Objective: To examine the efficacy of MSH6 and PMS2 immunohistochemistry (IHC) as a screening method for Lynch syndrome in endometrial cancer patients. Methods: Through multidisciplinary discussions, an institutional MSH6 and PMS2 IHC-initiated cascade test (MSH6, PMS2 IHC→microsatellite instability [MSI] assay→germline mismatch repair [MMR] gene sequencing) was developed to screen for Lynch syndrome in endometrial cancer patients. Testing was performed on a consecutive cohort of 218 newly diagnosed endometrial cancer patients who underwent surgery at a tertiary hospital in the Republic of Korea between August 2018 and December 2020. The number of MMR deficiencies (MSH6 or PMS2 loss in IHC) and results of subsequent tests (MSI assay and germline MMR gene sequencing) were examined. Results: MMR deficiency was detected in 52 of the 218 patients (24.0%). Among these 52 patients, 34 (65.0%) underwent MSI testing, of which 31 (91.0%) exhibited high MSI. Of the 31 patients with MSI-high status, 15 (48.0%) underwent germline MMR gene sequencing. Subsequently, Lynch syndrome was diagnosed in five patients (33.0%). Conclusion Lynch syndrome screening using MSH6 and PMS2 IHC-initiated cascade testing is a viable strategy in the management of endometrial cancer. A simplified strategy (MSH6 and PMS2 IHC→germline MMR gene sequencing) was proposed because most women with MMR deficiencies exhibited high MSI.

Purpose: Since tumor mutational burden (TMB) and gene expression profiling (GEP) have complementary effects, they may have improved predictive power when used in combination. Here, we investigated the ability of TMB and GEP to predict the immunotherapy response in patients with non–small cell lung cancer (NSCLC) and assessed if this combination can improve predictive power compared to that when used individually. Materials and Methods: This retrospective cohort study included 30 patients with NSCLC who received immune checkpoint inhibitors (ICI) therapy at the Seoul National University Bundang Hospital. programmed cell death-ligand-1 (PD-L1) protein expression was assessed using immunohistochemistry, and TMB was measured by targeted deep sequencing. Gene expression was determined using NanoString nCounter analysis for the PanCancer IO360 panel, and enrichment analysis were performed. Results: Eleven patients (36.7%) showed a durable clinical benefit (DCB), whereas 19 (63.3%) showed no durable benefit (NDB). TMB and enrichment scores (ES) showed significant differences between the DCB and NDB groups (p=0.044 and p=0.017, respectively); however, no significant correlations were observed among TMB, ES, and PD-L1. ES was the best single biomarker for predicting DCB (area under the curve [AUC], 0.794), followed by TMB (AUC, 0.679) and PD-L1 (AUC, 0.622). TMB and ES showed the highest AUC (0.837) among other combinations (AUC [TMB and PD-L1], 0.777; AUC [PD-L1 and ES], 0.763) and was similar to that of all biomarkers used together (0.832). Conclusion The combination of TMB and ES may be an effective predictive tool to identify patients with NSCLC patients who would possibly benefit from ICI therapies.

Objective: The need to perform genetic sequencing to diagnose the polymerase epsilon exonuclease (POLE) subtype of endometrial cancer (EC) hinders the adoption of molecular classification. We investigated clinicopathologic and protein markers that distinguish the POLE from the copy number (CN)-low subtype in EC. Methods: Ninety-one samples (15 POLE, 76 CN-low) were selected from The Cancer Genome Atlas EC dataset. Clinicopathologic and normalized reverse phase protein array expression data were analyzed for associations with the subtypes. A logistic model including selected markers was constructed by stepwise selection using area under the curve (AUC) from 5-fold cross-validation (CV). The selected markers were validated using immunohistochemistry (IHC) in a separate cohort. Results: Body mass index (BMI) and tumor grade were significantly associated with the POLE subtype. With BMI and tumor grade as covariates, 5 proteins were associated with the EC subtypes. The stepwise selection method identified BMI, cyclin B1, caspase 8, and X-box binding protein 1 (XBP1) as markers distinguishing the POLE from the CN-low subtype. The mean of CV AUC, sensitivity, specificity, and balanced accuracy of the selected model were 0.97, 0.91, 0.87, and 0.89, respectively. IHC validation showed that cyclin B1 expression was significantly higher in the POLE than in the CN-low subtype and receiver operating characteristic curve of cyclin B1 expression in IHC revealed AUC of 0.683. Conclusion BMI and expression of cyclin B1, caspase 8, and XBP1 are candidate markers distinguishing the POLE from the CN-low subtype. Cyclin B1 IHC may replace POLE sequencing in molecular classification of EC.

