Tarinee Manchana

Clinicopathological characteristics and survival outcomes of women aged ≤45 and >45 years with endometrial adenocarcinoma in tertiary referral hospital: a 21-year cohort study

Objective This study aimed to compare clinicopathological characteristics and oncological outcomes in patients with endometrial cancer aged ≤45 and >45 years, with a focus on identifying distinct traits and prognostic factors in younger patients. Design A retrospective cohort study. Setting The study was conducted at King Chulalongkorn Memorial Hospital, Bangkok, Thailand, with a restricted study population from 1996 to 2016. Participants A total of 1114 patients diagnosed with endometrial cancer and underwent surgery were strictly selected, excluding those who had received primary radiotherapy or had uterine sarcoma. Among the population, 188 patients (16.9%) were ≤45 years old and 926 patients (83.1%) were >45 years old. Outcome measures The primary outcome measures were disease-free survival (DFS) and overall survival (OS) at 5, 10 and 15 years, with an analysis of survival rates based on patient age groups and prognostic factors. Results Younger patients (≤45 years) displayed significantly higher rates of obesity, nulliparity and polycystic ovary syndrome (PCOS), as well as favourable pathological characteristics such as well-differentiated tumours and lower rates of myometrial invasion. They also exhibited better long-term survival outcomes, the DFS rates at 5, 10 and 15 years were 89.6% (95% CI: 84.0 to 98.3), 85.9% (95% CI: 79.0 to 90.6) and 76.8% (95% CI: 63.3 to 85.9), respectively, compared with 77.6% (95% CI: 74.6 to 80.2), 69.2% (95% CI: 65.6 to 72.5) and 53.5% (95% CI: 48.0 to 58.6) in the older group. Similarly, the OS rates at 5, 10 and 15 years were 94.7% (95% CI: 90.1 to 97.2), 91.7% (95% CI: 85.4 to 95.3) and 74.0% (95% CI: 51.7 to 87.2), respectively, compared with 86.9% (95% CI: 84.4 to 89.0), 76.6% (95% CI: 73.0 to 79.7) and 60.7% (95% CI: 55.0 to 65.8) in the older group. Independent prognostic factors consist of non-endometrioid histology, involvement of the lower uterine segment and cervix, omental metastasis, lymphovascular invasion and advanced stage. Conclusions Young patients with endometrial cancer exhibit distinct favourable clinicopathological characteristics associated with better oncological outcomes compared with older patients. However, certain aggressive disease features should be taken into consideration as they have a negative influence on prognosis significantly. These insights emphasise the need for targeted management strategies and further research.

Simplifying Mismatch Repair Deficiency Screening in Endometrial Adenocarcinoma: Immunohistochemistry with Two-Antibody Panel (PMS2 and MSH6)

Mismatch repair deficiency (dMMR) is a well-established characteristic of endometrial adenocarcinoma and is crucial in screening for Lynch syndrome, guiding adjuvant treatment decisions, and identifying candidates for immune checkpoint inhibitors. The traditional approach to dMMR screening involves a four-antibody panel, but a simplified two-antibody method utilizing PMS2 and MSH6 has shown promise. This study aims to compare the diagnostic performance of the simplified two-antibody method with the traditional four-antibody panel in endometrial cancer samples. We conducted a retrospective cohort study on endometrial carcinoma cases diagnosed between 2013 and 2022. We compared the diagnostic performance of the two-antibody panel with the traditional four-antibody panel in detecting dMMR. Clinical data and immunohistochemistry results were collected, and agreement between the two methods was evaluated using Cohen's kappa coefficient. 304 endometrial cancer cases were included, with 27% demonstrating loss of at least one MMR protein using the four-antibody panel. The two-antibody method detected MMR deficiency in 26.6% of cases, with a high agreement rate of 98.8% between the two methods. Only one case showed discordant results, prompting further investigation. The simplified two-antibody MMR IHC screening approach using PMS2 and MSH6 showed high concordance with the traditional four-antibody panel. This suggests its potential as an alternative method for reflex MMR status testing in endometrial adenocarcinoma. The implementation of this approach could streamline the diagnostic process, reduce costs, and improve the detection of Lynch syndrome in affected individuals and their families. Further studies with larger cohorts and long-term follow-up are needed to validate these findings and assess the clinical implications of this approach in routine practice.

