The Correlations between the Intensity of Histopathological Ubiquitin-Specific Protease 11 Staining and Progression of Prostate Cancer.

BACKGROUND: Ubiquitin-specific protease 11 (USP11), one of the principal phosphatase and tensin homolog (PTEN) deubiquitinases, can reserve PTEN polyubiquitination to maintain PTEN protein integrity and inhibit PI3K/AKT pathway activation. The aim of the current study was to investigate the associations between immunohistochemical USP11 staining intensities and prognostic indicators in individuals with prostate cancer. METHODS: Tissue microarrays (TMAs) were performed for human prostate cancer and normal tissue (control) samples. Data on patient's age, Gleason score, plasma prostate-specific antigen (PSA) titer, disease stage, and presence of seminal vesicles, lymph nodes, and surgical margin involvement were collected. A pathologist who was blinded to the clinical outcome data scored the TMA for USP11 staining intensity as either positive or negative. RESULTS: Cancerous tissues exhibited lower USP11 staining intensity, whereas the neighboring benign peri-tumoral tissues showed higher USP11 staining intensity. The degree of USP11 staining intensity was lower in patients with a higher PSA titer, higher Gleason score, or more advanced disease stage. Patients who showed positive USP11 staining were more likely to have more optimal clinical and biochemical recurrence-free survival statistics. CONCLUSIONS: USP11 staining intensity in patients with prostate cancer is negatively associated with several prognostic factors such as an elevated PSA titer and a high Gleason score. It also reflects both biochemical and clinical recurrence-free survival in such patients. Thus, USP11 staining is a valuable prognostic factor in patients with prostate cancer.

Label-free histological analysis of retrieved thrombi in acute ischemic stroke using optical diffraction tomography and deep learning.

For patients with acute ischemic stroke, histological quantification of thrombus composition provides evidence for determining appropriate treatment. However, the traditional manual segmentation of stained thrombi is laborious and inconsistent. In this study, we propose a label-free method that combines optical diffraction tomography (ODT) and deep learning (DL) to automate the histological quantification process. The DL model classifies ODT image patches with 95% accuracy, and the collective prediction generates a whole-slide map of red blood cells and fibrin. The resulting whole-slide composition displays an average error of 1.1% and does not experience staining variability, facilitating faster analysis with reduced labor. The present approach will enable rapid and quantitative evaluation of blood clot composition, expediting the preclinical research and diagnosis of cardiovascular diseases.

Focal Segmental Glomerulosclerosis Followed by Acute Hepatitis A Infection: Case Report.

Background and Objectives: Chronic viral hepatitis such as hepatitis B or hepatitis C is frequently related to nephropathies, yet acute hepatitis A virus (HAV) infection is an exception. Materials and Methods: A 43-year-old male presented with jaundice accompanied by nausea and vomiting. The patient was diagnosed with acute HAV infection. Although the liver function improved after conservative treatment, various symptoms such as proteinuria, hypoalbuminemia, generalized edema and pleural effusion persisted. Due to nephrotic syndrome, the patient was referred to the clinic of the nephrology department and a renal biopsy was performed. Results: The result of the renal biopsy was focal segmental glomerulosclerosis (FSGS) based on histology, electron microscopy and immunohistochemistry. Therefore, based on the clinical history and biopsy results, the patient was diagnosed as having FSGS aggravated by acute HAV infection. Proteinuria, hypoalbuminemia and generalized edema were improved after prednisolone treatment. Conclusions: Although less common, acute HAV infection can also present with an extrahepatic manifestation, for example, FSGS. Hence, clinical attention is required if proteinuria or hypoalbuminemia persists in patients with acute HAV infection.

The correlation between the expression of ubiquitin-conjugating enzyme 2C and prostate cancer prognosis.

