Background/Objectives: Mutations in RAS/RAF are common in colorectal cancer (CRC) and play a pivotal role in guiding treatment selection. With the recent advent of immunotherapy, microsatellite (MSI) status, tumor mutation burden (TMB), and POLE mutations, particularly those leading to high TMB, have gained importance in CRC. This study aimed to examine the clinicopathological characteristics of patients with CRC with POLE mutations. Methods: We identified POLE mutations in patients with colorectal cancer who had available next-generation sequencing (NGS) results from a single institute in Korea. RAS/RAF status, MSI status, and TMB were evaluated, and based on the TMB results, patients with POLE mutations were classified as having either pathogenic or non-pathogenic mutations. After excluding non-Korean patients, we compared the groups based on the presence of pathogenic POLE mutations. Results: Five POLE mutations (A456P, P286R, R1111W, R609W, and V922I) were identified. Only A456P and P286R were associated with an exceptionally high TMB, resulting in two patients (1.1%) being categorized as having pathogenic POLE. The POLE-mutant group showed an extremely high TMB and tended to include younger patients. Among the two pathogenic cases, one showed poor histological differentiation, and the tumors were split between the right and left colons (one in each). Conclusions: CRC with POLE mutations tend to exhibit TMB-high, occur in younger patients, localize to the right colon, and display poor histological differentiation. Given that POLE mutations can serve as indicators for immunotherapy, recognizing these mutations is of clinical importance.
The efficacy of treating colorectal cancer (CRC) liver metastases is hindered by significant tumor heterogeneity, both within and between tumors. This diversity stems from varied cell populations and complex interactions in the tumor microenvironment, necessitating a deeper understanding of spatial organization and cellular communication patterns. We examined 23 formalin-fixed paraffin-embedded tissue samples from 11 patients, comprising primary lesions and matched liver metastasis (6 with synchronous and 5 with metachronous metastases) using NanoString 6K CosMx Spatial Molecular Imaging (SMI). Pathologists selected optimal fields of view at tumor invasive fronts. Image processing, cell segmentation, and feature extraction utilized an in-house CosMx SMI pipeline with the Cellpose algorithm. Following quality control, the remaining cells underwent unsupervised clustering with differential gene expression analysis and cell-to-cell interaction analyses performed using the Seurat R package. Analysis of 105, 624 high-quality cells revealed 23 distinct clusters, categorized as ten epithelial tumors, three cancer-associated fibroblast (CAF), two endothelial cells, five immune cells (T cell, Monocyte, Macrophage, SPP1+ Macrophage, and Plasma cell), alveolar cells, hepatocytes, and low complexity cell populations. We identified significant differences in gene expression between colon and liver CAFs, with liver CAFs displaying upregulation of 92 genes associated with epithelial-mesenchymal transition (EMT). Enhanced communication between CAFs, T cells, and macrophages was observed in liver metastases, with specific ligand-receptor pairs (SPP1-ITGA4/ITGB1, LGALS9-P4HB, LGALS9-CD44, CXCL12-CXCR4) enriched in the metastatic microenvironment. Our findings demonstrate distinct spatial heterogeneity and intercellular communication networks in CRC liver metastases. The identification of liver-specific CAF gene expression profiles and unique ligand-receptor interactions provides new insights into metastatic mechanisms and potential therapeutic targets. Jongwon Lee, Yeseul Kim, Hyo Seon Ryu, Jongmin Sim, Chungyeul Kim, Hyun Woo Kwon, Hyun Je Kim, Jong Min Park, Ah-Reum Lim, Jung Sun Kim, Hwa Jung Sung, Xingyi Guo, Jungmin Choi, Jungyoon Choi. Mechanisms of metastasis revealed through single-cell spatial transcriptome analysis in patients with liver metastatic colorectal cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 5289.