Lynch Syndrome in Thai Endometrial Cancer Patients

Lynch syndrome increases lifetime risk of endometrial cancer to 40-60%. Screening with molecular tumor testing for mismatch repair (MMR) proteins have been recommended. This study aims to evaluate the incidence of MMR deficiency and germline mutation in endometrial cancer Thai patients. Immunohistochemistry for MMR proteins, including MLH1, MSH2, MSH6 and PMS2 were tested in 166 surgical specimens. Patients who had MMR deficiencies were offered genetic counseling and a germline testing using gene-panel next generation sequencing. Fifty-eight of 166 patients (34.9%) had one or more MMR deficiencies which were: MLH1 and PMS2 in 42 patients (25.3%), MSH2 and MSH6 in 11 patients (6.6%), and MSH6 in 5 patients (3.0%). Of the 40 patients (24.1%) who met the revised Bethesda guidelines, 19 patients (47.5%) had MMR deficiency. In contrast, MMR deficiency was found in 39 of the 126 patients (31.0%) who did not meet the revised Bethesda guidelines. A total of 27 patients with MMR deficiencies agreed to have germline genetic testing. Germline MMR mutations were detected in 5 patients (18.5%) including MSH6 (n=2), PMS2 (n=2), and MLH1 mutations (n=1). Incidental germline mutations in other genes were detected in 3 patients (1 BRCA1, 1 PTEN, and 1 BARD1). Among 5 Lynch syndrome patients, 2 patients (40%) did not meet the revised Bethesda guidelines. Eight patients who met the revised Bethesda Guidelines but having MMR proficiency had genetic testing, but no germline mutation was detected. MMR deficiencies were detected in 34.9% of the endometrial cancer patients. Germline mutations were diagnosed in 3.0% of this cohort (5/166 patients). Lynch syndrome screening with MMR immunohistochemistry should be considered in all patients regardless of personal or family history of Lynch syndrome-related cancers.

Prevalence of Tissue BRCA Gene Mutation in Ovarian, Fallopian Tube, and Primary Peritoneal Cancers: A Multi-Institutional Study

Ovarian, fallopian tube, or primary peritoneal cancer patients with BRCA gene mutation have enhanced sensitivity to platinum-based regimens and PARP inhibitors. However, the knowledge regarding BRCA mutation in Thai patients is limited. This study aimed at identifying the prevalence and characteristics of somatic and germline BRCA 1 and 2 mutations in Thai patients with these cancers. The paraffin blocks of tumors with histology of high grade serous, high grade endometrioid, or clear cell carcinoma obtained between June 2016 and December 2017 were analyzedto evaluate BRCA mutation using next-generation sequencing system. Blood or normal tissue paraffin blocks of positive patients were further tested for germline BRCA mutation. Tissue paraffin blocks of 178 patients were collected but only 139 were analyzed. Positive BRCA mutation was identified in 24 patients (17.3%): BRCA1 in 13 cases, BRCA2 in 10 cases, and BRCA1 and 2 in the rest one. Germline mutation study in blood or normal tissue in 23 positive patients revealed BRCA mutation in 14 cases, BRCA1 in 8 cases and BRCA 2  in 6 cases. Overall, the prevalence of somatic and germline mutation was 6.5% (9 out of 138 patients) and 8.7% (14 out of 138 patients), respectively. The most common histology associated with BRCA mutation was high grade serous cancer (27.3%). No significant difference was found between patients with or without BRCA mutation in terms of stage, outcome, platinum status, and survival outcome. BRCA mutation was demonstrated in less than 10% of Thai ovarian cancer patients. Higher rate of mutation was found in high grade serous cancer..