EGFR, HER2, and MET gene amplification and protein expression profiles in biliary tract cancer and their prognostic significance.

BACKGROUND: There are limited conventional chemotherapy options for biliary tract cancers (BTCs), a heterogenous group of lethal, rare malignancies. The receptor tyrosine kinase (RTK) is closely associated with the progression of human malignancies through the regulation of cell cycle. Overexpression or amplification of RTKs has been investigated as a potential biomarker and therapeutic target in BTC; herein, we investigate the value of such interventions. MATERIALS AND METHODS: Overexpression of RTK proteins was examined by immunohistochemistry in 193 BTC samples, of which 137 were gallbladder carcinoma, 29 were perihilar cholangiocarcinoma, and 27 were intrahepatic cholangiocarcinoma. Silver in situ hybridization of MET and HER2 was performed to assess gene amplification. RESULTS: In the entire cancer group, gallbladder, perihilar, and intrahepatic, MET amplification rates were 15.7%, 19.0%, 3.4%, and 14.8%, respectively, and of HER2 amplification rates were 22.4%, 27.2%, 17.2%, and 3.7%, respectively. MET and HER2 protein expressions were significantly correlated with their gene amplification status. RTKs were significantly associated with adverse clinicopathologic features such as advanced pT category and lymph node metastasis. Overall survival was significantly shorter in MET-amplified (P = .024) and EGFR-overexpressed cases (P = .045). Recurrence-free survival was significantly correlated with HER2-amplified (P = .038) and EGFR-overexpressed cases (P = .046) in all patient groups. Overall and recurrence-free survival were significantly shorter in patients who were double positive for HER2 and EGFR. CONCLUSION: Our data suggested that MET, HER2, and EGFR might be potential therapeutic targets and that their co-expression is a strong prognostic factor for BTCs.

TXNIP Suppresses the Osteochondrogenic Switch of Vascular Smooth Muscle Cells in Atherosclerosis.

BACKGROUND: The osteochondrogenic switch of vascular smooth muscle cells (VSMCs) is a pivotal cellular process in atherosclerotic calcification. However, the exact molecular mechanism of the osteochondrogenic transition of VSMCs remains to be elucidated. Here, we explore the regulatory role of TXNIP (thioredoxin-interacting protein) in the phenotypical transitioning of VSMCs toward osteochondrogenic cells responsible for atherosclerotic calcification. METHODS: The atherosclerotic phenotypes of Txnip-/- mice were analyzed in combination with single-cell RNA-sequencing. The atherosclerotic phenotypes of Tagln-Cre; Txnipflox/flox mice (smooth muscle cell-specific Txnip ablation model), and the mice transplanted with the bone marrow of Txnip-/- mice were analyzed. Public single-cell RNA-sequencing dataset (GSE159677) was reanalyzed to define the gene expression of TXNIP in human calcified atherosclerotic plaques. The effect of TXNIP suppression on the osteochondrogenic phenotypic changes in primary aortic VSMCs was analyzed. RESULTS: Atherosclerotic lesions of Txnip-/- mice presented significantly increased calcification and deposition of collagen content. Subsequent single-cell RNA-sequencing analysis identified the modulated VSMC and osteochondrogenic clusters, which were VSMC-derived populations. The osteochondrogenic cluster was markedly expanded in Txnip-/- mice. The pathway analysis of the VSMC-derived cells revealed enrichment of bone- and cartilage-formation-related pathways and bone morphogenetic protein signaling in Txnip-/- mice. Reanalyzing public single-cell RNA-sequencing dataset revealed that TXNIP was downregulated in the modulated VSMC and osteochondrogenic clusters of human calcified atherosclerotic lesions. Tagln-Cre; Txnipflox/flox mice recapitulated the calcification and collagen-rich atherosclerotic phenotypes of Txnip-/- mice, whereas the hematopoietic deficiency of TXNIP did not affect the lesion phenotype. Suppression of TXNIP in cultured VSMCs accelerates osteodifferentiation and upregulates bone morphogenetic protein signaling. Treatment with the bone morphogenetic protein signaling inhibitor K02288 abrogated the effect of TXNIP suppression on osteodifferentiation. CONCLUSIONS: Our results suggest that TXNIP is a novel regulator of atherosclerotic calcification by suppressing bone morphogenetic protein signaling to inhibit the transition of VSMCs toward an osteochondrogenic phenotype.