BACKGROUND/AIM:Appendiceal neuroendocrine tumors (ANETs) are the most prevalent type of appendiceal neoplasm and the fifth most common neuroendocrine tumor in the gastrointestinal tract. In this study, we described the clinicopathological features of patients with ANET. PATIENTS AND METHODS:We reviewed the clinicopathological findings and histopathological reports of six patients diagnosed with ANET between January 2014 and December 2023 at Korea University Medical Center, Anam Hospital. RESULTS:Six cases, comprising three males and three females, were diagnosed during procedures for lower abdominal pain or other medical reasons. Most tumors were less than 1 cm in size and located at the tip of the appendix. One patient had a large tumor (4.1 cm) with lymph node metastasis. Four tumors extended to the muscularis propria, whereas two infiltrated the subserosal soft tissue. The tumor cells exhibited a typical trabecular and nested pattern with monotonous round or oval nuclei. All patients had a mitotic count of less than 2 per 10 high-power fields and a Ki-67 labeling index of less than 1%, classifying them as having G1 well-differentiated tumors. Immunohistochemical staining showed that all cases were positive for CD56 and synaptophysin, and four were positive for chromogranin A. No recurrence or distant metastasis was observed during follow-up. CONCLUSION:ANETs are relatively uncommon and mostly benign in terms of prognosis. Because of their malignant potential, meticulous examination of appendectomy specimens is warranted to identify the presence of ANETs.
TROP2 overexpression was reported to predict poor prognosis and increased metastatic potential. This study evaluates TROP2 expression in brain metastases from diverse solid tumors and its consistency with primary tumors, addressing the limited research on TROP2 heterogeneity and its implications for CNS-targeted therapies. TROP2 immunohistochemical staining was performed on 61 brain metastatic tumors and 14 corresponding primary tumors. Based on TROP2 expression, cases were categorized into three groups: diffuse positive (> 95%), focal positive (0-95%), and negative (0%). Among the 61 brain metastatic tumors, TROP2 expression was diffusely positive in 62.3%, focally positive in 16.4%, and negative in 21.3%. Diffuse TROP2 positivity was most observed in tumors of lung origin, while focal positivity was predominant in colorectal metastases. In terms of pathologic diagnosis, adenocarcinoma was the most common type, with 55.6% showing diffuse positivity, 33.3% showing focal positivity, and 11.1% showing negativity. Notably, all cases of invasive breast carcinoma of no special type (IBC-NST) exhibited diffuse TROP2 positivity. No significant association was found between TROP2 expression levels and post-CNS metastasis survival. In the paired analysis of 14 cases with both primary and metastatic tumors, TROP2 expression was consistent between primary and metastatic sites in 78.6% of cases. However, 21.4% of cases, including colorectal adenocarcinoma and kidney clear cell carcinoma, showed discordant expression patterns between the primary and metastatic lesions. In conclusion, this study demonstrated variable TROP2 expression in brain metastasis samples and confirmed high consistency of TROP2 expression between primary and brain metastatic lesions.
Background/Aim: Vascular invasion (VI) in colorectal carcinoma (CRC) is an independent prognostic feature and a high-risk indicator for adjuvant chemotherapy in stage II CRC. This study evaluated the effect of elastic staining on VI detection. Patients and Methods: The VI was assessed using elastic staining in 154 patients with CRC. Based on hematoxylin and eosin (H&E) staining, cases were classified into three groups: absent (n=80), equivocal (n=23), and suspected (n=51). Two sections per case were evaluated for VI using elastic staining, and the presence of VI on one or both slides was confirmed. Finally, the correlation between the VI and other clinicopathological factors was analyzed. Results: The overall detection rate of VI using elastic staining was 67/154 (51.4%). VI was detected in 17/80 (21.3%), 3/23 (13.0 %), and 47/51 (92.2%) patients in the absent, equivocal, and suspected groups, respectively. VI was detected in both sections of the elastic staining slides in 28 cases, and in only one section in 38 cases. The VI was significantly associated with perineural invasion, M stage, and synchronous alone is not reliable, emphasizing the importance of elastic staining in improving VI detection. Therefore, we recommend the incorporation of elastic staining into routine pathological practice for all pT3 and pT4 CRC cases.
