Chai Ariyasriwatana

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.

Role of Cyclooxygenase-2 (COX-2) Expression as a Prediction of Persistent Cervical Low Grade Squamous Intraepithelial Lesion (LSIL)

Cervical cancer rates have been decreasing due to improved screening programs targeting HPV infections. Cervical Intraepithelial Neoplasia (CIN), including CIN 1, can regress, persist, or progress, leading to patient anxiety. The expression of Cyclooxygenase-2 (COX-2) may serve as an indicator of poor cancer outcomes and could potentially predict the persistence of CIN 1. To assess the relationship between COX-2 expression and the persistence of low-grade squamous intraepithelial lesions (LSIL) or CIN 1. Additionally, to compare baseline characteristics between patients with persistent and regressive LSIL/CIN 1. This case-control study included patients diagnosed with CIN 1 at least 12 months prior to the study started and followed up between May 2019 and April 2020. Pelvic examination and liquid-based cytology collection were performed. Participants were divided into two groups: regressive and persistent, based on current examination results. Previous cervical biopsy slides were reviewed by two gynecologic pathologists to confirm the CIN 1 diagnosis. Paraffin blocks from selected samples underwent immunohistochemistry staining to evaluate COX-2 expression, which was assessed using the Allred score. Clinical risk factors, cervical cytology, HPV genotype, and Allred scores were analyzed. Of the 161 patients recruited, 132 were in the regressive group and 29 in the persistent group, yielding a regression rate of 81.99%. COX-2 expression was observed in 83.8% of the patients. In the regressive group, 110 out of 132 patients tested positive for COX-2, while 25 out of 29 patients in the persistent group were COX-2 positive. Median Allred scores were similar between the groups, with no significant correlation between COX-2 expression and persistent LSIL/CIN 1 (p = 0.663). Furthermore, there was no significant correlation between Allred scores, high-risk HPV infection, and high-risk HPV status (p = 0.66 and p = 0.80). Persistent detection of high-risk HPV was found to be a significant risk factor for persistent LSIL in univariate analysis (p = 0.001), but not in multivariate analysis. COX-2 expression and HPV status do not appear to predict persistent LSIL/CIN 1. Further research is needed to identify reliable predictors for the persistence of LSIL/CIN 1.