BACKGROUND: The gene for chromodomain helicase/ATPase DNA binding protein 1-like (CHD1L) was recently identified as a target oncogene within the 1q21 amplicon, which occurs in 46% to 86% of primary hepatocellular carcinoma (HCC) cases. However, the prognostic significance of CHD1L in HCC remains uncertain. In this study, we investigated the roles of CHD1L in the prognosis of HCC. METHODS: We investigated the expressions of CHD1L in tumor tissue microarrays of 281 primary HCC patients who underwent surgical resection using immunohistochemistry. Prognostic factors of HCC were examined by univariate and multivariate analyses. The median follow-up period was 75.6 months. RESULTS: CHD1L expression was observed in 48 of the 281 HCCs (17.1%). CHD1L expression was associated with a younger age (p=0.033), higher Edmondson grade (p=0.019), microvascular invasion (p<0.001), major portal vein invasion (p=0.037), higher American Joint Committee on Cancer T stage (p=0.001), lower albumin level (p=0.047), and higher alpha-fetoprotein level (p=0.002). Multivariate analyses revealed that CHD1L expression (p=0.027), Edmondson grade III (p=0.034), and higher Barcelona Clinic Liver Cancer stage (p<0.001) were independent predictors of shorter disease-free survival. CONCLUSIONS: CHD1L expression might be a prognostic marker of shorter disease-free survival in HCC patients after surgical resection.
alpha-Fetoproteins ; Carcinoma, Hepatocellular ; Disease-Free Survival ; DNA-Binding Proteins ; Follow-Up Studies ; Humans ; Immunohistochemistry ; Joints ; Liver Neoplasms ; Multivariate Analysis ; Oncogenes ; Portal Vein ; Prognosis

BACKGROUND/AIMS: The prognosis after surgical resection of hepatocellular carcinoma (HCC) remains poor because of a high rate of recurrence. Thus, it is crucial to identify patients with a high risk of recurrence after curative hepatectomy and to develop more effective and targeted treatment strategies to improve disease outcomes. In this study, we investigated the roles of metadherin (MTDH) in the prognosis of HCC. METHODS: We investigated MTDH expression using immunohistochemistry in tumor tissue microarrays of 288 primary HCC patients who underwent curative surgical resection. RESULTS: High MTDH expression was observed in 138 of the 288 HCC cases (47.9%). High MTDH expression was associated with a younger age (p<0.001), higher Edmondson grade (p<0.001), microvascular invasion (p<0.001), higher American Joint Committee on Cancer T stage (p=0.001), and higher alpha-fetoprotein level (p=0.003). Multivariate analyses revealed that high MTDH expression (p=0.014), higher Barcelona-Clinic Liver Cancer (BCLC) stage (p<0.001), and Edmondson grade III (p=0.042) were independent predictors of shorter disease-free survival (DFS). Higher BCLC stage (p<0.001) and Edmondson grade III (p=0.047) were also independent predictors of shorter disease-specific survival. CONCLUSIONS: High MTDH expression may be a prognostic predictor of shorter DFS in HCC patients after curative hepatectomy.
alpha-Fetoproteins ; Carcinoma, Hepatocellular ; Disease-Free Survival ; Hepatectomy ; Humans ; Immunohistochemistry ; Joints ; Liver Neoplasms ; Multivariate Analysis ; Prognosis ; Recurrence

Progressive familial intrahepatic cholestasis (PFIC) is a group of rare genetic disorders caused by defects in biliary epithelial transporters. It mostly presents as low γ-glutamyltransferase cholestasis. Recently, USP53 has been identified as one of the novel genes associated with PFIC. Herein, we report a 21-year-old Korean male patient with a late-onset PFIC. Initial work-up, including whole genome sequencing, did not find any associated gene. However, reviewing sequencing data identified novel compound heterozygous variants in splicing site of USP53 (NM_001371395.1:c.972+3_972+6del, and c.973-1G>A). The patient’s bilirubin level fluctuated during the disease course. At 4.5 years after the initial presentation, the patient’s symptom and high bilirubin level were normalized after administration of high-dose ursodeoxycholic acid. Recognition of this disease entity is important for prompt diagnosis and management. USP53 is recommended for the work-up of low γ-glutamyltransferase cholestasis.