Abstract The nanoString GeoMx® Digital Spatial Profiling (DSP) enables the investigation of spatial assessment of tumors through high-plex profiling at the RNA and protein levels. Recent genomic analyses have revealed the intertumor heterogeneity between primary and metastatic lesions in colorectal cancer (CRC) patients. In CRC with liver metastases, current treatment strategies are mainly based on the parameters of primary tumors, and metastatic heterogeneity is a challenge since molecular heterogeneity contributes to therapeutic resistance. Furthermore, spatial intratumor heterogeneity exists within a single tumor between cancer cells (tumor) and their microenvironment (stroma) in human cancers. However, whether there are distinct spatial gene expression patterns of tumor and stroma between primary lesions and liver metastases remains unclear in CRCs. We examined 24 formalin-fixed paraffin-embedded tissue samples, including primary lesions and matched liver metastases from 12 patients (6 with synchronous and 6 with metachronous metastases) using NanoString GeoMx® DSP. The best regions of interest (ROI) with the invasive front boundary of the tumor were selected by pathologists. The ROI was segmented into PanCK-positive (tumor) and PanCK-negative (stroma), followed by a collection of indexed oligonucleotides and sequencing on Illumina instrument. Differential expression and pathways enrichment analyses were performed using R BioConductor package standR, limma, and GSEABase. Statistical significances were based on |Log2 fold change| > 1 and Benjamini-Hochberg-corrected P < 0.05. Immune cell abundance was estimated using the SpatialDecon package. In 12 metastatic patients (mean age, 61 years ± 7 [standard deviation]), liver metastatic stroma was associated with 68 upregulated and 93 downregulated genes compared to the primary stroma, with enrichment of 'Immune response' terms in gene set enrichment analysis (GSEA). A higher proportion of CD4 T memory cells and increased expression of cytotoxic genes (IL7R [2.02-fold], CD3E [1.75-fold], KLRB1 [1.68-fold], and GZMK [1.54-fold]) were observed in liver stroma compared to primary stroma. Conversely, liver metastatic tumors were associated only with 23 upregulated and 6 downregulated genes compared to primary tumors, with 'humoral response' terms enriched in GSEA. Similar patterns were observed in stratified analyses with synchronous and metachronous metastases, although a more prominent ‘immune response’ was observed in synchronous metastatic stroma compared to the primary stroma. We revealed that higher immune cell proportion and cytotoxic activity were observed in liver metastatic stroma compared to CRC stroma, providing novel insights into a unique etiology and may yield clinical implications for developing targeted treatment modalities for liver metastatic CRC patients. Citation Format: Jongwon Lee, Yeseul Kim, Hyo Seon Ryu, Jongmin Sim, Chungyeul Kim, Jong Min Park, Ah-Reum Lim, Jung Sun Kim, Hwa Jung Sung, Xingyi Guo, Jungmin Choi, Jungyoon Choi. Investigating spatial gene expression profiling in colorectal cancer: Tumor and stroma comparison between primary lesions and matched liver metastases [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 1160.
Gastric cancer is a significant public health concern, emphasizing the need for accurate evaluation of lymphatic invasion (LI) for determining prognosis and treatment options. However, this task is time-consuming, labor-intensive, and prone to intra- and interobserver variability. Furthermore, the scarcity of annotated data presents a challenge, particularly in the field of digital pathology. Therefore, there is a demand for an accurate and objective method to detect LI using a small dataset, benefiting pathologists. In this study, we trained convolutional neural networks to classify LI using a four-step training process: (1) weak model training, (2) identification of false positives, (3) hard negative mining in a weakly labeled dataset, and (4) strong model training. To overcome the lack of annotated datasets, we applied a hard negative mining approach in a weakly labeled dataset, which contained only final diagnostic information, resembling the typical data found in hospital databases, and improved classification performance. Ablation studies were performed to simulate the lack of datasets and severely unbalanced datasets, further confirming the effectiveness of our proposed approach. Notably, our results demonstrated that, despite the small number of annotated datasets, efficient training was achievable, with the potential to extend to other image classification approaches used in medicine.
