Highly Sensitive Microsatellite Instability and Immunohistochemistry Assessment in Endometrial Aspirates as a Tool for Cancer Risk Individualization in Lynch Syndrome.

Women with Lynch syndrome (LS) are at increased risk of endometrial cancer (EC), among other tumors, and are characterized by mismatch repair (MMR) deficiency and microsatellite instability (MSI). While risk-reducing gynecologic surgeries effectively decrease EC incidence, doubts arise regarding the appropriate timing of the surgery. We explored the usefulness of highly sensitive MSI (hs-MSI) assessment in endometrial aspirates for individualizing gynecologic surveillance in LS carriers. Ninety-three women with LS, 25 sporadic EC patients (9 MMR-proficient and 16 MMR-deficient), and 30 women with benign gynecologic disease were included in this study. hs-MSI was assessed in prospectively collected endometrial aspirates in 67 LS carriers, EC cases, and controls. MMR, PTEN, ARID1A, and PAX2 protein expression patterns were evaluated in the LS samples. Follow-up aspirates from 8 LS carriers were also analyzed. Elevated hs-MSI scores were detected in all aspirates from MMR-deficient EC cases (3 LS and 16 sporadic) and negative in aspirates from controls and MMR-proficient EC cases. Positive hs-MSI scores were also detected in all 4 LS aspirates reported as complex hyperplasia. High hs-MSI was also present in 10 of 49 aspirates (20%) from LS carriers presenting a morphologically normal endometrium, where MMR protein expression loss was detected in 69% of the samples. Interestingly, the hs-MSI score was positively correlated with MMR-deficient gland density and the presence of MMR-deficient clusters, colocalizing PTEN and ARID1A expression loss. High hs-MSI scores and clonality were evidenced in 2 samples collected up to 4 months before EC diagnosis; hs-MSI scores increased over time in 5 LS carriers, whereas they decreased in a patient with endometrial hyperplasia after progestin therapy. In LS carriers, elevated hs-MSI scores were detected in aspirates from premalignant and malignant lesions and normal endometrium, correlating with MMR protein loss. hs-MSI assessment and MMR immunohistochemistry may help individualize EC risk assessment in women with LS.

Risk Factors for Recurrence after Robot-Assisted Radical Hysterectomy for Early-Stage Cervical Cancer: A Multicenter Retrospective Study.

This retrospective analysis aimed to assess the risk factors for recurrence in patients diagnosed with early-stage cervical cancer (≤IB1 or IIA1, FIGO 2009) undergoing robot-assisted radical hysterectomy in Spain and Portugal between 2009 and 2018. A second primary objective was to audit the oncological outcomes according to quality indicators (QI) proposed by the European Society of Gynecology Oncology (ESGO). The study population included 239 women. After a median follow-up of 51 months, recurrence occurred in 26 patients (10.9%). Independent factors for recurrence were clinical tumor size > 20 mm (hazard ratio (HR) 2.37), adenocarcinoma as histological type (HR 2.51), positive pelvic lymph nodes (HR 4.83), tumor grade 2 (HR 4.99), tumor grade 3 (HR 8.06), and having not performed sentinel lymph node biopsy (SLNB) (HR 4.08). All 5 QI selected were surpassed by our results. In patients with early-stage cervical cancer undergoing robotic radical hysterectomy, clinicians should be aware that tumor grade 2 and 3, tumor size > 20 mm, adenocarcinoma, positive pelvic nodes, and lack of performance of SLNB are risk factors for recurrence. Fulfillment of QI targets of the ESGO might be considered as an objective oncological outcome indicator supporting the minimally invasive approach for early-stage cervical cancer treatment.