Natkrita Pohthipornthawat

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.

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..

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.