PURPOSE: Ubiquitin-conjugating enzyme E2 C (UBE2C) is known to show a causal relationship with cancer development and advancement. The role of UBE2C is to control the mitotic spindle checkpoint. Excess UBE2C has been identified in patients with advanced prostate cancer. The objective of the present study was to examine positive connections between the expression of UBE2C and prognostic factors for prostate cancer. METHODS: Prostate cancer patients' clinical data were analysed. Tissue microarrays (TMAs) were also performed for human prostate cancer tissues (n = 335) and adjacent non-neoplastic tissues (n = 22). TMA slides were incubated with antibodies against UBE2C. Cores were scored by a pathologist who was blind to cancer results. RESULTS: Of 335 prostate cancer patients, 200 could be assessed for biochemical recurrence, clinical recurrence, and overall survival. Human prostate cancer tissues showed higher expression of UBE2C than adjacent non-neoplastic tissues. High expression level of UBE2C showed a strong positive relationship with a high prostate-specific antigen (PSA), Gleason's score, and pathological stage of prostate cancer. Patients with a higher UBE2C grade demonstrated greater lymphatic engagement of prostate cancer than those with a lower UBE2C grade. CONCLUSION: The expression of UBE2C has positive correlations with several prognostic factors for prostate cancer. Thus, investigating the expression level of UBE2C staining is a promising tool for predicting prostate cancer prognosis.

Rare case of hepatocellular carcinoma metastasis to urinary bladder: A case report.

BACKGROUND: Hepatocellular carcinoma (HCC) is a primary liver cancer with high prevalence and mortality. There are many cases of advanced HCC at the time of diagnosis. Treatment methods and prognosis are different depends on whether metastasis is present. Thus, it is necessary to make an accurate evaluation at the time of diagnosis. Extrahepatic metastases of HCC usually occur through hematogenous spread or through adjacent organs such as the peritoneum. Metastasis to the urinary bladder alone is rare. Here, we report a rare case of biopsy-proven solitary metastasis of HCC to the bladder in a 60-year-old woman. CASE SUMMARY: A 60-year-old female patient was found to be positive for hepatitis B surface antigen by chance after abdominal ultrasonography showed abnormal findings. Thus, liver dynamic computed tomography (CT) was performed. The patient visited the hospital for further examination. Ultrasound and CT showed 3.6 cm sized arterial enhancing mass in segment 5 and an infiltrative mass in segment 8. The patient was diagnosed with HCC through liver dynamic magnetic resonance imaging and liver biopsy. Afterwards, she underwent two transcatheter arterial chemoembolizations within five months for HCC. During follow-up, a newly appeared bladder tumor was found on liver dynamic CT. She underwent transurethral resection of the bladder tumor for diagnosis and treatment. The tissue was confirmed as metastatic HCC. CONCLUSION: Although rare, metastasis to urinary bladder from HCC can occur without evidence of other distant metastases. Thus, regular follow-up imaging examination and clinical attention are required.

Minimal Change Disease Is Associated with Mitochondrial Injury and STING Pathway Activation.

We hypothesized that minimal change disease (MCD) pathogenesis may be associated with mitochondrial injury, and that the degree of mitochondrial injury at the time of diagnosis may serve as a valuable prognostic marker. We compared urinary mitochondrial DNA (mtDNA) at the time of diagnosis in patients with MCD and age- and sex-matched healthy controls (MHC) (n = 10 each). We analyzed the site and signal intensity of immunohistochemical (IHC) staining of stimulator of interferon genes (STING) using kidney tissues at the time of diagnosis in patients with MCD. Patients with MCD were divided into high (n = 6) and low-intensity (n = 14) subgroups according to the signal intensity. Urinary mtDNA levels were elevated in the MCD groups more than in the MHC group (p < 0.001). Time-averaged proteinuria and frequency of relapses during the follow-up period were higher in the high-intensity than in the low-intensity subgroup (1.18 ± 0.54 vs. 0.57 ± 0.45 g/day, p = 0.022; and 0.72 ± 0.60 vs. 0.09 ± 0.22 episodes/year, p = 0.022, respectively). Mitochondrial injury may be associated with MCD pathogenesis, and the signal intensity of STING IHC staining at the time of diagnosis could be used as a valuable prognostic marker in MCD.