Dermatofibroma-like dermal non-neural granular cell tumor.

Non-neural granular cell tumor (NNGCT) is a rare tumor with uncertain lineage. It presents as an asymptomatic polypoid or plaque-like lesion, especially on trunk. Because the granular cells are usually strongly reactive with S-100 stain, conventional granular cell tumors (GCTs) are regarded as those of neural or Schwann cell origin. Unlike GCTs, NNGCT is not reactive for S-100 protein and is thought to derive elsewhere, presumably from mesenchymal stem cells. A 20-year-old woman presented with a solitary, dermatofibroma-like, brownish nodule on her right arm. The lesion developed 3 months before presentation without subjective symptoms. Histopathologic examination revealed a grenz zone overlying a poorly circumscribed tumor extending through the reticular dermis. The tumor cells were large and polygonal, and they had numerous eosinophilic small granules in the cytoplasm. Immunohistochemical stains were positive for CD68, vimentin, factor XIIIa, CD10, and cyclin D1. Stains for S-100 protein, neuron-specific enolase, and CD34 were negative. Based on these findings, the lesion was diagnosed as dermal NNGCT.

Low expression of DUSP4 expression predicts unfavorable prognosis in gallbladder adenocarcinoma.

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.

EPHB2 expression is associated with intestinal phenotype of gastric cancer and indicates better prognosis by suppressing gastric cancer migration.

The protein tyrosine kinase Ephrin type-B receptor 2 (EPHB2) belongs to one of the intestinal stem cell signature genes and plays a crucial role in maintaining the crypt-villous axis. Herein, we aimed to investigate the expression of EPHB2 during gastric carcinogenesis and evaluated its prognostic and functional significance in gastric cancer (GC). EPHB2 expression was upregulated in intestinal metaplasia and GCs compared to normal antral and fundic glands. EPHB2 mRNA levels were strongly correlated with the intestinal stem cell markers OLFM4, LGR5, and EPHB3. Notably, EPHB2 expression was significantly correlated with CDX2 expression, and in vitro studies demonstrated that CDX2 expression increased both EPHB2 transcription and protein levels. In a large cohort of GC patients, EPHB2 positivity was observed in 39% of 704 GCs and was negatively correlated with tumor differentiation, lymphovascular invasion, and tumor-node-metastasis stages. Notably, EPHB2 positivity was associated with better overall survival, and it was an independent prognostic marker in intestinal-type GCs. Overexpression of EPHB2 in GC cell lines, MKN-28 and MKN-74, reduced migration activity by suppressing phosphorylation of focal adhesion kinase, whereas no significant difference was observed in proliferation rates. Thus, we suggest that EPHB2 acts as a tumor suppressor in GCs and can be a prognostic marker in intestinal-type GCs.

Loss of Single-Stranded DNA Binding Protein 2 Expression Is Associated with Aggressiveness and Poor Overall Survival in Patients with Invasive Breast Carcinoma.

BACKGROUND: Single-stranded DNA binding protein 2 (SSBP2) is involved in the DNA damage response and the maintenance of genome stability. Previous studies have suggested that SSBP2 has a tumor suppressor function or oncogenic function. Loss of SSBP2 expression has been reported in various tumors. However, the role of SSBP2 expression in invasive breast carcinoma has not been reported. METHODS: Immunohistochemical staining for SSBP2 was performed on tissue microarrays consisting of 491 invasive breast carcinoma cases. The result of nuclear SSBP2 staining was stratified as either negative or positive. Then, we investigated the correlations between SSBP2 expression and various clinicopathological parameters and patient outcomes. RESULTS: Loss of nuclear SSBP2 expression was observed in 61 cases (12.4%) of 491 invasive breast carcinomas. Loss of nuclear SSBP2 expression was significantly correlated with larger tumor size (p < 0.001, chi-squared test), higher histological grade (p = 0.016, Cochran-Armitage trend test), higher pathological T stage (p < 0.001, Cochran-Armitage trend test), estrogen receptor status (p < 0.001, chi-squared test), and molecular subtype (p < 0.001, chi-squared test). Kaplan-Meier survival analysis revealed that patients with loss of nuclear SSBP2 expression had worse overall survival (p = 0.013, log-rank test). However, loss of nuclear SSBP2 expression was not correlated with recurrence-free survival (p = 0.175, log-rank test). CONCLUSIONS: Loss of nuclear SSBP2 expression was associated with adverse clinicopathological characteristics and poor patient outcomes. SSBP2 acts as a tumor suppressor in invasive breast carcinoma and may be used as a prognostic biomarker.