BACKGROUND:Ossified cartilage is much more susceptible to cancer infiltration, but the reason remains unknown, and the relationship between the ossification pattern and cancer infiltration has not been studied.METHODS:The presence of thyroid cartilage ossification, cancer infiltration, ossification pattern (usual: direction from inferior to superior; unusual: other than the usual pattern), and distance between cancer and ossified cartilage were evaluated in laryngectomy specimens.RESULTS:There were 28 and 27 cases of usual and unusual patterns, respectively. There was no association between ossification pattern and cancer infiltration. However, the distance between the ossified area and cancer cells was greater in the usual pattern than in the unusual pattern (p = 0.006). And the usual pattern was more frequently observed in cases with a distance >1 mm than in cases with cancer infiltration or a distance ≤1 mm (p = 0.004).CONCLUSION:These results suggest the possibility of an active ossification due to tumor progression.
Background:Dual specificity phosphatase 4 (DUSP4), which regulates the mitogen activated protein kinases, has emerged as a tumor suppressor gene in several human malignancies. Aims and Objectives:In this study, we investigated the clinicopathologic significance and the prognostic role of DUSP4 in gallbladder adenocarcinoma. Materials and methods: DUSP4 expression was evaluated immunohistochemically in tissue microarray from 110 gallbladder adenocarcinoma samples and scored by H score system. The cut off (H score <170) was determined by ROC curve analysis. Results: Low expression of DUSP4 expression was observed in 57 (51.8%) out of 110 gallbladder adenocarcinoma samples. Low expression of DUSP4 expression was significantly associated with high histologic grade (P = 0.017), high pT stage (P = 0.002) and high AJCC stage (P = 0.007). Kaplan Meier survival curves revealed that patients with low expression of DUSP4 expression had significantly worse cancer specific survival (P = 0.024, log rank test). However, there was no significant association between DUSP4 expression and recurrence free survival. Conclusions:In conclusion, gallbladder adenocarcinoma with low expression of DUSP4 expression was associated with adverse clinicopathologic characteristics and poor patient outcome.patient outcome.
Purpose:Although adjuvant chemotherapy (CTx) is still recommended for high-risk patients with hormone receptor-positive and human epidermal receptor (HER)-2-negative breast cancer, recent studies found that selected patients with low disease burden may be spared from CTx and receive hormonal treatment (HT) alone. This study aims to evaluate the trends of treatment (CTx + HT vs. HT alone) in Korea and to assess the impact on overall survival (OS) according to treatment pattern.Methods:The Korean Breast Cancer Society Registry was queried (2000 to 2018) for women with pT1-2N0-1 hormone receptor-positive and HER2-negative disease who underwent surgery and adjuvant systemic treatment (CTx and HT). Clinicopathologic factors, change in pattern of treatment over time, and OS for each treatment option were analyzed.Results:A total of 40,938 women were included in the study; 20,880 (51.0%) received CTx + HT, while 20,058 (49.0%) received HT only. In recent years, there has been a steady increase in the use of HT alone, from 21.0% (2000) to 64.6% (2018). In Cox regression analysis, age, type of breast and axillary operations, T and N stages, body mass index, histologic grade, and presence of lymphovascular invasion were prognostic indicators for OS. There was no significant difference between CTx + HT and HT alone in terms of OS (P = 0.126).Conclusion:Over the years, there has been a shift from CTx + HT to HT alone without a significant difference in OS. Therefore, HT alone could be a safe treatment option in selected patients, even those with T2N1 disease.
