for recognition of LS associated EC is lacking. Microsatellite instability (MSI) has been observed to be inconsistent as a prognostic factor in EC. The aim of this study was to analyze the impact of MSI and Mismatch Repair (MMR)-deficiency on LS identification and prognosis in a prospective series of EC treated in one single institution. Methods: Consecutive and prospective EC patients were included. Clinical data, family history of cancer and criteria for LS were evaluated. MSI and MMR protein expression were performed. When loss of MMR proteins and/or high MSI (MSI-H) was observed, complete sequencing and large genomic rearrangement analysis of germline MLH1, MSH2, MSH6 or PMS2 was done once MLH1 methylation was excluded. Results: Seventy-seven women diagnosed with EC were enrolled from 2009 to 2012 with a median age of 62 (31-87), 84% histological type I, 16% type II and FIGO stages I 83%, II 2.8%, III-IVA 7% and IVB 7%. Among which, 6.6% fulfilled revised Bethesda criteria (rBC), 5.3% criteria defined by the Society Gynecologic Oncology (>20%-to-25% risk of LS) (SGO) and 5.3% Amsterdam II criteria (AII). Seventy-four underwent surgery with curative-intent. Tumor tissue was unavailable in 5 cases for molecular analysis. MSI-H was observed in16 cases (22%) and 18 (24%) had loss of expression of MLH1 (14), MSH2 (2), MSH6 (1) or PMS2 (1). Nine MLH1 hypermethylation, 10 K-RAS and no BRAF mutations were identified. Four (5.5%) pathogenic MMR germline mutations were recognized: 2 MSH2, one MSH6 and one PMS2. One patient (25%) with MSH6 mutation did not fulfil rBC, SGO nor AII criteria and was identified both by MSI-H and loss of MSH6 expression. Median follow-up was 23.4 (0.2-76.3) months. No correlation between MSI-H, MMR gene mutation and relapse was observed in stage I-IVA EC. Conclusions: Based on these results, rBC, AII and SGO criteria for identification of LS in EC do not identify 25% of germline MMR gene mutations. No correlation with relapse and MSI-H could be identified.