Loss of DUSP4 Expression as a Prognostic Biomarker in Clear Cell Renal Cell Carcinoma.

Dual-specificity protein phosphatase 4 (DUSP4) is a negative regulator of mitogen-activated protein kinases. The prognostic impact of DUSP4 expression in renal cell carcinoma is not well studied. Therefore, we evaluated the clinicopathological implications of DUSP4 expression in clear cell renal cell carcinoma by performing immunohistochemistry (IHC). The clinical outcome according to DUSP4 expression was evaluated through survival analyses, and the association between mRNA expression and prognosis was confirmed by online analysis (Kaplan-Meier plotter). Loss of DUSP4 expression was noted in most histological subtypes of renal cell carcinoma. Loss of DUSP4 expression in clear cell renal cell carcinoma was significantly correlated with old age (p = 0.033), high histologic grade (p < 0.001), tumor necrosis (p < 0.001), and high pT category (p < 0.001). In survival analysis, loss of DUSP4 expression was associated with poor clinical outcomes in cancer-specific survival and recurrence-free survival (p = 0.010 and p = 0.007, respectively). Upon TCGA data analysis, patients with low DUSP4 mRNA expression showed a shorter overall survival (p = 0.023). These results suggest that loss of DUSP4 expression can be used as a potential biomarker for predicting clinical outcomes in clear cell renal cell carcinoma patients.

Low-Level Expression of MTUS1 Is Associated with Poor Survival in Patients with Lung Adenocarcinoma.

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.

Loss of YY1 expression predicts unfavorable prognosis in stage III colorectal cancer.

BACKGROUND: Yin Yang 1 (YY1), the multifunctional transcription factor, has recently been assigned biological properties related to human malignancies. YY1 can facilitate both tumor suppression and tumor growth. The conflicting role of YY1 in human malignancies is not yet fully explained. OBJECTIVE: In this study, we determined the clinicopathologic significance and prognostic role of YY1 in stage III colorectal cancer (CRC). MATERIALS AND METHODS: YY1 expression was evaluated immunohistochemically in tissue microarray from 345 CRCs. YY1 expression was scored by the proportion of tumor cells with nuclear staining into 4 scores (0, none; 1+, ≤10%; 2+, 10 to ≤25%; 3+, >25%). A score of 0 and 1 were considered as loss of expression. RESULTS: Loss of YY1 expression was observed in 49 (14.2%) out of 345 CRCs and was associated with larger tumor size (P = 0.004), tumor deposit (P = 0.008), and higher pathologic tumor (pT) stage (P = 0.004). In stage III group, loss of YY1 expression was associated with larger tumor size (P = 0.027) and tumor deposit (P = 0.011). Kaplan-Meier survival curves revealed no significant difference between patients with YY1 loss and patients with intact YY1 in both cancer-specific survival and recurrence-free survival (P = 0.330 and P = 0.470, respectively). In American Joint Committee on Cancer (AJCC) stage subgroup, loss of YY1 expression was associated with poor recurrence-free survival in AJCC stage III CRC (P = 0.038). CONCLUSION: Loss of YY1 expression was significantly associated with aggressive phenotypes and poor patient outcome in AJCC stage III CRC.

Correlation of CD47 Expression with Adverse Clinicopathologic Features and an Unfavorable Prognosis in Colorectal Adenocarcinoma.

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.

Transduodenal ampullectomy for ampullary tumor.