ß-Defensin 2, an Antimicrobial Peptide, as a Novel Biomarker for Ulcerative Interstitial Cystitis; Can ß-Defensin 2 Suspect the Dysbiosis of Urine Microbiota?

As urine is not sterile, inflammatory reactions caused by dysbiosis of the urinary microbiota may induce interstitial cystitis. A study was conducted to determine whether ß-defensin 2 (BD-2), a specific antimicrobial peptide in the bladder, could be used as a novel diagnostic marker for ulcerative interstitial cystitis (IC). Urine samples from three female groups were examined: healthy controls (n = 34, Control group), non-Hunner type IC (n = 40, NHIC group), and Hunner type IC (n = 68, HIC group). Urine samples were collected via a transurethral catheter and assayed for BD-2 levels using enzyme linked immunosorbent assay. Under general or regional anesthesia, cystoscopy with diagnostic and therapeutic hydrodistension was performed in NHIC and HIC groups patients. These patients underwent a biopsy of the bladders. Based on the urinary specimens from 142 patients, BD-2 expression was found to be 18-fold higher in patients with Hunner type IC than in patients with non-Hunner type IC. The enhanced secretion of BD-2 exhibited a strong correlation with increased mast cell counts associated with bladder IC pathology. Enhanced urinary secretion of the antimicrobial peptide BD-2 from Hunner type IC patients associated with clinical phenotypes and demonstrated relatively robust levels to be used as a potential biomarker. Moreover, the increased urinary level of BD-2 may suggest a new possibility of biomarkers caused by dysbiosis of the urinary microbiota in ulcerative IC.

The Positive Correlations between the Expression of Histopathological Ubiquitin-Conjugating Enzyme 2O Staining and Prostate Cancer Advancement.

BACKGROUND: The mTOR signaling pathway is inactivated by AMPK's tumor-suppressing function. It is recognized that ubiquitin conjugating enzyme 2O (UBE2O), which directly targets AMPK for ubiquitination and degradation, is intensified in human cancers. METHODS: This study investigated the clinical data about prostate cancer. Examination was also carried out into tissue microarrays (TMA) of human prostate cancer (n = 382) and adjacent non-neoplastic tissues around prostate cancer (n = 61). The TMA slides were incubated with antibodies against UBE2O, and the cores were scored by the pathologist blind to cancer results. RESULTS: Very strong positive correlations were identified between the expression of UBE2O staining and high PSA and pathological stage of prostate cancer. Cox's proportional hazard analysis established correlations between the following: (1) positive surgical margin and biochemical recurrence free survival, (2) PSA grade and clinical recurrence free survival, (3) regional lymph node positive and clinical recurrence free survival, (4) adjuvant treatment and overall survival, and (5) pathological T stage and overall survival. CONCLUSION: There is a positive correlation between the expression of UBE2O staining and prognosis for prostate cancer. Thus, a prostate cancer prognosis can be assessed with the expression of UBE2O staining.

Malignant rhabdoid tumor of the kidney in an adult with loss of INI1 expression and mutation in the SMARCB1 gene.

A 57-year-old man with left flank pain was referred to our institute. Computed tomography scans revealed two enhancing masses in the left kidney. The clinical diagnosis was renal cell carcinoma (RCC). He underwent a radical nephrectomy with an adrenalectomy. Two well-circumscribed solid masses in the hilum and the lower pole (4.5 × 3.5 cm and 7.0 × 4.1 cm) were present. Poorly cohesive uniform round to polygonal epithelioid cells making solid sheets accounted for most of the tumor area. The initial diagnosis was RCC, undifferentiated with rhabdoid features. As the tumor showed loss of INI1 expression and a mutation in the SMARCB1 gene on chromosome 22, the revised diagnosis was a malignant rhabdoid tumor (MRT) of the kidney. To date, only a few cases of renal MRT in adults have been reported. To the best of our knowledge, this is the first report of MRT in the native kidney of an adult demonstrating a SMARCB1 gene mutation, a hallmark of MRT.

