Bullous pemphigoid diagnosis: the role of routine formalin-fixed paraffin-embedded skin tissue immunochemistry.

The gold standard for diagnosing bullous pemphigoid (BP) is the detection of linear deposition of IgG and/or C3 at the dermoepidermal junction using direct immunofluorescence (DIF). Because DIF has several disadvantages, primarily the requirement for frozen specimens, we assessed the diagnostic value of immunohistochemical (IHC) staining for BP detection. Eighty-eight patients with bullous lesions were included in this study. IHC staining for C3d, C4d, and IgG was performed on 88 samples, which included specimens from patients with DIF-confirmed BP (n = 43), clinicopathologically suspected BP with negative DIF results (n = 9), and other bullous diseases (n = 36). Diagnosis based on positive results for C3d, C4d, or IgG in IHC staining detected 86% of DIF-confirmed BP cases. The sensitivity of IHC staining for the detection of DIF-confirmed BP cases and clinicopathologically suspected BP cases was similar to that of DIF (80.8% vs. 84.3%), but the specificity was higher (83.3% vs. 75.0%). Five of the nine clinicopathologically suspected BP cases were diagnosed using IHC staining. Thus, IHC staining of routine biopsy material could be an alternative method for diagnosing BP. IHC staining has considerable diagnostic potential, especially in cases with a high suspicion of BP, but negative or suboptimal DIF results.Please check and confirm the author names and initials are correct. Author 2: Given name: [Chul Hwan] Family name: [Kim], Author 3: Given name: [Yoo Jin] Family name: [Lee].Checked it.

BRCA1-associated protein 1 expression and prognostic role in prostate adenocarcinoma.

Purpose: As prostate cancer (PCa) is the second most commonly diagnosed cancer worldwide, finding novel markers for prognosis is crucial. BRCA1-associated protein 1 (BAP-1), a nuclear-localized deubiquitinating enzyme, has been reported in several human cancers. However, its prognostic role in PCa remains unknown. Herein, we assessed the prognostic and clinicopathologic significance of BAP-1 in PCa. Materials and Methods: Seventy surgical specimens from radical prostatectomy cases were examined. Two cores per case were selected for construction of tissue microarrays (TMAs). After the exclusion of two cases because of tissue sparsity, BAP-1 immunohistochemical expression was evaluated in 68 cases of formalin-fixed, paraffin-embedded TMA tissue blocks. The immunohistochemical stain was scored according to proportion of nuclear staining: negative (<10% of tumor cells) or positive (≥10% of tumor cells). Results: BAP-1 expression was negative in 30 cases (44.1%) and positive in 38 cases (55.9%). Positive BAP-1 expression was more common in pT3b disease than in pT2 (p=0.038). A high preoperative prostate-specific antigen level was correlated with BAP-1 expression (p=0.014). Age, lymphovascular invasion, perineural invasion, and grade group were not significantly correlated with BAP-1 expression. Patients with positive BAP-1 expression showed significantly shorter disease-free survival (p=0.013). Additionally, BAP-1 was an independent prognostic factor of PCa (p=0.035; hazard ratio, 9.277; 95% confidence interval, 1.165-73.892). Conclusions: Our study findings showed an association of BAP-1 expression with poor PCa prognosis and suggest a potential role for BAP-1 as a prognostic biomarker for PCa.

Morule-like features in pulmonary adenocarcinoma associated with epidermal growth factor receptor mutations: two case reports with targeted next-generation sequencing analysis.

Morules, or morule-like features, can be identified in benign and malignant lesions in various organs. Morular features are unusual in pulmonary adenocarcinoma cases with only 26 cases reported to date. Here, we describe two cases of pulmonary adenocarcinoma with morule-like features in Korean women. One patient had a non-mucinous-type adenocarcinoma in situ and the other had an acinarpredominant adenocarcinoma with a micropapillary component. Both patients showed multiple intra-alveolar, nodular, whorled proliferative foci composed of atypical spindle cells with eosinophilic cytoplasm. Targeted next-generation sequencing was performed on DNA extracted from formalin-fixed paraffin-embedded samples of the tumors. Results showed unusual epidermal growth factor receptor (EGFR) mutations, which are associated with drug resistance to EGFR tyrosine kinase inhibitors, revealing the importance of identifying morule-like features in pulmonary adenocarcinoma and the need for additional study, since there are few reported cases.

Long noncoding RNA HOTTIP overexpression: A potential prognostic biomarker in prostate cancer.