Background: Uric acid (UA) has been suggested as a possible biomarker of bipolar disorder (BD) in recent studies. We aimed to provide a clearer comparison of UA levels between BD and major depressive disorder (MDD). Methods: We retrospectively reviewed the medical chart records of psychiatric inpatients aged 19–60 years, whose main discharge diagnoses were either MDD or BD, with an admission between January 1, 2015 and December 31, 2018 at Seoul National University Hospital. Data such as sex, age, body mass index (BMI), medication usage, and serum UA levels were extracted. Patients with medical conditions or on medications that could influence UA levels were excluded. Age, sex, BMI, and psychiatric drug usage were considered in the comparison of serum UA between MDD and BD patients. Results: Our sample consisted of 142 MDD patients and 234 BD patients. The BD patients had significantly higher serum UA levels compared to the MDD patients, without accounting for other confounding variables (5.75 ± 1.56 mg/dL vs. 5.29 ± 1.59 mg/dL, P = 0.006). T-test comparisons between psychiatric medication users and non-users revealed that mood stabilizers and antipsychotics may be relevant confounding factors in our sample analysis. The likelihood of BD diagnosis was significantly correlated with higher UA levels (odds ratio, 1.410; 95% confidence interval, 1.150–1.728; P = 0.001) when accounting for sex, age, and BMI in the logistic regression analysis. Also, accounting for mood stabilizers or antipsychotics, the likelihood of BD diagnosis was still significantly correlated with higher UA levels. Conclusion Our study confirms that BD patients are significantly more likely to show higher serum UA levels than MDD patients. The high UA levels in BD point to purinergic dysfunction as an underlying mechanism that distinguishes BD from MDD. Further research is recommended to determine whether UA is a trait or a state marker and whether UA correlates with the symptoms and severity of BD.

Human epidermal growth factor receptor 2 (HER2) protein overexpression and/or HER2 gene amplification is found in about 20% of invasive breast cancers. It is a sole predictive marker for treatment benefits from HER2 targeted therapy and thus, HER2 testing is a routine practice for newly diagnosed breast cancer in pathology. Currently, HER2 immunohistochemistry (IHC) is used for a screening test, and in situ hybridization is used as a confirmation test for HER2 IHC equivocal cases. Since the American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) guidelines on HER2 testing was first released in 2007, it has been updated to provide clear instructions for HER2 testing and accurate determination of HER2 status in breast cancer. During HER2 interpretation, some pitfalls such as intratumoral HER2 heterogeneity and increase in chromosome enumeration probe 17 signals may lead to inaccurate assessment of HER2 status. Moreover, HER2 status can be altered after neoadjuvant chemotherapy or during metastatic progression, due to biologic or methodologic issues. This review addresses recent updates of ASCO/CAP guidelines and factors complicating in the interpretation of HER2 status in breast cancers.

BACKGROUND: Malignant mesothelioma of the pleura is an aggressive tumor known to be associated with asbestos. Histological diagnosis of mesothelioma is challenging and is usually aided by immunohistochemical markers. METHODS: During an 18-year period (1995-2012), 66 patients with pleural mesothelioma were diagnosed at the Samsung Medical Center in Seoul. We reviewed hematoxylin and eosin and immunohistochemical slides of pleural mesothelioma and evaluated their pathological and clinical features. RESULTS: The male-to-female ratio was 1.75:1, and age of patients ranged from 28 to 80 years with an average age of 56.84 years. Twenty-two out of 66 patients underwent curative pneumonectomy. Follow-up data was available in 60 patients (90.9%), and 50 of them (83.3%) died from the disease. The average overall survival was 15.39 months. Histologically, the epithelioid type was the most common, followed by the sarcomatoid and the biphasic types. Epidemiologic information was not available in most cases, and only one patient was confirmed to have a history of asbestos exposure. CONCLUSIONS: Malignant mesothelioma of the pleura is a fatal tumor, and the therapeutic benefit of pneumonectomy remains unproven. The combination of calretinin, Wilms tumor 1, HMBE-1, and thyroid transcription factor-1 may provide high diagnostic accuracy in diagnosing mesothelioma.
Asbestos ; Calbindin 2 ; Diagnosis ; Eosine Yellowish-(YS) ; Follow-Up Studies ; Hematoxylin ; Humans ; Immunohistochemistry ; Mesothelioma* ; Pleura ; Pneumonectomy ; Seoul ; Thyroid Gland ; Wilms Tumor

