The study was to evaluate the prevalence of mismatch repair gene defect among Thai patients with endometrial cancer and its association with clinico-pathological features and survivals. The formalin fixed paraffin-embedded blocks of EMC tissue from hysterectomy specimens of patients having surgery in our institution between 1 Jan 1995 and 31 December 2016 were assessed for the immunohistochemical expression of 4 mismatch repair proteins (MLH1, PMS, MSH2, MSH 6). Mismatch repair gene defect was determined by a negative expression of at least 1 protein. Among 385 EMC patients included in the study, mean age was 57.3 ± 10.8 years with 62.3% aged ⩽ 60 years. The most frequent mismatch repair gene defect was MSH6 (38.7%), followed by PMS2 (34.3%), MLH1 (33.2%), and MSH2 (16.4%). Overall, 55.1% showed negative expression of at least one protein. We found significantly higher mismatch repair gene defect in patients aged ⩽ 60 years, with early stage disease, and negative lymph node status than the other comparative groups: 59.2% vs 48.3% for age (p = 0.037), 58.2% vs 45.2% (p = 0.027) for stage, and 58.1% vs 44.6% (p = 0.048) for nodal status. The 5-year progression-free survival, overall survival, and endometrial cancer-specific survival of patients with mismatch repair gene defect was higher than those without gene defect. The differences were statistically significant for only progression-free survival and endometrial cancer-specific survival: 87.7% (95% confidence interval = 83.0%-92.4%) vs 81.5% (95% confidence interval = 75.4%-87.6%) (p = 0.049) for progression-free survival and 91.0% (95% confidence interval = 86.9%-95.1%) vs 85.5% (95% confidence interval = 80.0%-91.0%) (p = 0.044) for endometrial cancer-specific survival, respectively. In conclusion, more than half of Thai endometrial cancer patients had mismatch repair gene defect. The patients with mismatch repair gene defect had significantly younger age (⩽ 60 years) and better prognosis in terms of early stage, negative nodal status, and longer survivals.
Introduction: National License Examination (NLE) is organized by the Consortium of Thai Medical Schools to assess the competency of medical students. Part I-NLE involves an evaluation of basic science knowledge. Our objective was to evaluate factors associated with the results of part-I NLE. Methods: Learning attitude and behavior, preparation for and attitude towards the NLE were surveyed by a questionnaire given to all third to fifth year students (in 2010) at the institution. Additional data collected were: gender, admission and aptitude tests scores, cumulative grade point average (GPA) during the first two years, and the results of part-I NLE. Association of these factors and the results of the examination were studied. Results: Mean age of 206 participants was 21.1 + 0.74 years. 55% were female 45% male. Mean aptitude and admission scores were 18.9 + 2.64 and 51.4 ± 8.75, respectively while mean of GPA was 3.0 ± 0.33. From the questionnaire: mean scores of learning behavior, preparation and attitude towards the NLE were 3.3 ± 0.40, 3.1 ± 0.57, and 3.3 ± 0.61, respectively. There were174/ 206 students who passed the NLE. Factors significantly associated with achievement were: good GPA > 3.0, good learning behaviors (score > 3.0), and good preparation for the examination (score > 3.2). Conclusions: Recent academic effort and performance (represented as GPA and behaviors in learning and preparation for the examination) were more important than remote academic background (represented as aptitude and admission scores).Medical teachers should stimulate students to have continuous effort in learning and preparation for the examination.
Objective: To determine any association between expression of estrogen receptor (ER), progesterone receptor (PR), and Her-2/neu and clinicopathological features, including survival, of endometrial carcinoma (EMC) patients. Methods: Samples of formalin-fixed, paraffin-embedded tissue of 108 patients with EMC treated at our institution between January 1994 and December 2007 were immunohistochemically studied. Results: ER, PR, and Her-2/neu expression were positive in 59.3%, 65.7% and 2.8% of cases, respectively. Positive ER expression was significantly associated with grade I-II tumor while PR expression was linked with endometrioid histology, grade I-II tumor, less myometrial invasion (MI) and negative lymph node involvement. Her-2/neu expression was significantly associated with deep MI, while positive ER and negative Her-2/neu expression in combination was significantly associated with longer disease-free and overall survival. Conclusion: ER expression is a good prognostic factor while Her-2/neu expression appears to be a poor indicator for both disease-free and overall survival, while PR tended to show favorable influence for only disease-free survival of Thai EMCs.
Background: Although immune checkpoint inhibitors against programmed death-1 (PD-1) and its ligand (PD-L1) have demonstrated promising results in several solid malignancies, including cervical cancer, there are some limitations to using PD-L1 immunohistochemical expression as a predictive biomarker for selecting patients who may benefit from such therapy.Objective: To examine the protein expression and genetic status of PD-L1 with clinical outcomes in locally advanced cervical cancer. Methods:We investigated the PD-L1 gene copy number gains assessed by fluorescence in situ hybridization (FISH) and PD-L1 expression using immunohistochemistry in 123 patients with locally advanced cervical cancers between December 2008 and December 2016. Results:The prevalence of PD-L1 immunohistochemical expression was detected in 103/123(83%) cases. PD-L1 gene amplification and polysomy were detected in 7% and 40% of cases, respectively. PD-L1 gene amplification and polysomy were associated with positive PD-L1 immunostaining (score 1+ to 3+) in 88% and 68% of cases, respectively. Clinically, PD-L1 immunopositivity was associated with parametrial invasion at diagnosis. In contrast, PD-L1 polysomy was associated with parametrial invasion and FIGO stages III-IV, whereas PD-L1 amplification was associated with nodal metastasis. In multivariate analysis, PD-L1 amplification was predictive of worse RFS (HR, 5.68; 95%CI,; p = 0.001), whereas PD-L1 polysomy was predictive of worse LRR (HR, 4.13; 95%CI,; p = 0.003). PD-L1 immunohistochemical expression was not associated with worse outcomes in Cox models. Conclusions:Our results showed that an increase in PD-L1 gene copy number could be a novel prognostic and possible predictive biomarker for anti-PD-1/PD-L1 therapy in locally advanced cervical cancer.
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