ERG and nestin: useful markers of immature vessels and novel prognostic markers in renal cell carcinoma.

OBJECTIVES: Renal cell carcinoma (RCC) accounts for approximately 90% of all renal malignancy. Because a rich vasculature is an outstanding feature of RCC, information on the blood vessels of RCC might explain its tumor characteristics. Several researchers have noted the effects of tumor vessels on the clinicopathologic characteristics and prognosis of tumors; however, a clear association has not been established. We hypothesized that the immaturity of the neovasculature may be an important clinicopathologic characteristic forprognosis of RCC patients. ERG and nestin are new vascular markers that regulate vascular homeostasis and angiogenesis. Therefore, in the present study, we investigated how ERG and nestin were expressed with respect to tumor characteristics. MATERIALS AND METHODS: IHC staining for ERG, nestin, CD31, and CD34 was performed for 217 renal tumors, including clear-cell RCC (ccRCC; n = 184), papillary RCC (pRCC; n = 14), chromophobe RCC (chRCC; n = 14), and oncocytoma (n = 5). RESULTS: Vascular endothelial cells from normal kidney consistently showed strong nuclear expression of ERG and nestin. Conversely, a loss of ERG and nestin expression was observed in endothelial cells of some tumor blood vessels, which was associated with tumor progression. In particular, the loss of ERG expression was significantly associated with progression-free survival and overall survival (univariate analyses: P = 0.027 and P = 0.004, respectively; multivariate analyses: P = 0.030 and P = 0.046, respectively). CONCLUSION: A loss of ERG and nestin expression is associated with tumor progression, and loss of ERG is a powerful prognostic marker for ccRCC.

Early Imaging Findings of Hypertrophic Osteoarthropathy Mimicking Bone Metastasis from Extrathoracic Malignancy.

Hypertrophic osteoarthropathy (HOA) is a syndrome characterized by digital clubbing, periosteal bone formation, and synovial effusions. Secondary HOA is associated with intrathoracic malignancy in most cases; however, in rare cases, HOA can be caused by extrathoracic conditions. We report early ultrasound, computed tomography, magnetic resonance imaging, and bone scintigraphy findings of HOA in a patient with breast cancer. Its ambiguous clinical and imaging findings that mimicked malignant conditions are particularly interesting and informative.

Spontaneous rupture of immature gastric teratoma with hemoperitoneum in a newborn with 3-year follow-up.

Among the subtypes of germ cell tumors, teratomas are the most frequent in the pediatric population and commonly occur in the sacrococcygeal region and the gonads. Less than 1% of all teratoma are found in abdominal organs including the stomach, liver, and kidney. Gastric teratomas are very rare tumors predominantly found in infants. Moreover, an immature gastric teratoma is exceptionally rare. Here, we present a case of immature gastric teratoma with spontaneous rupture in a newborn who was preoperatively diagnosed with neuroblastoma. On the first day after birth, the neonate presented with progressive abdominal distension accompanying respiratory distress. A firm mass was detected during a physical examination of the abdomen. An emergency exploratory laparotomy revealed hemoperitoneum resulting from a rupture of the tumor located in the posterior wall of the gastric antrum. Complete resection of the tumor and gastroduodenostomy were performed. The pathology evaluation revealed a grade 3 immature gastric teratoma with no malignant components. The patient was treated with adjuvant chemotherapy to prevent recurrence, since the tumor was ruptured in the abdominal cavity and the level of alpha-fetoprotein was decreased but still remained high above the normal range after surgery. In conclusion, physicians should be aware of the existence of gastric teratoma as the differential diagnosis of a huge abdominal mass in infants, especially neonates. Complete surgical removal of the tumor and long-term follow-up has been adopted as the standard management for immature gastric teratoma, although there has been controversy with adjuvant chemotherapy.