HOXA transcript at the distal tip (HOTTIP) is a long noncoding RNA (lncRNA), which is >200 nucleotides in length. HOTTIP expression has been demonstrated to play a crucial oncogenic role in cancer pathogenesis, and is said to be associated with poor human cancer prognosis. In prostate cancer, HOTTIP has been identified as an oncogene, but its clinicopathologic significance remains unclear. Array-based qRT-PCR was used to investigate lncRNA levels in 10 pairs of prostate cancer tissues and non-neoplastic parenchyma. Tissue microarray (TMA) was constructed using a total of 70 surgically resected prostatic adenocarcinoma tissues obtained from the Korea University Anam Hospital from 2009 to 2013. HOTTIP expression was determined by RNA in situ hybridization(ISH) and was correlated with clinicopathologic features. Increased HOTTIP expression was observed in all available prostate cancer tissue specimens compared with that in paired normal tissue. High HOTTIP expression was positively associated with bad clinicopathologic features, including higher pathologic T stage (p < 0.001), presence of extraprostatic extension (p < 0.001), seminal vesicle invasion (p < 0.001), perineural invasion (p < 0.001), and the tumor involvement of resection margin (p = 0.044). In particular, significantly increased HOTTIP expression was observed in specimens from patients in the high or very high-risk group, according to the 2018 National Comprehensive Cancer Network (NCCN) guidelines (p < 0.001). Also, patients with high HOTTIP expression showed poorer overall survival than those with low expression. In conclusion, we analytically validated the poor prognostic significance of HOTTIP overexpression and its association with bad clinicopathologic features, and present HOTTIP as a potential prognostic biomarker in prostate cancer.

A Case of Unexpected Clinostomum complanatum Infection Initially Presenting as Foreign Body in Pharynx.

A 46-year old man visited our outpatient clinic with complaint of foreign body sensation in throat after consuming raw freshwater fish 5 days ago. Laryngoscopic examination revealed a motile worm attached on posterior pharyngeal wall. The worm was removed using biopsy forceps under transnasal endoscopy and evidently identified as Clinostomum complanatum after microscopic examination. Patient's subjective foreign body sensation of throat and hyperemia of laryngeal mucosa remained for approximately 2 weeks post-removal, which were eventually resolved after administration of non-steroidal anti-inflammatory drug and anti-refluxant drug for 2 weeks. Treatment was ended at three weeks since the first visit. C. complanatum infections in humans are rare, and only four cases have been reported in Korea. Symptoms resembling pharyngitis or laryngitis occurs by consumption of raw, infected freshwater fish and treatment is done by mechanically removing the parasite.

High Yes-associated protein 1 with concomitant negative LATS1/2 expression is associated with poor prognosis of advanced gastric cancer.

The Hippo pathway is a tumour-suppressive pathway and its inactivation is known to be associated with progression and metastasis of various cancers. LATS1/2 (large tumour suppressor homolog 1 and 2), YAP1 (Yes-associated protein 1), and TEAD4 (TEA domain-containing sequence-specific transcription factors 4) are core components of the Hippo pathway, and their prognostic roles have not yet been studied in advanced gastric cancers (AGCs). A total of 318 surgically resected AGCs were retrieved. Immunolabelling for LATS1/2, YAP1 and TEAD4 was compared with clinicopathological factors including patients' survival. High expression of YAP1 and TEAD4 was identified in 108 (34.0%) and 131 (41.2%) cases, respectively, and 223 (70.1%) cases were negative for LATS1/2 expression. High YAP1 expression was significantly correlated with the presence of perineural invasion (p=0.032). High YAP1 and high TEAD4 expressions were significantly associated with poor overall survival (p<0.001 and p=0.003, respectively), and negative LATS1/2 expression was also associated with poor overall survival (p=0.002). Combined expression of YAP1highLATS1/2neg showed the worst overall survival (p<0.001). Expression of YAP1high (HR=2.938; 95% CI 1.726-4.998; p<0.001), LATS1/2neg (HR=0.371; 95% CI 0.181-0.758; p=0.007), and combined YAP1highLATS1/2neg (HR=13.785; 95% CI 3.245-58.554; p<0.001) were independent poor prognostic factors of AGC patients. Combined or individual expression of YAP1, LATS1/2, and TEAD4 can be used as prognostic markers of AGC patients.

Laser-Induced Dewetting of Metal Thin Films for Template-Free Plasmonic Color Printing.

Plasmonic color laser printing has several advantages over pigment-based technology, including the absence of ink and toner and the production of nonfading colors. However, the current printing method requires a template that should be prepared via nanofabrication processes, making it impractical for large-area color images. In this study, we show that laser-induced dewetting of metal thin films by a nanosecond pulsed laser can be effectively utilized for plasmonic color printing. Ag, Au, and their complex films deposited on a glass substrate were dewetted into different surface structures such as droplets, rods, and ripples, depending on the incident laser energy. The resulting morphological evolutions could be explained by Rayleigh and capillary instabilities. For a bimetallic film comprising Ag nanowires coated on a Au layer, a few different plasmonic colors were generated from a single sample simply by changing the laser fluence. This provides a possible method for implementing plasmonic color laser printing without using a prepatterned template.