Cell adhesion molecule 4 (CADM4) is a novel tumor suppressor candidate. The prognostic implications of CADM4 in gastric cancer have not been conclusively elucidated. Therefore, we evaluated the clinicopathological significance and prognostic value of CADM4 expression in a large series of patients with gastric adenocarcinoma. Immunohistochemical staining for CADM4 was performed on 534 gastric adenocarcinomas. We evaluated the associations between CADM4 expression and the clinicopathological and molecular characteristics of the adenocarcinomas. The prognostic effect of CADM4 expression was evaluated by survival analyses. Low CADM4 expression was significantly associated with young age (p = 0.046), aggressive histological type (p < 0.001), high pT category (p < 0.001), nodal metastasis (p < 0.001), high stage (p = 0.002), lymphovascular invasion (p = 0.001), and perineural invasion (p = 0.001). Low CADM4 expression was more frequently observed in tumors without human epidermal growth factor receptor 2 (HER2) amplification (p = 0.002). Low CADM4 expression was associated with worse overall survival (p = 0.007) and recurrence-free survival (p = 0.005) in the survival analyses. Low CADM4 expression was associated with aggressive clinicopathological features and poor clinical outcomes. CADM4 can act as a tumor suppressor in gastric adenocarcinoma and can be considered a prognostic biomarker.
Background: The expression of ArfGAP with SH3 domain ankyrin repeat and PH domain 1 (ASAP1) is increased in various types of cancer, showing potential as a prognostic marker. The clinicopathological implications of ASAP1 expression in patients with hepatocellular carcinoma (HCC) remain unclear. We thus investigated the clinicopathological significance and prognostic effect of ASAP1 expression in HCC patients. Materials and Methods: ASAP1 expression was assessed in 149 HCC tissue samples using immunohistochemistry (IHC). The associations between ASAP1 expression and clinicopathological characteristics were analyzed. The prognostic effect of ASAP1 expression in patients with HCC was evaluated based on survival analyses and confirmed using a web-based tool. Results: ASAP1 expression was observed in the cytoplasm of tumor cells. High ASAP1 expression was observed in 89 (59.7%) of 149 cases. High ASAP1 expression was significantly associated with male patients (p = 0.018), higher histological grade (p = 0.013), vessel invasion (p = 0.021), and higher stage (p = 0.020). High ASAP1 expression was associated with shorter overall survival (OS; p = 0.041) and recurrence-free survival (RFS; p = 0.008) based on Kaplan-Meier survival analyses. Web-based analysis using Kaplan-Meier (KM) plotter showed high mRNA ASAP1 expression to be associated with short OS (p = 0.001). Conclusion: High ASAP1 expression was associated with aggressive clinicopathological characteristics and poor clinical outcomes in patients with HCC. ASAP1 can be considered a prognostic biomarker in HCC patients.
The role of CD47 expression as a ‘do not eat me’ signal that inhibits phagocytosis of tumor cells by macrophages is well established. Immune checkpoint therapy that targets CD47 has been successful in preclinical trials and is currently undergoing clinical investigation for various human malignancies. Here, the clinicopathological correlation with CD47 expression in clear cell renal cell carcinoma (ccRCC) was explored. CD47 expression was evaluated by immunohistochemical staining in tissue microarray sections of 235 ccRCC tissues. CD47 expression was observed in 28 (11.9%) of 235 ccRCC tissues and was significantly associated with higher WHO/ISUP grade (p = 0.001), frequent lymphovascular invasion (p = 0.036), frequent renal vein thrombus (p = 0.018), frequent sinus fat invasion (p = 0.004), frequent sarcomatous change (p = 0.001), higher pT stage (p = 0.002), higher pN stage (p = 0.002), higher pM stage (p < 0.001), and advanced American Joint Committee on Cancer stage (p = 0.002). In the survival analyses, positive CD47 expression was associated with cancer-specific survival (p = 0.003). However, positive CD47 expression was not associated with recurrence-free survival. In conclusion, CD47 expression was associated with adverse clinicopathological parameters and cancer-specific survival in patients with ccRCC.