Intramuscular composite hemangioendothelioma: case report of an unusual tumor in an unusual location.

Composite hemangioendothelioma (CHE) is an extremely rare locally aggressive vascular neoplasm comprising various benign, intermediate, and malignant vascular components. It is usually located superficially, in the dermis and subcutis of the extremities. Herein, we report a first case of CHE arising from the skeletal muscle in a 67-year-old woman who presented with a palpable mass on her right forearm. Magnetic resonance imaging revealed a 3.0 × 2.7-cm intramuscular mass with high-signal intensity on contrast-enhanced T2-weighted images. Excision was performed, and microscopic examination revealed a heterogeneous mixture of vascular components, consisting of arteriovenous malformation, spindle cell hemangioma, retiform hemangioendothelioma, and angiosarcoma-like areas. Moreover, we present a brief review of previously reported cases of CHE arising from the extremities.

Multifocal ectopic thyroid tissues including breast: A case report.

The current study reports the case of multifocal ectopic thyroid tissues in the breast. Ectopic thyroid tissue is an uncommon entity found not only in the cysts of thyroglossal ducts, but also along the thyroglossal duct. The most frequent location of this tissue is the base of the tongue, but they can also occur in the anterior tongue, submandibular or sublingual region, larynx, trachea, mediastinum and heart. Only a single case of ectopic thyroid tissue in breast has been previously reported in English literature. However, the current case was associated with abnormal embryological development compared with previous reports, which are attributed to abnormal implantation.

Minor Glomerular Abnormalities are Associated with Deterioration of Long-Term Kidney Function and Mitochondrial Injury.

Minor glomerular abnormalities (MGAs) are unclassified glomerular lesions indicated by the presence of minor structural abnormalities that are insufficient for a specific pathological diagnosis. The long-term clinical outcomes and pathogenesis have not been examined. We hypothesized that MGAs would be associated with the deterioration of long-term kidney function and increased urinary mitochondrial DNA (mtDNA) copy numbers. We retrospectively enrolled patients with MGAs, age-/sex-/estimated glomerular filtration rate (eGFR)-matched patients with immunoglobulin A nephropathy (IgAN), and similarly matched healthy controls (MHCs; n = 49 each). We analyzed the time × group interaction effects of the eGFR and compared mean annual eGFR decline rates between the groups. We prospectively enrolled patients with MGAs, age- and sex-matched patients with IgAN, and MHCs (n = 15 each) and compared their urinary mtDNA copy numbers. Compared to the MHC group, the MGA and IgAN groups displayed differences in the time × group effects of eGFR, higher mean annual rates of eGFR decline, and higher urinary mtDNA copy numbers; however, these groups did not significantly differ from each other. The results indicate that MGAs are associated with deteriorating long-term kidney function, and mitochondrial injury, despite few additional pathological changes. We suggest that clinicians conduct close long-term follow-up of patients with MGAs.

Loss of Nuclear BAP1 Expression Is Associated with High WHO/ISUP Grade in Clear Cell Renal Cell Carcinoma.

BACKGROUND: BRCA1-associated protein 1 (BAP1) mutations are frequently reported in clear cell renal cell carcinoma (ccRCC); however, very few studies have evaluated the role of these mutations in other renal cell carcinoma (RCC) subtypes. Therefore, we analyzed BAP1 protein expression using immunohistochemistry in several RCC subtypes and assessed its relationship with clinicopathological characteristics of patients. METHODS: BAP1 expression was immunohistochemically evaluated in tissue microarray blocks constructed from 371 samples of RCC collected from two medical institutions. BAP1 expression was evaluated based on the extent of nuclear staining in tumor cells, and no expression or expression in < 10% of tumor cells was defined as negative. RESULTS: Loss of BAP1 expression was observed in ccRCC (56/300, 18.7%), chromophobe RCC (6/26, 23.1%), and clear cell papillary RCC (1/4, 25%), while we failed to detect BAP1 expression loss in papillary RCC, acquired cystic disease-associated RCC, or collecting duct carcinoma. In ccRCC, loss of BAP1 expression was significantly associated with high World Health Organization (WHO)/International Society of Urological Pathology (ISUP) grade (p = .002); however, no significant correlation was observed between loss of BAP1 expression and survival in ccRCC. Loss of BAP1 expression showed no association with prognostic factors in chromophobe RCC. CONCLUSIONS: Loss of BAP1 nuclear expression was observed in both ccRCC and chromophobe RCC. In addition, BAP1 expression loss was associated with poor prognostic factors such as high WHO/ISUP grade in ccRCC.