BACKGROUND: Transduodenal ampullectiomy (TDA) is a surgical local excision method that can be performed in patients with ampullary tumors, but it has not been widely used clinically. Recently, TDA is considered as a good alternative surgical technique in patients who are unable to perform the endoscopic ampullectomy (EA) or pancreaticoduodenectomy (PD) for various reasons. The purpose of this study is to evaluate the surgical outcomes of TDA and the clinicopathological significance of pathologic findings in TDA. METHODS: We reviewed the medical records of 31 patients diagnosed as ampullary tumor and underwent TDA from March 2004 to December 2019 in a single center. RESULTS: All 31 patients were planned to perform TDA, and 4 of them were converted to PPPD due to the marginal status results of frozen biopsy. Of the 31 patients, 19 were diagnosed with malignancy and 12 were diagnosed with benign. Of the 18 patients who were diagnosed as malignancy in final biopsy, only 9 patients (50%) were diagnosed with malignancy on the preoperative endoscopic biopsy. In 15 patients who underwent only TDA for malignancy, there was no recurrence during the follow-up period (mean: 51.1 months, range: 19-137). CONCLUSIONS: In benign ampullary tumor, TDA is a choice of treatment for patients who are unsuitable for endoscopic ampullectomy. TDA may be considered as an alternative operation in highly selective patients with early ampullary cancer (Tis and T1). Further studies on consensus of TDA indication for ampullary tumor will be needed in the future.

Low DUSP4 Expression Is Associated With Aggressive Phenotypes and Poor Prognosis in Gastric Cancer.

BACKGROUND/AIM: Dual-specificity protein phosphatase 4 (DUSP4) negatively regulates MAPK signaling and is involved in various cellular processes. We herein evaluated the relationship between DUSP4 expression and clinicopathological characteristics in a large series of gastric cancer samples. MATERIALS AND METHODS: DUSP4 expression was examined by immunohistochemistry in 508 gastric cancer samples. Cases were classified according to the TCGA molecular classification and HER2 amplification. Kaplan-Meier plots were used to predict the relationship between mRNA expression of DUSP4 and survival. RESULTS: Low expression of DUSP4 was significantly correlated with larger tumor size, higher pT category, positive nodal status, higher stage, lymphovascular invasion, perineural invasion, worse overall survival, and worse recurrence-free survival. No correlation was observed between DUSP4 expression and molecular characteristics. Bioinformatics analysis showed that low mRNA expression was associated with a poor prognosis. CONCLUSION: Low expression of DUSP4 is associated with aggressive phenotypes of gastric cancer and a poor prognosis.

Giant Infrascapular Rheumatoid Nodules Mimicking Elastofibroma Dorsi: A Case Report.

Rheumatoid nodules are the most common extra-articular presentations of rheumatoid arthritis. Although rheumatoid nodules can develop anywhere in the body, they develop most commonly in the subcutaneous region, where they are easily exposed to repetitive trauma or pressure. However, an infrascapular presentation has not yet been reported. We report a case of giant bilateral rheumatoid nodules that developed in the infrascapular area, complicating its distinction from elastofibroma dorsi on radiological examination.

Clinicopathological significance of CD47 expression in hepatocellular carcinoma.

AIMS: CD47 is upregulated on the surface of various tumour cells, and it is known to inhibit the phagocytosis of tumour cells by macrophages. Immunotherapy that targets CD47 has demonstrated success in preclinical trials and is now under clinical investigation for both solid and haematological malignancies. However, data regarding CD47 expression in hepatocellular carcinoma (HCC) tissue and its correlation with clinical outcomes in patients with HCC remain limited. Here, we investigated the clinicopathological features associated with CD47 expression in HCC. METHODS: CD47 expression was evaluated by immunohistochemistry in tissue microarray sections containing 166 HCC tissues. CD47 expression was considered positive if 10% or more tumour cells were stained. RESULTS: CD47 expression was observed in 36 (21.7%) of 166 HCC tissues and was significantly associated with frequent large vessel invasion, advanced American Joint Committee on Cancer stage and higher Ki-67 proliferation index. In the survival analyses, CD47 expression was not associated with recurrence-free survival or overall survival in total patients with HCC. However, in patients who received surgical resection without any adjuvant treatment, CD47 expression was associated with shorter recurrence-free survival. CONCLUSIONS: CD47 expression was significantly associated with adverse pathological features and poor clinical outcomes in patients with HCC who did not receive adjuvant treatment.

