Differential identification of urine crystals with morphologic characteristics and solubility test.

BACKGROUND: Urinary crystals are the most diverse forms of urine sediments. Reference images for typical urinary crystals are common, however, but images for interpreting atypical urinary crystals are very rare. The authors reviewed various forms and solubility tests of urine crystals to interpret atypical crystals found in clinical specimens. METHODS: We reviewed textbooks on urinary crystals and articles published in PubMed. Some atypical crystals were confirmed using a solubility test. RESULTS: The classification, shape, chemical structure, and solubility of the crystals were summarized. In the solubility test, some crystals showed different results; therefore, a new solubility test was proposed based on the literature review. We presented various types of calcium oxalates. CONCLUSIONS: These review articles will be helpful in the examination of atypical crystals found in clinical specimens. The solubility test requires additional studies to discriminate the inconsistent results between the authors.

Prognostic significance of glucose-related protein 94 in colorectal cancer.

AIMS: The expression of glucose-related protein 94 (GRP94), a member of the heat shock protein 90 family, was correlated with a variety of clinicopathological factors and patient survival in a large colorectal cancer (CRC) cohort. We aimed to elucidate the role of GRP94 in the prognosis of CRC patients. METHODS: Tissue microarray blocks were generated from 709 CRC samples and immunohistochemically stained for GRP94. RESULTS: Of the 709 tumours, 164 (23.1%) and 545 (76.9%) were classified in the low and high expression groups, respectively. GRP94 expression was high in CRC cases with larger tumours (p =  0.005) and advanced pT stage (p =  0.021). GRP94 expression was higher in females than males (p =  0.024). In univariate and multivariate survival analyses, high GRP94 expression was unexpectedly associated with better overall survival in CRC patients younger than 65 years of age (p =  0.001) CONCLUSION: Our conflicting results indicate that GRP94 has the ability to switch between oncogenic and tumour-suppressive roles depending on the conditions and microenvironment of the tumour cells. Furthermore, GRP94 could be a candidate biomarker to predict better prognosis in CRC patients.

Expression of miR-200c and its clinicopathological significance in patients with colorectal cancer.

MicroRNA-200c (miR-200c) is known to play a pivotal role in the regulation of epithelial-to-mesenchymal and mesenchymal-to-epithelial transition processes. However, the biological function of miR-200c in human carcinogenesis remains controversial. We examined the association of miR-200c expression with various clinicopathological factors, including KRAS mutation status and survival, in patients with colorectal cancer (CRC). The expression level of miR-200c was evaluated in 109 paired CRC and normal tissue samples using quantitative reverse transcription polymerase chain reaction. The KRAS mutation status of the CRC samples was determined using the PNAClamp™ KRAS Mutation Detection kit. Compared with the normal tissue group, miR-200c expression was significantly upregulated in the CRCs (P < .001). The expression of miR-200c was increased in CRCs with higher grade (P = .009), advanced stage (P = .042), and lymphovascular invasion (P = .003). Thirty-one CRCs (28.4%) had KRAS mutations in codon 12 or 13. CRCs with KRAS mutations had significantly higher miR-200c expression than CRCs with wild-type KRAS (P = .003). In survival analysis, high miR-200c expression was correlated with worse overall survival (P = .017) and recurrence-free survival (P = .048). Our results indicate that miR-200c is involved in tumor progression and aggressiveness in CRCs, and this oncogenic role of miR-200c may be triggered by activation of the KRAS signaling pathway.

Excessive Iodine Status among School-Age Children in Korea: A First Report.

BACKGROUND: Korea is considered an iodine sufficient country, and several studies have been conducted regarding iodine status in healthy Korean adults, pregnant women, and preschool children. However, data on iodine status in Korean school-age children are lacking. Therefore, the iodine nutrition status of Korean school-age children was investigated by measuring urine iodine concentration (UIC). METHODS: This cross-sectional study conducted between April and September 2016 comprised 373 school-age children. UIC was determined using a modified microplate method employing ammonium persulfate digestion followed by Sandell-Kolthoff reaction. RESULTS: The median UIC was 458.2 µg/L. Excessive iodine intake (>300 µg/L) was found in 286 children (76.7%), with extremely high values exceeding 1,000 µg/L in 19.6% of subjects. Insufficient iodine intake (<100 µg/L) was observed in eight children (2.1%). UIC values were not significantly different between sexes. CONCLUSION: Korean school-age children showed excessive iodine intake. Therefore, education regarding adequate iodine intake in school-age children is needed.

