Eun Su Park

Cancer-Testis Antigen Expression in Serous Endometrial Cancer with Loss of X Chromosome Inactivation

Background Cancer-testis antigens (CTAs) are potential targets for cancer immunotherapy. Many CTAs are located on the X chromosome and are epigenetically regulated. Loss of X chromosome inactivation (XCI) is observed in breast and ovarian cancers and is thought to be related to the overexpression of CTAs. We investigated the relation between expression of CTAs and loss of XCI in endometrial cancer. Materials and Methods We used data generated by The Cancer Genome Atlas Genome Data Analysis Centers and data for Xist knockout mice available at the Gene Expression Omnibus. Results The status of XCI was estimated by methylation status, and deletion or gain of the X chromosome. The endometrial cancers were classified into the following three groups: preserved inactivated X chromosome (Xi) (n = 281), partial reactivation of Xi (n = 52), and two copies of active X group (n = 38). Loss of XCI was more common in serous adenocarcinoma. Expression of CTAs increased in endometrial cancer with loss of XCI, which was accompanied by global hypomethylation. Expression of CTAs did not increase in Xist knockout mice. Conclusions Loss of XCI is common in serous adenocarcinoma. Global hypomethylation, and not loss of XCI, is the main mechanism of overexpression of CTAs.

Diagnostic Usefulness of Real-Time Elastography for Liver Fibrosis in Chronic Viral Hepatitis B and C

The aim of this study was to investigate the diagnostic usefulness of real-time elastography (RTE) for liver fibrosis in chronic viral hepatitis B (CHB) and C (CHC). Fifty-one and thirty-two of the patients were diagnosed with CHB and CHC, respectively. Enrolled patients underwent liver biopsy and RTE. The FIB-4 index and aspartate transaminase-to-platelet ratio index (APRI) were also measured. The liver fibrosis index (LFI) by RTE increased significantly with the Knodell fibrosis stage: 3.14 ± 0.62 for F0, 3.28  ±  0.42 for F1, 3.43  ±  0.53 for F3, and 4.09  ±  1.03 for F4 (P = 0.000). LFI as well as APRI, FIB-4, platelet, albumin, and prothrombin time showed the difference in patients with advanced fibrosis (≥F3) and those with mild fibrosis (≤F1). In addition, RTE had better discrimination power between ≥F3 and F4 than between FIB-4 and APRI. In CHC patients, the area under receiver operating characteristic curves of RTE for advanced fibrosis was higher than that in CHB patients (0.795 versus 0.641). RTE is useful for the assessment of advanced fibrosis in patients with CHB and CHC and has better discrimination power than other serologic markers.

Glomangiopericytoma and glomus tumor of the sinonasal tract: A report of two cases with emphasis on the differential diagnosis

To the Editor Glomangiopericytoma (GPC; also known as sinonasal typehemangiopericytoma) is very rare, comprising <0.5% of sinonasal tumors. It belongs to the category of borderline and low malignant potential tumors of soft tissues in the nose and paranasal sinuses according to the World Health Organization. GPCs show true pericytic myoid differentiation with consistent expression of smooth muscle actin (SMA). Glomus tumors (GTs) are benign mesenchymal neoplasms and usually originate in the glomus bodies, which are abundant in the distal extremities. GTs of the nose and paranasal sinus are extremely rare. To our knowledge, no more than 30 cases occurring in the sinonasal tract have been reported in the literature. Some authors have speculated a possible relationship between GPC and GT. A previous study reported that GPC is biologically close or identical toGTbased on the striking similarities in the histological appearances and immunophenotypes of these tumors. Recently, it was proposed that mutational activation of beta-catenin and the associated overexpression of cyclin D1 may be key events in the pathogenesis of GPC. Additionally, nuclear accumulation of beta-catenin is a diagnostic marker for GPC and can be a useful discriminator. Here, we report one case each of GPC andGT of the sinonasal tract, and compare their clinicopathologic and immunohistochemical findings.

Comparison of the Cobas 4800 HPV and HPV 9G DNA Chip Tests for Detection of High-Risk Human Papillomavirus in Cervical Specimens of Women with Consecutive Positive HPV Tests But Negative Pap Smears.

Detecting high-risk (HR) HPV is important for clinical management of women with persistent HPV-positive and Pap-negative results. The Cobas 4800 HPV test is the first FDA-approved HPV DNA test that can be used alone as a first-line screening tool. The HPV 9G DNA chip test is a PCR-based DNA microarray assay. We evaluated the patients of consecutive HPV-positivity on HPV 9G DNA chip test without cytologic abnormalities. We then compared the performances of HPV 9G DNA chip and the Cobas 4800 HPV tests for detecting HR HPV with each other and confirmed HPV genotyping using direct sequencing. All 214 liquid-based cytology specimens were collected from 100 women with consecutive HPV-positive and Pap-negative results on the HPV 9G DNA chip test between May 2012 and Dec 2013, but only 180 specimens were available for comparing HPV test results. The HPV 9G DNA chip and the Cobas 4800 HPV tests agreed with each other in 81.7% of the samples, and the concordance rate was greater than 97.2% for detecting HPV-16 or -18. For HR genotypes other than HPV types 16 and 18, the two tests agreed for 81.1% of the samples. The sensitivity of both assays for detecting HR HPV was 100%, regardless of HR genotypes. The HPV 9G DNA chip test may be as effective as the Cobas 4800 HPV test in detecting HR HPV, and has a similar ability to identify HPV-16 and -18.