Objective: We evaluated droplet digital polymerase chain reaction (ddPCR) method for detecting POLE mutations in endometrial cancer (EC) and guiding its molecular classification. Methods: We reviewed 240 EC specimens from our hospital database. A ddPCR assay was used to identify POLE mutations at 5 known hotspots (P286R, S297F, V411L, A456P, and S459F). Expressions of p53 and mismatch repair proteins were identified using immunohistochemistry. Results: The ddPCR assay identified POLEmutations in 10.8% of patients. The most common mutation was V411L (61.54%), followed by P286R (23.07%), S459F (7.69%), S297F (3.85%), and A456P (3.85%). Eight/one cases had positive ddPCR but negative Sanger sequencingext-generation sequencing, respectively. Molecular classification revealed p53-mutated subtype as significantly more common for tumors with a high International Federation of Gynecology and Obstetrics (FIGO) grade, deep myometrial invasion, lymphovascular space invasion, advanced stage, and high/advanced risk groups; the POLE mutated group was more frequent in the low stage and low/intermediate risk group. Survival analyses revealed the poorest outcomes for p53-mutated EC, while mismatch repair-deficient and no specific molecular profile ECs had similar progression-free survival (PFS) outcomes, and POLE -mutated ECs had the best PFS outcome (p<0.001). When only intermediate, high-intermediate, and high-risk groups were analyzed for subgroups, molecular classification still showed differences both in PFS (p=0.003) and overall survival (p=0.017). Conclusion Hotspot POLE mutations can be detected using the ddPCR assay. We suggest simultaneously evaluating POLE mutation status using ddPCR and p53/mismatch repair protein expressions using immunohistochemistry, which can rapidly and accurately determine the molecular subtype of EC.

Purpose: The impact of conversion on perioperative and long-term oncologic outcomes is controversial. Thus, we compared these outcomes between laparoscopic (Lap), unplanned conversion (Conversion), and planned open (Open) liver resection for hepatocellular carcinoma (HCC) located in anterolateral (AL) liver segments and aimed to identify risk factors for unplanned conversion. Methods: We retrospectively studied 374 patients (Lap, 299; Open, 62; Conversion, 13) who underwent liver resection for HCC located in AL segments between 2004 and 2018. Results: Compared to the Lap group, the Conversion group showed greater values for operation time (p < 0.001), blood loss (p = 0.021), transfusion rate (p = 0.009), postoperative complication rate (p = 0.008), and hospital stay (p = 0.040), with a lower R0 resection rate (p < 0.001) and disease-free survival (p = 0.001). Compared with the Open group, the Conversion group had a longer operation time (p = 0.012) and greater blood loss (p = 0.024). Risk factors for unplanned conversion were large tumor size (odds ratio [OR], 1.35; 95% confidence interval [CI], 1.05–1.74; p = 0.020), multiple tumors (OR, 5.95; 95% CI, 1.45–24.39; p = 0.013), and other organ invasion (OR, 15.32; 95% CI, 1.80–130.59; p = 0.013). Conclusion In conclusion, patients who experienced unplanned conversion during LLR for HCC located in AL segments showed poor perioperative and long-term outcomes compared to those who underwent planned laparoscopic and open liver resection. Therefore, open liver resection should be considered in patients with risk factors for unplanned conversion.

The long-term survival of heavily pretreated patients with primary peritoneal cancer (PPC) is uncommon. Here, we report on a patient with PPC refractory to multiple lines of intravenous chemotherapy, namely, a combined regimen of paclitaxel and carboplatin, and single regimens of topotecan, docetaxel, cisplatin, and gemcitabine. However, after intraperitoneal (IP) chemotherapy with paclitaxel-cisplatin, the patient's condition improved, and she has been progression-free for more than 4 years. Interestingly, before the IP chemotherapy, the recurrences were limited to the peritoneal cavity. These results suggest that IP recurrence might be a predictor of a good response to IP chemotherapy.
Carboplatin ; Cisplatin ; Drug Therapy ; Humans ; Infusions, Parenteral ; Neoplasm Recurrence, Local ; Ovarian Neoplasms ; Paclitaxel ; Peritoneal Cavity ; Peritoneal Neoplasms ; Recurrence ; Topotecan

Most cases of congenital hyperthyroidism are autoimmune forms caused by maternal thyroid stimulating antibodies. Nonautoimmune forms of congenital hyperthyroidism caused by activating mutations of the thyrotropin receptor (TSHR) gene are rare. A woman gave birth to a boy during an emergency cesarean section at 33 weeks of gestation due to fetal tachycardia. On the 24th day of life, thyroid function tests were performed due to persistent tachycardia, and hyperthyroidism was confirmed. Auto-antibodies to TSHR, thyroid peroxidase, and thyroglobulin were not found. The patient was treated with propylthiouracil and propranolol, but hyperthyroidism was not well controlled. At 3 months of age, the patient had craniosynostosis and hydrocephalus, and underwent a ventriculoperitoneal shunt operation. Direct sequencing of the TSHR gene showed a heterozygous mutation of c.1899C>A (p.Asp633Glu) in exon 10. No mutations were discovered in any of the parents in a familial genetic study. We have reported a case of sporadic nonautoimmune congenital hyperthyroidism, by a missense mutation of the TSHR gene, for the first time in South Korea.
Cesarean Section ; Craniosynostoses ; Emergencies ; Exons ; Female ; Germ-Line Mutation ; Humans ; Hydrocephalus ; Hyperthyroidism* ; Immunoglobulins, Thyroid-Stimulating ; Iodide Peroxidase ; Korea ; Male ; Mutation, Missense ; Parents ; Parturition ; Pregnancy ; Propranolol ; Propylthiouracil ; Receptors, Thyrotropin ; Tachycardia ; Thyroglobulin ; Thyroid Function Tests ; Ventriculoperitoneal Shunt