Isolation and Characterization of a Bacteriophage Preying an Antifungal Bacterium.

Several Bacillus species were isolated from rice field soils, and 16S rRNA gene sequence analysis showed that Bacillus cereus was the most abundant. A strain named BC1 showed antifungal activity against Rhizoctonia solani. Bacteriophages infecting strain BC1 were isolated from the same soil sample. The isolated phage PK16 had an icosahedral head of 100 ± 5 nm and tail of 200 ± 5 nm, indicating that it belonged to the family Myoviridae. Analysis of the complete linear dsDNA genome revealed a 158,127-bp genome with G + C content of 39.9% comprising 235 open reading frames as well as 19 tRNA genes (including 1 pseudogene). Blastp analysis showed that the proteins encoded by the PK16 genome had the closest hits to proteins of seven different bacteriophages. A neighbor-joining phylogenetic tree based on the major capsid protein showed a robust clustering of phage PK16 with phage JBP901 and BCP8-2 isolated from Korean fermented food.

Clinical significance of melanoma-associated antigen A1-6 expression in sputum of patients with squamous cell carcinoma of the larynx and hypopharynx.

BACKGROUND: Several studies have reported the expression of the melanoma-associated antigen (MAGE) gene in head and neck squamous cell carcinoma (HNSCC). In this study, we evaluated the correlations between MAGE expression in sputum and the clinical features and oncologic outcomes of SCC of the larynx and hypopharynx. METHODS: We performed a retrospective review of 119 patients treated for SCC of the larynx and hypopharynx and analysis of their induced sputum by nested reverse transcription-polymerase chain reaction (RT-PCR) to detect the MAGE-A1-6 gene. The associations between MAGE expression and clinical characteristics were analyzed. RESULTS: Expression of MAGE-A1-6 in sputum was identified in 57 of 119 patients (47.9%), and was independently correlated to double primary cancer (p = .024; odds ratio [OR] = 4.135). Expression of MAGE-A1-6 in sputum was correlated to poor survival. CONCLUSION: Expression of MAGE-A1-6 in sputum predicts poor oncologic outcome in patients with SCC of the larynx and hypopharynx. © 2015 Wiley Periodicals, Inc. Head Neck 38: E736-E740, 2016.

Phosphorylated 4E-binding protein 1 expression is associated with poor prognosis in small-cell lung cancer.

Phosphorylation of eukaryotic translation initiation factor 4E (eIF4E) binding protein (4E-BP1) results in release of eIF4E, which sequentially relieves translational repression and enhances oncogenic protein synthesis. We assessed the expression of phosphorylated 4E-BP1 (p-4E-BP1) in small-cell lung cancer (SCLC) and its correlation with clinicopathological factors and patient survival. This study included 117 SCLCs, which comprised 108 primary and 9 metastatic tumor tissues. We performed immunohistochemical staining for p-4E-BP1 in 117 tumors and found that 77 (66 %) were positive for p-4E-BP1 with cytoplasmic and/or nuclear immunostaining. The positive rate of p-4E-BP1 staining was significantly higher in never smokers (p = 0.034) and metastatic tumor tissues (p = 0.027). Patients with p-4E-BP1-positive SCLC tended to have poor performance status, although the difference was not statistically significant (p = 0.087). High p-4E-BP1 expression was significantly correlated with worse overall survival (OS) in all cohorts (p = 0.016). After stratification by clinical stage, p-4E-BP1 expression showed a stronger relationship with OS in patients with limited disease (p = 0.008). In addition, when stratified by treatment status, p-4E-BP1 expression was still significantly associated with worse OS in a subgroup of patients who completed treatment (p = 0.021). Our results indicate that p-4E-BP1 expression could represent oncogenic potential and contribute to the progression and aggressiveness of SCLC, suggesting it could be a candidate prognostic biomarker of SCLC, especially in limited disease.

Overexpression of phosphorylated 4E-binding protein 1 and its clinicopathological significances in gastric cancer.