Clinicopathologic Characteristics and Mutational Status of Succinate Dehydrogenase Genes in Paraganglioma of the Urinary Bladder: A Multi-Institutional Korean Study

CONTEXT - Because of the limited number of available primary bladder paraganglioma (PBPG) cases, the rates of succinate dehydrogenase (SDH) mutations and the clinicopathologic characteristics of SDH-deficient tumors have not been fully studied. OBJECTIVE - To define the clinicopathologic and molecular characteristics of PBPGs. DESIGN - A total of 52 PBPGs were collected retrospectively. SDHA and SDHB immunohistochemical stains were performed. In cases of SDHB expression loss, mutation analyses of SDHB, SDHC, and SDHD were performed. RESULTS - The clinicopathologic features were analyzed for 52 cases (M:F = 27:25), with a mean age of 56 years (range, 22-79 years). Tumor sizes were 0.5 to 8 cm (mean, 2.4 cm). Tumor necrosis was present in 5 of 52 cases (10%), involvement of muscularis propria in 41 (79%), and lymphovascular tumor invasion in 6 (12%). During a mean follow-up period of 41 months (range, 1-161 months), 3 of 52 patients (6%) developed metastases, but no one died from the disease. Immunohistochemistry for SDHA and SDHB showed that all cases were SDHA intact. Among them, 43 cases had intact SDHB, whereas 9 cases were SDHB deficient. Compared with the SDHB-intact cases, the SDHB-deficient cases were characterized by large tumor sizes (4.5 versus 1.9 cm; P < .001), a higher number of mitoses per 10 high-powered fields (2.6 versus 0.1; P = .002), and frequent lymphovascular tumor invasion (33% versus 7%; P = .02) and metastases (22% versus 2%; P = .02). Mutational analyses for SDHB, SDHC, and SDHD were performed in 9 SDHB-deficient cases. Among them, 6 cases were successfully sequenced and revealed SDHB mutations only. CONCLUSIONS - Large tumor size, a higher number of mitoses, and the presence of lymphovascular tumor invasion and SDHB mutations suggest malignant paraganglioma.

Prominent Nucleoli and Non-glandular Feature Are Independent Predictors of PD-L1 Expression in Lung Adenocarcinoma

Background/Aim: In patients with non-small cell lung cancer, relationships between PD-L1 (programmed death-ligand 1) expression and clinicopathological characteristics have been examined. However, the association between cytological features and PD-L1 expression remains unknown. Thus, the aim of this study was to investigate whether nuclear features might be correlated with PD-L1 expression in patients with advanced and inoperable lung adenocarcinoma using small biopsy specimens. Materials and Methods: Archived slides from 90 patients with lung adenocarcinoma who underwent small biopsy between October 2014 and May 2017 at the Incheon St. Marys Hospital, were reviewed. PD-L1 expression was detected by immunohistochemistry using PD-L1 22C3 IHC assay. Associations of PD-L1 expression with pathological and molecular features (EGFR mutation, ALK and ROS-1 rearrangement) were statistically analyzed. Results: PD-L1 expression in tumor cells was positive in 33 of 90 cases (36.7%). Higher PD-L1 expression (≥50%) was more frequent in cases with marked nuclear pleomorphism (p<0.001), coarse chromatin pattern (p=0.006), predominant nucleoli (≥3 μm) (p<0.001), large nuclear diameter (>5× small lymphocyte) (p=0.006), non-glandular feature (p<0.001), and atypical mitosis (p=0.034). There were no significant correlations between PD-L1 positivity and molecular features. In multivariable logistic regression analysis, PD-L1 positivity was independently associated with prominent nucleoli (p=0.005) and non-glandular feature (p=0.007). Conclusion: Prominent nucleoli and non-glandular feature are independent predictors of PD-L1 expression in lung adenocarcinoma.

Characteristics and prognosis of glomangiopericytomas: A systematic review

Glomangiopericytoma belongs to the category of borderline/low‐malignant‐potential tumors of the sinonasal tract, but no studies about prognosis have been reported.

Sustained multiple organ ischaemia after transarterial chemoembolization with drug-eluting beads for hepatocellular carcinoma

Transarterial chemoembolization (TACE) with drug-eluting beads (DC beads) may enhance drug delivery to tumours and reduce systemic toxicity. TACE with DC beads leads to significantly fewer serious side-effects compared with conventional TACE. A 66-year-old man with hepatocellular carcinoma (HCC) complained of continuous abdominal pain 1 month after TACE with DC beads. At the time of TACE, angiography revealed severe stenosis of both hepatic arteries. The diagnostic work up on admission suggested severe bile duct injury with regional bile duct dilatation, segmental liver and spleen infarction, necrotizing pancreatitis, as well as gastric and duodenal ulcers. The pathology specimens of the duodenum contained DC beads that had passed through small vessels in the connective tissue. The patients condition appeared to improve after 2 weeks of antibiotic treatment and supportive care, but new multifocal liver and spleen infarction subsequently developed. After 2 months, he was well enough to be discharged. His HCC partially responded to the TACE with DC beads but eventually progressed and he died after 11 months. The present case report highlights unexpected ongoing multiple organ ischaemia in a 66-year-old man treated for HCC using TACE with DC beads. The use of TACE with DC beads should be carefully considered in patients with vascular strictures or aberrant blood supply.