Gene copy number variation and protein overexpression of EGFR and HER2 in distal extrahepatic cholangiocarcinoma.

EGFR and HER2 are among the most promising therapeutic targets in solid cancers. The expression status of EGFR and HER2 are associated with the prognosis, and with a number of clinicopathological factors, in many cancers. However, few studies have examined this association in distal extrahepatic cholangiocarcinoma (EHCC). Therefore, we investigated EGFR and HER2 protein expression and gene copy number variation (CNV) in distal EHCC. We also studied the association of these factors with clinicopathological parameters and prognosis. Immunostaining, using antibodies against EGFR and HER2, was performed on 84 cases of distal EHCC. All positive (3+) and equivocal (2+) EGFR and HER2 expression cases, together with randomly selected negative (1+ and 0) cases, were evaluated for EGFR and HER2 CNV. Among distal EHCC samples, 6.0% (n=5) were positive (3+) for EGFR expression and 6.0% (n=5) were equivocal (2+). HER2 expression was positively identified in 2.4% of samples (n=2), and was equivocal in 1.2% of samples (n=1). All cases of positive EGFR expression showed amplification (n=1) or high polysomy (n=4) involving the EGFR gene; three cases (60%) of equivocal EGFR expression showed high polysomy of the EGFR gene. All cases of positive or equivocal HER2 expression (n=3, 3.6%) showed amplification of the HER2 gene. In univariate analysis, EGFR expression and CNV were associated with shorter cancer-specific overall survival (p=0.003 and p=0.018, respectively). Multivariate analysis also showed that EGFR CNV was a significant prognostic factor in distal EHCC (p=0.015). Although further study is warranted, our findings suggest that EGFR expression and CNV are factors associated with poor prognosis, and that anticancer therapeutics against EGFR and HER2 receptors may be promising therapeutic options for patients with distal EHCC.

Downregulation of osteoprotegerin expression in metastatic colorectal carcinoma predicts recurrent metastasis and poor prognosis.

We recently reported the downregulation of osteoprotegerin expression in primary colorectal carcinoma and its significant association with aggressive oncogenic behavior, which suggest that this process contributes to colorectal carcinoma development and progression. In this study, we used immunohistochemical staining to evaluate osteoprotegerin expression in 81 colorectal liver metastasis tissue samples and investigated its possible association with the clinicopathological characteristics and outcomes of patients with colorectal liver metastasis. These tissues exhibited significantly reduced expression of osteoprotegerin compared to primary colorectal carcinomas and normal colorectal mucosa. This reduced expression was significantly associated with the extent of colorectal liver metastasis, including multiplicity of metastatic tumors, involvement of the bilateral hepatic lobes, and higher histological grade. In addition, reduced osteoprotegerin expression was an independent significant predictor of recurrent liver metastasis and prognostic factor for reduced patient survival. These findings suggest that osteoprotegerin expression may be a novel predictor of recurrent liver metastasis and a prognostic biomarker in patients with colorectal liver metastasis. Patients harboring colorectal liver metastasis with reduced osteoprotegerin expression should be carefully monitored after hepatic resection for colorectal liver metastasis to enable early detection of potentially resectable metastatic recurrences.