Nuclear Expression Loss of SSBP2 Is Associated with Poor Prognostic Factors in Colorectal Adenocarcinoma.

Single-stranded DNA binding protein 2 (SSBP2) is involved in DNA damage response and may induce growth arrest in cancer cells, having a potent tumor suppressor role. SSBP2 is ubiquitously expressed and the loss of its expression has been reported in various tumor types. However, the correlation between SSBP2 expression and colorectal cancer (CRC) prognosis remains unclear. SSBP2 nuclear expression was evaluated immunohistochemically in 48 normal colonic mucosae, 47 adenomas, 391 primary adenocarcinomas, and 131 metastatic carcinoma tissue samples. The clinicopathological factors, overall survival (OS), and recurrence-free survival were evaluated, and associations with the clinicopathological parameters were analyzed in 391 colorectal adenocarcinoma patients. A diffuse nuclear SSBP2 expression was detected in all normal colonic mucosa and adenoma samples. SSBP2 expression loss was observed in 131 (34.3%) primary adenocarcinoma and 100 (76.3%) metastatic carcinoma samples. SSBP2 expression was significantly associated with poor prognostic factors, such as vascular invasion (p = 0.005), high pT category (p = 0.045), and shorter OS (p = 0.038), using univariate survival analysis. Nuclear SSBP2 expression loss was significantly observed in colorectal carcinoma and metastatic carcinoma tissues, being associated with poor prognostic factors. SSBP2 acts as a tumor suppressor and may be used as a CRC prognostic biomarker.

The loss of nuclear expression of single-stranded DNA binding protein 2 of gastric adenocarcinoma and its prognostic role: Analysis of molecular subtype.

Single-stranded DNA binding protein 2 (SSBP2) is ubiquitously expressed, with several studies reporting it to be a tumor suppressor. We investigated SSBP2 expression and its clinicopathological significance in gastric cancer. SSBP2 expression was examined by immunohistochemistry in 539 gastric cancer sections. The cases were divided into three subtypes, namely, Epstein-Barr virus-associated (EBV), microsatellite unstable, and others (microsatellite stable and EBV negative), based on the molecular classification of The Cancer Genome Atlas (TCGA). Cases were also divided into two subgroups according to the amplification status of human epidermal growth factor receptor 2 (HER2). Most cases showed SSBP2 positivity, and only 24 (4.5%) cases displayed negative nuclear expression. Loss of nuclear expression correlated significantly with high pT category (P = 0.001), nodal metastasis (P = 0.002), and stage of progression (P = 0.005), with no correlation between molecular characteristics and SSBP2 expression. All HER2 amplification cases displayed positive SSBP2 expression. Negative SSBP2 cases showed significantly shorter recurrence-free survival (RFS) compared to positive SSBP2 cases (P = 0.008). Loss of nuclear expression of SSBP2 was significantly associated with shorter RFS in the microsatellite stable and EBV negative groups (P = 0.002), as well as the HER2 negative group (P = 0.007). However, there were no statistically significant differences in multivariate analyses. Loss of nuclear expression of SSBP2 was a poor prognostic factor, associated with stage of progression and recurrence, and showed no significant difference in molecular characteristics, including TCGA subtype and HER2 status.

Prognostic value of B-cell linker protein in colorectal cancer.

This study aimed to investigate the clinicopathological and prognostic impact of B-cell linker (BLNK) protein expression in colorectal cancer (CRC) as its function in CRC remains unexplored. We performed immunohistochemical staining for BLNK using tissue microarrays of 418 consecutive CRC samples; of these 10 were excluded due to inappropriate staining. The expression intensity and staining level was scored as 0-3 and 0-4, respectively, based on the percentage of positive cells. The immunoreactivity score (IRS) was calculated by multiplying these two scores. BLNK expression was observed in 222 patients (54.4 %). Lymph node metastasis (p = 0.031), right colon cancer (p = 0.026), mucinous adenocarcinoma (p < 0.001), and perineural invasion (p = 0.049) were more frequently observed in the IRS 4-12 group than in the IRS 0-3 group. At the same cutoff point, the 5-year recurrence-free survival rate of the patients with stage III was significantly lower than that observed in IRS 4-12 group (74.8 % ± 4.2 % vs. 54.2 % ± 8.5 %, p = 0.003). Multivariate analysis revealed IRS 4-12 to be an independent risk factor for recurrence (Hazard ratio 2.346, 95 % confidence interval 1.348-4.085, p = 0.003). In conclusion, overexpression of BLNK protein is an independent risk factor for CRC recurrence.