Multiple intracellular transforming signals regulate eukaryotic translation initiation factor 4E (eIF4E)-binding protein (4E-BP1). The signals result in hierarchical phosphorylation of 4E-BP1, resulting in release of eIF4E, relieving translational repression and enhancing oncogenic protein synthesis. This study assessed the expression of phosphorylated 4E-BP1 (p-4E-BP1) in gastric cancer and its correlation with clinicopathological parameters and patient survival. Tissue microarray blocks were generated from 179 gastric carcinomas and immunohistochemically stained for p-4E-BP1. The expression of p-4E-BP1 was higher in tumors that were intestinal-type (P=0.028); had a diameter smaller than 5cm (P=0.001); were lower pathological T stage (P<0.001), N stage (P=0.004), or TNM stage (P<0.001); did not have distant metastasis (P=0.027). High p-4E-BP1 expression significantly correlated with prolonged overall survival (P=0.046) and disease-free survival (P=0.035), but was not an independent prognostic factor in multivariate analysis. Our results indicate that p-4E-BP1 is more highly expressed in early gastric cancers than in advanced ones, and has limited potential as an independent prognostic biomarker in patients with gastric cancer. Larger well-controlled studies with molecular validation are warranted to elucidate more exact prognostic significance and working mechanism of p-4E-BP1 in gastric cancer.

Expression of the brother of the regulator of imprinted sites gene in the sputum of patients with lung cancer.

BACKGROUND: Brother of the regulator of imprinted sites (BORIS) is a putative new oncogene that is classified as a cancer germline gene; however, its role in the development of cancer is unclear. This study investigated the expression of BORIS in lung cancer and its clinical implications. METHODS: The expression of BORIS messenger ribonucleic acid (mRNA) in the sputum of 100 patients with lung cancer (50 with squamous cell carcinoma, 36 with adenocarcinoma, and 14 with small-cell carcinoma) was evaluated by reverse transcription polymerase chain reaction. RESULTS: The overall expression rate of BORIS in patients with lung cancer was 36.0%: 19 of 50 squamous cell carcinomas (38.0%), 13 of 36 adenocarcinomas (36.1%), and 4 of 14 (28.6%) small-cell carcinomas. There was no significant difference in the BORIS expression according to age, gender, or histologic type. However, the mRNA expression of BORIS was significantly related to the pathologic cancer stage (p=0.004) and lymph node metastasis (p=0.001). The expression of the melanoma antigen gene family A1-6 was not associated with the expression of BORIS. CONCLUSION: Our results suggest that the expression of BORIS might be a negative prognostic factor in lung cancers and implicate BORIS as a molecular target for immunotherapy.

Expression of microRNA miR-126 and miR-200c is associated with prognosis in patients with non-small cell lung cancer.

MicroRNAs (miRNAs) are short non-coding RNAs that exert a critical influence on tumorigenesis through post-transcriptional modification and are considered to be potential biomarkers for the diagnosis or prognosis of various cancers. Although several miRNAs have been proposed as relevant biomarkers for non-small cell lung cancer (NSCLC), detailed working mechanisms and validated prognostic significance of these miRNAs remain controversial. In this study, we evaluated expression levels of miRNA-126 (miR-126) and miR-200c in 72 NSCLCs and 30 benign lung tissues by quantitative reverse transcription polymerase chain reaction (qRT-PCR) and analyzed the correlation of miRNA expression with a variety of clinicopathological factors and patient survival. Compared with the benign control group, miR-126 expression was significantly downregulated in NSCLCs (p < 0.001), while miR-200c expression was significantly upregulated in NSCLCs (p < 0.001). The expression of miR-126 was significantly higher in NSCLCs with a tumor size of ≤3 cm than in those with a tumor size of >3 cm (p = 0.026). There were no other significant associations between miRNA expression and clinicopathological features. In univariate survival analysis for all NSCLC patients, high miR-200c expression (p = 0.037), large tumor size (p = 0.026), and lymphovascular invasion (p = 0.012) were significantly correlated with worse overall survival. High miR-126 expression was significantly associated with favorable prognosis only in patients with adenocarcinoma (p = 0.033). In multivariate analysis, miR-200c and tumor size remained as independent prognostic factors. Our results suggest that miR-126 might play tumor-suppressive and miR-200c an oncogenic role, and these miR's are potential prognostic biomarkers for NSCLC.

Heat shock protein 70 (HSP70) expression is associated with poor prognosis in intestinal type gastric cancer.

