Analysis of Expression Patterns of MicroRNAs That Are Closely Associated With Renal Carcinogenesis

Background: MicroRNAs (miRNA) are frequently dysregulated in clear cell renal cell carcinoma (ccRCC).Objective: This study aimed to elucidate the role of miRNA expression patterns in renal carcinogenesis and to identify the specific miRNAs that exhibit expression patterns closely associated with patient outcomes.Methods: We examined the expression patterns of selected miRNAs, including miRNA-155-5p, miRNA-122-5p, miRNA-21-5p, miRNA-185-5p, miRNA-106a-5p, miRNA-106b-3p, miRNA-34b-3p, miRNA-210-3p, miRNA-141-3p, miRNA-200c-3p, miRNA-135a-5p, miRNA-30a-5p, miRNA-218-5p, miRNA-429, miRNA-200a-3p and miRNA-200b-3p, in 96 samples of ccRCCs using the TaqMan real-time PCR method. In addition, cluster analysis was performed to stratify expression patterns of multiple miRNAs.Results: In the present study, three distinct subgroups could be clearly stratified in ccRCCs. Subgroup 1 was characterized by upregulation of miRNA-155-5p, miRNA-122-5p, miRNA-21-5p, miRNA-185-5p, miRNA-106a-5p, miRNA-106b-3p, miRNA-34b-3p and miRNA-210-3p. Subgroup 2 was closely associated with downregulation of miRNA-141-3p, miRNA200c-3p, miRNA-30a-5p, miRNA-218-5p, miRNA-429, miRNA-200a-3p and miRNA-200b-3p. Moreover, significant lower expression of miRNA-135a-5p was a distinctive feature of subgroup 3, which was correlated with metachronous metastasis. Among the individual markers in subgroup 3, miRNA-135a-5p was retained in multivariate analysis. The cutoff value of miRNA-135a-5p expression to identify the association of an altered level of miRNA-135a-5p with metachronous metastasis in ccRCCs was determined and showed excellent specificity.Conclusion: We suggest that the expression pattern of the chosen miRNAs is useful to identify renal carcinogenesis and to help identify the association of such expression patterns with metachronous metastasis in ccRCCs. In addition, miRNA-135a-5p was an excellent marker for prediction of metachronous metastasis

Classic Chromophobe Renal Cell Carcinoma Incur a Larger Number of Chromosomal Losses Than Seen in the Eosinophilic Subtype

Chromophobe renal cell carcinoma (chRCC) is a renal tumor subtype with a good prognosis, characterized by multiple chromosomal copy number variations (CNV). The World Health Organization (WHO) chRCC classification guidelines define a classic and an eosinophilic variant. Large cells with reticular cytoplasm and prominent cell membranes (pale cells) are characteristic for classic chRCC. Classic and eosinophilic variants were defined in 42 Swiss chRCCs, 119 Japanese chRCCs and in whole-slide digital images of 66 chRCCs from the Cancer Genome Atlas (TCGA) kidney chromophobe (KICH) dataset. 32 of 42 (76.2%) Swiss chRCCs, 90 of 119 (75.6%) Japanese chRCCs and 53 of 66 (80.3%) TCGA-KICH were classic chRCCs. There was no survival difference between eosinophilic and classic chRCC in all three cohorts. To identify a genotype/phenotype correlation, we performed a genome-wide CNV analysis using Affymetrix OncoScan$^{®}$ CNV Assay (Affymetrix/Thermo Fisher Scientific, Waltham, MA, USA) in 33 Swiss chRCCs. TCGA-KICH subtypes were compared with TCGA CNV data. In the combined Swiss and TCGA-KICH cohorts, losses of chromosome 1, 2, 6, 10, 13, and 17 were significantly more frequent in classic chRCC (p < 0.05, each), suggesting that classic chRCC are characterized by higher chromosomal instability. This molecular difference justifies the definition of two chRCC variants. Absence of pale cells could be used as main histological criterion to define the eosinophilic variant of chRCC

A Case of Cisternal Pilocytic Astrocytoma Diagnosed with the Balanced Steady-State Free Precession Sequence for Magnetic Resonance Imaging: A Rare Cause of Subarachnoid Hemorrhage

Objectives: In approximately 15% of cases of spontaneous subarachnoid hemorrhage (SAH), an obvious source of bleeding cannot be identified by angiography; these are considered cases of SAH of unknown etiology. A rare case of cisternal pilocytic astrocytoma (PA) presenting with SAH is reported. The usefulness of the balanced steady-state free precession (bSSFP) sequence for magnetic resonance imaging (MRI) to detect small cisternal lesions is discussed. Case Description: The case of a 73-year-old woman who developed repeated SAHs owing to a cisternal PA is presented. She experienced sudden onset of headache and vomiting, and brain computed tomography showed diffuse SAH, whereas angiography demonstrated normal vasculature. Follow-up imaging, including T1-weighted, T2-weighted, T1-weighted contrast-enhanced, and diffusion-weighted MRI, did not show any parenchymal or cisternal lesions, although computed tomography and fluid-attenuated inversion recovery MRI showed SAH in the same region. In contrast, the bSSFP sequence, taken as a different sequence on the same day, showed mixed-intensity reticular lesions in the left basal cistern, while neither hematoma nor positive findings were identified with the other sequences. Based on the radiologic finding and the repeated history of SAH, the lesions were partially removed 2 weeks after onset. Histological examination showed a PA. Conclusions: Despite being extremely rare, a small cisternal lesion should be considered as a cause of SAH of unknown etiology. The bSSFP sequence may be useful for detecting cisternal lesions that may be missed on the routine MRI sequences. Key words: Balanced steady-state free precession sequence, Cistern, Pilocytic astrocytoma, Subarachnoid hemorrhage, Unknown etiolog