Low Expression of Single-stranded DNA Binding Protein 2 (SSBP2) Predicts Unfavourable Postoperative Outcomes in Patients With Clear Cell Renal Cell Carcinoma.

BACKGROUND: Single-stranded DNA binding protein 2 (SSBP2) is a subunit of a single-stranded DNA binding complex, which is involved in the maintenance of hematopoietic stem cells and stress responses. Numerous studies have suggested that SSBP2 functions as a tumor suppressor and is silenced through a pathway mediated by promoter hypermethylation. However, the role of SSBP2 in human renal cell carcinoma has not been reported, to date. Herein, we investigated the clinicopathological significance of SSBP2 expression in clear cell renal cell carcinoma (ccRCC). MATERIALS AND METHODS: We constructed tissue micro arrays consisting of 173 ccRCC tissues, and SSBP2 expression was evaluated semi-quantitatively based on the staining intensity and the proportion of stained cells. Regarding statistical analysis, the tissues were divided into two groups according to SSBP2 expression, and correlation of SSBP2 expression with various clinicopathological characteristics and patient outcomes was evaluated. RESULTS: Low SSBP2 expression was observed in 114 of 175 (65.9%) of ccRCC cases, and low SSBP2 expression was significantly correlated with larger tumor size (p=0.005, Chi-square test), higher WHO/ISUP histological grade (p<0.001, Chi-square test), tumor necrosis (p=0.008, Chi-square test), sarcomatoid change (p=0.021, Chi-square test), and higher pT AJCC stage (p=0.002, Chi-square test). Kaplan-Meier survival curves revealed that patients with low SSBP2 expression had worse recurrence-free survival (p=0.041, log-rank test). CONCLUSION: ccRCC with low SSBP2 expression was associated with adverse clinicopathological characteristics and poor patient outcomes.

Clinicopathologic features of rheumatoid nodules: a retrospective analysis.

OBJECTIVES: The clinical and histopathologic features of patients that have been diagnosed with rheumatoid nodules were investigated. METHODS: This study included patients with rheumatoid nodules, confirmed by histologic assessment, between 2005 and 2018 at the Hanyang University Hospital. Each patient had a total score of 6 or more according to the American College of Rheumatology criteria. RESULTS: A total of 57 cases were included in this study. The median age of the patients at the time of diagnosis was 57 years (range, 39-70 years). The average duration between the onset of treatment and occurrence of rheumatoid nodule was 11.6 years. Bone erosion was observed in 44 patients (77.2%). Among 57 patients, 56 (98.2%) were treated with disease-modifying anti-rheumatic drugs; most of the patients (87.7%) showed high-positive rheumatoid factor or high-positive anti-citrullinated protein antibodies. The foot, hand, and wrist, in order of decreasing frequencies, were the anatomical sites with the highest occurrence of rheumatoid nodules, whereas, the soft tissue adjacent to the joint, subcutis, dermis, lung parenchyma, and submucosal layer of the supraglottic area, also in an order of highest frequency, were the histological sites with the highest occurrence. Microscopically, central necrobiosis was present in all cases. Stromal fibrosis (96.5%), palisading of histiocytes (82.5%), perivascular lymphocytic infiltration (68.4%), and cleft or cystic degeneration (63.2%) were also observed. CONCLUSIONS: A clinicopathological review of cases diagnosed with rheumatoid nodules histologically was performed to confirm characteristics that can help clinicians understand the pathophysiology of the condition and make accurate diagnoses of rheumatoid nodules. Key Points • We reviewed the clinical, imaging, and histologic features of rheumatoid nodule. • The average duration between the onset of treatment and occurrence of rheumatoid nodule was 11.6 years. • Among 57 rheumatoid nodule patients, 98.2% were treated with disease-modifying anti-rheumatic drugs.