BACKGROUND: BCL9 enhances beta-catenin-mediated transcriptional activity regardless of the mutational status of the Wnt signaling components and increases the cell proliferation, migration, invasion, and metastatic potential of tumor cells. The goal of this study was to elucidate the prognostic significance of BCL9 protein expression in hepatocellular carcinoma (HCC) patients. METHODS: We evaluated BCL9 protein expression by immunohistochemistry in tumor tissue from 288 primary HCC patients who underwent curative hepatectomy. The impact of BCL9 expression on the survival of the patients was analyzed. The median follow-up period was 97.1 months. RESULTS: Nuclear BCL9 protein expression was observed in 74 (25.7%) of the 288 HCCs. BCL9 expression was significantly associated with younger age (p=0.038), higher Edmondson grade (p=0.001), microvascular invasion (p=0.013), and intrahepatic metastasis (p=0.017). Based on univariate analyses, BCL9 expression showed an unfavorable influence on both disease-free survival (DFS, p=0.012) and disease-specific survival (DSS, p=0.032). Multivariate analyses revealed that higher Barcelona Clinic Liver Cancer stage was an independent predictor of both shorter DFS (p<0.001) and shorter DSS (p<0.001). BCL9 expression tended to be an independent predictor of shorter DFS (p=0.078). CONCLUSIONS: BCL9 protein expression might be a marker of shorter DFS in HCC patients after curative hepatectomy.
Carcinoma, Hepatocellular ; Cell Proliferation ; Disease-Free Survival ; Follow-Up Studies ; Hepatectomy ; Humans ; Immunohistochemistry ; Liver Neoplasms ; Multivariate Analysis ; Neoplasm Metastasis ; Recurrence

No abstract available.
Hemangioma*

Metastatic tumors to the hand are rare and often overlooked by clinicians. Here, we report a rare case of phalangeal metastasis of right 4th finger in a patient with hepatocellular carcinoma. Treatment was given with right 4th finger disarticulation. This report suggests that physicians must take consideration into the possibility of metastatic tumors in patients with bone lesions on hands and a history of malignancy.
Carcinoma, Hepatocellular ; Disarticulation ; Fingers ; Hand ; Humans ; Neoplasm Metastasis

BACKGROUND: Thymic neuroendocrine carcinomas (NECs) are uncommon, for which there is no established information available because of a limited number of epidemiological study in Asia. METHODS: We reviewed 21 cases of surgically resected thymic NECs, and evaluated their pathological and clinical features. RESULTS: It showed male predominance (male/female ratio, 15/6) with wide age range from 20 to 72 years (mean age, 49 years). All 21 cases were divided into two types according to the World Health Organization criteria: atypical carcinoid (n=18) and large cell NEC (n=3). Three cases of atypical carcinoid (AC) were associated with ectopic Cushing's syndrome. All the patients (3/3) with large cell NEC (3/3) and 16.7% (3/18) of those with AC died of tumor progression. Common sites of metastasis included lung, lymph node, brain, lumbar spine, mediastinum, bone, and liver. CONCLUSIONS: In conclusion, thymic neuroendocrine tumors carry a poor prognosis. Regarding the tumor classification, our results showed that a vast majority of carcinoids in the thymus correspond to ACs. In addition, our results also indicate that typical carcinoid is a very rare entity. Some cases of AC exhibited a large size, solid pattern and they showed aggressive clinical behavior, which highlights the spectrum of histologic appearances of thymic NECs.
Female ; Male ; Humans ; Neoplasm Metastasis