Microtubule-associated tumor suppressor 1 (MTUS1) is thought to be downregulated in arious human cancers, which suggests its role as a tumor suppressor. This study investigated the clinicopathological significance of MTUS1 expression in lung adenocarcinoma. Tissue microarray blocks consisting of 161 cases were constructed, and immunohistochemical staining was used to assess MTUS1 expression. Correlations of MTUS1 expression and clinicopathological parameters were analyzed. In addition, we used public databases and performed bioinformatics analysis. Low level of MTUS1 was significantly associated with higher clinical stage (p = 0.006), higher tumor stage (p = 0.044), lymph node metastasis (p = 0.01), worse histologic grade (p = 0.007), lymphovascular invasion (p = 0.014), and higher Ki-67 proliferation index (p < 0.001). Patients with low MTUS1 expression also showed shorter disease-free survival (p = 0.002) and cancer-specific survival (p = 0.006). Analysis of data from the Cancer Genome Atlas confirmed that the mRNA expression of MTUS1 in lung adenocarcinoma was significantly lower than that of normal lung tissue (p = 0.02), and patients with decreased MTUS1 expression showed significantly shorter overall survival (p = 0.008). These results suggest that MTUS1 may be a potential biomarker for predicting clinical outcomes in lung adenocarcinoma patients.
CD47, a transmembrane protein, is widely overexpressed on the tumor cell surface. However, the prognostic significance of CD47 expression in colorectal adenocarcinoma (CRA) has not yet been clarified. Here, we investigated the clinicopathologic significance of CD47 expression in CRA. CD47 expression was evaluated via immunohistochemical analysis of microarray sections of 328 CRA tissues. CD47 expression was observed in 53 (16.2%) of the 328 CRA tissues, and positive expression was associated with lymphatic invasion (p = 0.018), perineural invasion (p = 0.024), tumor budding (p = 0.009), the pathologic N stage (p = 0.022), and the American Joint Committee on Cancer (AJCC) stage (p = 0.027). In survival analyses of 329 patients, a positive CD47 expression was associated with a poor recurrence-free survival (RFS) (p = 0.032). In multivariate analysis, however, it was not an independent prognostic factor. In patients who underwent surgical resection without adjuvant treatment, a positive CD47 expression was associated with a shorter RFS (p = 0.001) but not with cancer-specific survival (CSS). In patients who received postoperative adjuvant treatment, no significant differences were found in both RFS and CSS. In conclusion, we investigated CD47 expression in 328 CRA tissues. A positive CD47 expression was observed in a minority (16.2%) of the tissues and was significantly associated with adverse clinicopathologic features and a poor patient outcome.
In the era of precision medicine, accurate and reproducible assignment of cell-of-origin (COO) in diffuse large B-cell lymphoma patients has become important. The Lymph2Cx assay is accurately determining COO by analyzing RNA expression of 20 selected genes while the Hans algorithm based on immunohistochemistry is the most popular method for routine daily diagnosis. However, there are discrepancies between the 2 methods, which need to be evaluated for better correlation. We prospectively analyzed 156 cases of diffuse large B-cell lymphoma, not otherwise specified to analyze the characteristics of discrepancy groups of COO determined by Lymph2Cx and Hans algorithm. We investigated the pattern and cause of discrepancy of COO assigned by the 2 methods. Hans algorithm classified 50 cases (32%) as germinal-center B-cell-like (GCB) type and 106 cases (68%) as non-GCB type. Lymph2Cx assay assigned 43 cases (28%) as GCB type, 94 cases (60%) as activated B-cell-like type, and 19 cases (12%) as intermediate/unclassified type. The agreement rate was 86% after exclusion of unclassified type. With regard to the clinicopathologic factors related with discrepancy between Hans algorithm and Lymph2Cx assay, endoscopic biopsy of the gastrointestinal tract (4/11, 36%) showed higher discrepancy rate (P=0.052). Immunophenotypically, CD10/BCL6/MUM1 GCB type and CD10/BCL6//MUM1 (=30%, low level expression) non-GCB type exhibited a significantly higher discrepancy rate (6/13, 46%; 4/13, 31%) (P=0.0001). Activated B-cell-like subgroup via Lymph2Cx assay predicted poor progression-free survival (mean survival duration 28.6 mo, P=0.049) compared with the GCB and unclassified type. Hans algorithm revealed no significant difference in progression-free survival and overall survival (P=0.122 and 0.121). These results suggest that when assigning COO via Hans algorithm, CD10/BCL6/MUM1 GCB type and CD10/BCL6/MUM1 (=30%, low level) non-GCB type require careful interpretation, especially if the MUM1 staining is weak and heterogeneous in the biopsied specimen.