Gastric crystal-storing histiocytosis without any underlying disorders: Report of a case

Crystal-storing histiocytosis (CSH) is a rare phenomenon in which crystalline material accumulates in the cytoplasm of histiocytes. Localized gastric CSH is an extremely rare condition. We report a case of localized gastric CSH in a 72-year-old female who presented with diffuse granular mucosa in the gastric fundus and body endoscopically. Biopsy specimens from the stomach showed accumulation of crystal-storing histiocytes, and the crystalline material was immunohistochemically positive for kappa light chains and polyclonal heavy chains. There were no crystal-storing histiocytes in other organs. For the past 5 years, the gastric CSH lesion has remained without any change, and no neoplastic or lymphoproliferative disease has developed. Once the diagnosis of CSH is established, it is necessary to check for an underlying lymphoplasmacytic disorder. However, some cases of localized gastric CSH are not associated with lymphoplasmacytic neoplasia, and these tend to have a good prognosis. Keywords: Crystal-storing histiocytosis, Stomach, Immunohistochemistry, Ultrastructur

Mesenteric extraovarian Sertoli-Leydig cell tumor without DICER1 hotspot mutation: a case report

Abstract Background Ovarian Sertoli-Leydig cell tumors (SLCTs) with androgenic manifestations harbor DICER1 mutations in 30–60% of cases. Ovarian SLCTs without DICER1 hotspot mutations have been reported to exhibit elderly onset and no androgenic manifestations. We present the first case of a primary mesenteric SLCT without DICER1 hotspot mutation. Case presentation An 84-year-old woman presented with a 75-mm mesenteric solid tumor. She presented no androgenic or estrogenic manifestations. She underwent ileocecal resection. Histologically, her mesenteric tumor showed histopathological features that resembled moderately differentiated SLCT. Moreover, DICER1 hotspot mutation was not detected. Conclusions We described the first case of heterotopic primary mesenteric SLCT without DICER1 hotspot mutation

Prognostic and predictive value of CD163 expression and the CD163/CD68 expression ratio for response to adjuvant chemotherapy in patients with surgically resected lung squamous cell carcinoma

Abstract Background Macrophages infiltrating the tumor microenvironment are defined as tumor‐associated macrophages (TAMs). TAMs can be polarized into different phenotypes, that is, proinflammatory M1 macrophages or anti‐inflammatory M2 macrophages. Particularly, M2 macrophages promote angiogenesis, wound healing, and tumor growth. This study aimed to evaluate whether M2 TAMs can serve as a useful marker to predict prognosis and benefit from adjuvant chemotherapy in patients with surgically resected lung squamous cell carcinomas (SCCs). Methods We examined 104 patients with SCC. Tissue microarrays were constructed, and the density of TAMs was analyzed by immunohistochemistry for expression of CD68 and CD163. The relationship between CD68 and CD163 expression and the CD163/CD68 expression rate and clinicopathological characteristics including patient outcomes were investigated. In addition, propensity score matching (PSM) analysis was conducted to test the hypothesis that these cells significantly influenced chemotherapy responses. Results Univariate analysis revealed that pathological stage, CD163 expression, and the CD163/CD68 expression ratio were significant prognostic factors. Multivariate analysis showed that these factors were all independent prognostic factors. Thirty‐four pairs were determined by using PSM analysis. Patients with a low CD163/CD68 expression ratio benefited more from adjuvant chemotherapy than those with a high ratio. Conclusion We suggest that M2 TAMs may be a useful marker to predict prognosis and differential benefit from adjuvant chemotherapy in patients with surgically resected lung SCCs

Classic chromophobe renal cell carcinoma incur a larger number of chromosomal losses than seen in the eosinophilic subtype

Chromophobe renal cell carcinoma (chRCC) is a renal tumor subtype with a good prognosis, characterized by multiple chromosomal copy number variations (CNV). The World Health Organization (WHO) chRCC classification guidelines define a classic and an eosinophilic variant. Large cells with reticular cytoplasm and prominent cell membranes (pale cells) are characteristic for classic chRCC. Classic and eosinophilic variants were defined in 42 Swiss chRCCs, 119 Japanese chRCCs and in whole-slide digital images of 66 chRCCs from the Cancer Genome Atlas (TCGA) kidney chromophobe (KICH) dataset. 32 of 42 (76.2%) Swiss chRCCs, 90 of 119 (75.6%) Japanese chRCCs and 53 of 66 (80.3%) TCGA-KICH were classic chRCCs. There was no survival difference between eosinophilic and classic chRCC in all three cohorts. To identify a genotype/phenotype correlation, we performed a genome-wide CNV analysis using Affymetrix OncoScan® CNV Assay (Affymetrix/Thermo Fisher Scientific, Waltham, MA, USA) in 33 Swiss chRCCs. TCGA-KICH subtypes were compared with TCGA CNV data. In the combined Swiss and TCGA-KICH cohorts, losses of chromosome 1, 2, 6, 10, 13, and 17 were significantly more frequent in classic chRCC (p < 0.05, each), suggesting that classic chRCC are characterized by higher chromosomal instability. This molecular difference justifies the definition of two chRCC variants. Absence of pale cells could be used as main histological criterion to define the eosinophilic variant of chRCC