Heat shock protein 70 (HSP70) is a molecular chaperone which plays an important role in cellular protection against various stressful stimuli and in the regulation of cellular growth and apoptosis. This study was conducted in gastric carcinoma (GC) to assess correlations of HSP70 expression with clinicopathological parameters and overall survival (OS). Tissue microarray blocks were constructed from 172 GCs and immunohistochemically stained for HSP70. Low HSP70 expression was found in 122 GCs (71 %), whereas 50 (29 %) had high expression. HSP70 expression was higher in tumours in the cardia (p = 0.008), with non-signet ring cell histology (p < 0.001), of intestinal type (p = 0.045) and of higher pathological T stage (p = 0.026). When considering the cohort as a whole, HSP70 expression did not correlate with OS (p = 0.092). In intestinal type carcinomas, however, high HSP70 expression significantly correlated with worse OS (p = 0.034). These results suggest that HSP70 expression might be an unfavourable prognostic factor in patients with GC, especially of intestinal type.

Expression of MAGE A1-6 and the clinical characteristics of papillary thyroid carcinoma.

BACKGROUND: The expression of melanoma-associated antigen (MAGE) gene has been studied in many types of cancer. In the present study we evaluated the correlation between MAGE expression and the clinical features and oncologic outcomes of patients with papillary thyroid cancer (PTC). MATERIALS AND METHODS: We performed a retrospective review of 85 patients who underwent surgery for PTC and analysis of their tumor tissue by nested reverse transcription-polymerase chain reaction (RT-PCR) with the MAGE common primer to detect the MAGE A1-6 gene. The associations between MAGE expression and clinical characteristics were analyzed. RESULTS: Expression of MAGE A1-6 in PTC was identified in 31 patients (36.5%). Only papillary thyroid microcarcinoma (PTMC) was significantly related to MAGE expression in our univariate analysis (p=0.002) and multivariate analysis (p=0.006). MAGE had no significant impact on survival. CONCLUSION: Expression of MAGE A1-6 in PTC is significantly correlated with the presence of PTMC. Our study suggests that MAGE expression may be related to early-stage PTC.

A Case of medullary thyroid carcinoma with de novo V804M RET germline mutation.

Many cases of RET proto-oncogene mutations of hereditary medullary thyroid carcinoma (MTC) have been reported in Korea. However, MTC with V804M RET proto-oncogene germline mutations have not been reported in Korea. A 33-yr-old man was diagnosed with a 0.7-cm sized thyroid nodule. Laboratory testing revealed serum calcitonin was elevated. The patient underwent total thyroidectomy with central compartment neck dissection for the thyroid tumor. RET gene analysis was performed in both the index patient and his family. There were no V804M RET mutation and abnormal laboratory findings within his family except the index patient. Therefore, this patient was a de novo V804M RET germline mutation.

Clinico-pathologic Parameters for Prediction of Microsatellite Instability in Colorectal Cancer.

PURPOSE: Although the incidence of microsatellite instability (MSI) accounts for 10-15% of cases of colorectal cancer, its clinical application for all colorectal cancers has widened. We attempted to identify clinical and pathological parameters that may be helpful in selection of patients with MSI-high (MSI-H). MATERIALS AND METHODS: A total of 120 resected colorectal cancers were enrolled retrospectively for this MSI study. Polymerase chain reaction (PCR) and denaturing high performance liquid chromatography and/or real time PCR methods with five markers and immunohistochemistry (IHC) for MLH1 and MSH2 were performed for analysis of cancer and blood specimens. Clinico-pathologic parameters, including IHC, were investigated in order to determine their usefulness as predictive factors of MSI. RESULTS: Among 120 cases of colorectal cancer, MSI was observed in 15 cases (12.5%), including 11 cases of MSI-H and four cases of MSI-low. Patients with MSI were younger, less than 50 years old, had a family history of cancer, Rt. sided colon cancer and/or synchronous multiple colorectal cancer, mucinous histologic type, and serum carcinoembryonic antigen group in the normal range. Results of multivariate analysis showed Bethesda guidelines, Rt. sided and/or synchronous multiple colorectal cancer, and negative expression of IHC for MLH1, which was consistently associated with MSI-H. MSI-H colorectal tumors have met at least one of these three parameters and their sensitivity and specificity were 100% and 72.5%, respectively. CONCLUSION: Bethesda guidelines, tumor location, and negative expression of MLH1 protein are important parameters for selection of patients with colorectal cancers for MSI testing. MSI testing is recommended for patients showing any of these three parameters.