Background/Aim: Microtubule-associated scaffold protein 1 (MTUS1) acts as tumor suppressor in several cancer types. This study assessed the relationship between clinicopathological characteristics and expression of microRNA candidates based on MTUS1 expression in gallbladder cancer (GBC). Materials and Methods: MTUS1 expression was evaluated by immunohistochemical staining of tissue microarrays from 109 cases of GBC. The association of MTUS1 expression with clinicopathological factors was explored. Two microRNA candidates (miR-19a-3p, and miR-19b-3p), which were identified by a literature review and computational analysis, were assessed in GBC tissue samples by quantitative real-time polymerase chain reaction. Results: Low MTUS1 expression in GBC was associated with high histological grade, perineural invasion, lymphovascular invasion, high T-stage, advanced TNM stage, poorer disease free survival, and poorer cancer-specific survival. No statistical association between MTUS1 expression and expression of microRNA candidates was observed. Conclusion: MTUS1 may act as tumor suppressor and might be a potential biomarker for predicting prognosis in GBC.
BACKGROUND/AIM:Microtubule-associated tumor suppressor 1 (MTUS1) is a novel tumor suppressor involved in proliferation and migration, and down-regulation of MTUS1 is associated with the poor prognosis of several cancers. We evaluated the clinicopathological significance of MTUS1 expression in renal cell carcinoma (RCC).PATIENTS AND METHODS:We assessed MTUS1 expression by immunohistochemical staining of tissue microarrays from 249 cases of RCC. We analyzed the correlation of MTUS1 expression and clinicopathological characteristics. Additionally, we used public databases and performed bioinformatics analysis.RESULTS:We investigated The Cancer Genome Atlas databases and identified that MTUS1 mRNA expression was significantly lower in RCC tissues than in normal tissues. Loss of MTUS1 expression was correlated with high WHO/ISUP nuclear grade, lymphovascular invasion, renal vein thrombus, and high pT stage in patients with RCC. Although there was no statistically significant correlation between MTUS1 expression and patients' prognosis in our cohort, MTUS1 overexpression was significantly correlated with a favorable prognosis in public data.CONCLUSION:Loss of MTUS1 expression in RCC might be a potential biomarker for predicting clinical outcome.
The purpose of this study was to evaluate changes in the proportion of lymphoid neoplasm subtypes in South Korea. A total of 8615 cases of lymphoid neoplasms diagnosed in 1997-2016 at Samsung Medical Center in South Korea were classified according to the 2008 World Health Organization system. The total number and proportion of lymphoid neoplasms were compared between these two decades, with data from nationwide studies, and with other countries. To evaluate changes in the proportion of subtypes, crude rate of each subtype per 100 lymphoma patients during each decade and age adjusted rate were calculated. There were 3024 patients with lymphoid neoplasm in 1997-2006, and 5591 in 2007-2016, which represents an average increase of 1.85 times over the 20-year study period. Crude rate and age adjusted rate were increased in Hodgkin's lymphoma and mature B cell lymphoma while precursor lymphoid neoplasms and mature T cell lymphoma were decreased. Among B cell neoplasms, age adjusted rate of plasma cell neoplasm, follicular lymphoma, mantle cell lymphoma increased while there was no significant change in extranodal marginal zone lymphoma and Burkitt lymphoma. The increase in follicular lymphoma was due to the increases in nodal follicular lymphoma of low grade and duodenal-type follicular lymphoma. These results are consistent with the dynamics of causative factors, including socioeconomic factors, in Korea.