BACKGROUND: Superficial dermatomycoses are fungal infections of the skin, hair, or nails and are most commonly caused by dermatophytes. Superficial dermatomycoses are very common diseases in the field of dermatology; however, their prevalence and clinical characteristics vary with geographical areas and populations. Moreover, pathogenic species change constantly over time. OBJECTIVE: This multicenter study aimed to investigate the epidemiologic and clinical findings of tinea corporis, tinea faciale, and tinea capitis in Korea during 2016-2017. In addition, we sought to identify the pathogenic organism causing these three different types of fungal infections. METHODS: Total 453 patients from the dermatology clinics of 13 tertiary hospitals in Korea were enrolled in this study. Information regarding demographic characteristics, comorbidities, occupation, family history of superficial dermatomycoses, suspected routes of infection, and treatment was collected. Fungal cultures and molecular analyses were performed for patients with tinea corporis, tinea faciale, and tinea capitis. RESULTS: Of the 453 patients, 275 were men and 178 were women. With respect to past history, 214 patients (53.4%) had at least one comorbidity. Tinea corporis (27.3%) was the most common form of superficial dermatomycosis, followed by tinea pedis (23.2%) and tinea unguium (16.6%). Overall, the fungal culture positivity was 77.8% (126/162). Trichophyton rubrum was the most common causative organism for tinea corporis (66.7%, 68/80) and tinea faciale (43.8%, 14/23), while Microsporum canis was the most common causative organism for tinea capitis (36.7%, 11/23). CONCLUSION Trichophyton rubrum was consistently the most common causative organism of superficial dermatomycoses, except for tinea capitis in Korea.

BACKGROUND: There have been several therapeutic guidelines for onychomycosis in different countries and advances in its diagnosis and treatment. Optimal treatment decision-making is affected by healthcare systems and cultural backgrounds of countries. OBJECTIVE: The executive committee for onychomycosis guideline of the Korean Society for Medical Mycology aims to provide up-to-date practical guidelines for onychomycosis management in Koreans. METHODS: The committee thoroughly reviewed relevant literature and previous guidelines. The structured algorithmic guideline was developed by experts' consensus. RESULTS: The optimal treatments can be selected alone or in combination based on the nail and patient variables. Three major classes of treatment are available: standard (topical or oral antifungals), additional (nail removal), and alternative treatments (laser). Both topical and oral antifungals alone are appropriate for mild onychomycosis, while oral antifungals are primarily recommended for moderate-to-severe cases if not contraindicated. Combined topical and oral antifungals are recommended to increase the efficacy in moderate-to-severe cases. Additional infected nail removal is also considered for moderate-to-severe onychomycosis, which is unresponsive to standard medical treatment alone. Laser therapy can be an alternative without significant side effects when standard medical treatments cannot be applied regardless of onychomycosis severity. After treatment course completion, periodic therapeutic response monitoring and onychomycosis preventive measures should be rendered to reduce recurrence. CONCLUSION The Korean consensus guideline provides evidence-based recommendations to promote good outcomes of onychomycosis. The proposed algorithm is simple and easy to comprehend, allowing clinicians to facilitate optimal treatment decision-making for onychomycosis in clinical practice.

Pseudohypoparathyroidism (PHP) is a rare disorder caused by genetic and epigenetic aberrations in the GNAS complex locus resulting in impaired expression of stimulatory G protein (Gsα). PHP type Ib (PHP-Ib) is characterized by hypocalcemia and hyperphosphatemia due to renal resistance to the parathyroid hormone, and is distinguished from PHP-Ia by the absence of osteodystrophic features. An 11-yr-old boy presented with poor oral intake and cramping lower limb pain after physical activity. Laboratory studies revealed hypocalcemia, hyperphosphatemia, and increased parathyroid hormone levels. The GNAS complex locus was evaluated using the methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA) assay. Gain of methylation in the NESP55 domain and loss of methylation in the antisense (AS) transcript, XL, and A/B domains in the maternal allele were observed. Consequently, we present a case of PHP-Ib diagnosed using MS-MLPA.
Alleles ; Epigenomics ; GTP-Binding Proteins ; Humans ; Hyperphosphatemia ; Hypocalcemia ; Lower Extremity ; Male ; Methylation* ; Motor Activity ; Multiplex Polymerase Chain Reaction ; Muscle Cramp ; Parathyroid Hormone ; Pseudohypoparathyroidism*