Chao-Cheng Huang

A comparative analysis of MMR immunohistochemistry panels: Evaluating the utility of four-protein versus two-protein panels in endometrial cancer patients

This study aimed to assess the accuracy of a two-protein panel for mismatch repair (MMR) immunohistochemistry (IHC) compared to a four-protein panel in a cohort of endometrial cancer patients. The study included patients diagnosed with endometrial cancer between January 2018 and December 2023 with patients underwent MMR IHC staining for the four-protein panel (MSH2, MSH6, MLH1, and PMS2) serving as the reference standard. Various combinations of two proteins were examined and evaluated for their accuracy against the four-protein panel. Sensitivity, negative predictive value (NPV), and negative likelihood ratio were calculated for each combination. McNemar's test was performed to assess discordance, and receiver operating characteristic (ROC) curves were generated to evaluate diagnostic accuracy. Of 593 patients, MMR deficiency defined as at least one protein loss was observed in 146 patients (24.62%). When compared with four-protein panel, the highest sensitivity was observed with the MSH6/PMS2 combination (99.32%), followed sequentially by MSH6/MLH1 (97.26%), MSH2/PMS2 (93.15%), MSH2/MLH1 (91.10%), MLH1/PMS2 (79.45%), and MSH2/MSH6 (21.92%). The MSH6/PMS2 combination also demonstrated the best NPV of 99.78% and negative likelihood ratio of 0.01, while MSH6/MLH1 showed satisfactory NPV of 99.11% and negative likelihood ratio of 0.03. McNemar's test revealed no statistical difference between the four-protein panel and the MSH6/PMS2 panel (p = 1.000), and the MSH6/MLH1 panel (p = 0.125). The two-protein panel, particularly MSH6/PMS2, offers high sensitivity and negative predictive value, suggesting its potential as a cost-effective alternative to the four-protein panel in MMR testing for endometrial cancer patients.

Molecular Interplay Between PTEN, ARID1A, PD-L1, and MMR in Asian Ovarian Clear Cell Carcinoma: Implications for Immunotherapy Response and Patient Stratification

Ovarian clear cell carcinoma (OCCC) represents a distinct histological subtype with a high prevalence in Asian populations and poor chemotherapy response. This study investigated molecular interactions between phosphatase and tensin homolog (PTEN), AT-rich interactive domain 1A (ARID1A), programmed death-ligand 1 (PD-L1), and mismatch repair (MMR) proteins in Asian patients with OCCC. Immunohistochemical analysis was performed on tissue microarrays from 69 OCCC cases. The expression of PTEN, ARID1A, PD-L1, and four MMR proteins was evaluated alongside clinical data. A high prevalence of PTEN loss (78.3%) and ARID1A deficiency (48.8%), with PD-L1 expression in 26.1% and MMR deficiency in 10.1% of cases, was observed. All PD-L1-positive tumors demonstrated concurrent PTEN loss (p = 0.007). MMR deficiency was significantly associated with ARID1A loss (p = 0.049). PTEN loss correlated with worse progression-free survival (PFS) in early-stage disease (p = 0.039). PTEN and ARID1A alterations represent early pathogenic events in Asian OCCC, with PTEN loss significantly impacting PFS in early-stage disease. The correlation between PTEN loss and PD-L1 expression, alongside ARID1A-MMR deficiency association, provides insights into OCCC’s immunological landscape and therapeutic vulnerabilities.