Monosomy 3 by chromogenic in situ hybridization (CISH) in Iranian patients with uveal melanoma

Purpose: The aim of this study was to investigate the rate of monosomy 3 by CISH technique in Iranian patients with uveal melanoma (UM) and its correlation with clinical and histopathological features. Method: Archival formalin fixed, paraffin-embedded material from 50 patients who had undergone enucleation for large uveal melanomas was obtained. Monosomy of chromosome 3 alteration by chromogenic in situ hybridization (CISH) was investigated. Clinical and histopathological features of tumors were collected. Results: The patients had a mean age of 56.6±7.6 years. Mean basal diameter and thickness of tumors were 14.1 mm and 10.2 mm, respectively. Four patients (8) were identified to harbor monosomy of chromosome 3. In the mean follow-up of 5.3 years (range, 3.2-9.5 y), only one case with monosomy 3 died of UM metastasis. The most common type of cellularity was mixed cell (86).There was not any statistically significant correlation between monosomy of chromosome 3 and type of cellularity, ciliary body involvement, and largest basal diameter. Conclusion: The low rate of monosomy chromosome 3 and the consequent low rate of mortality may be indicative of good prognosis in Iranian patients with uveal melanoma. © 2015 Iranian Society of Ophthalmology

Clinicopathological significance of tumor stem cell markers aldh1 and CD133 in colorectal carcinoma

Background & Objective: Colorectal cancer (CRC) is the third most common cancer worldwide with a high mortality rate. The main causes of death in patients are recurrence and metastasis which are mainly attributed to the small subpopulation of cells within tumors called cancer stem cells (CSCs). This study aimed to evaluate the correlation between the expression of ALDH1 and CD133 as CSC associated markers and clinicopathological characteristics in CRC. Methods: In this cross-sectional study, a total of 483 CRC tumor samples were immunohistochemically stained for detection of CD133 and ALDH1 markers. Correlations of marker expression with clinicopathological factors were also evaluated. Results: There was a significant correlation between the luminal intensity of CD133 and neural invasion (P=0.05) and between the cytoplasmic intensity of CD133 and metastasis (P=0.05). In terms of H-score, a positive significant relation was observed between cytoplasmic expression of CD133 and lymph node (P=0.02), neural (P=0.04) and vascular invasion (P=0.02). The ALDH1 cytoplasmic expression showed a significant correlation with tumor size (P=0.001). Conclusion: Our findings showed that increased expression of CD133 and ALDH1 is associated with tumor progression and worse outcomes in CRC patients. These markers can be good candidates for localized targeting of CSCs using antibodies. Future researches need to be improved approaches for early detection of CRC, and treatment monitoring for CRC and other cancers. © 2021, Iranian Society of Pathology. All rights reserved

Common bile duct stone associated with hemolytic uremic syndrome

Cholelithiasis is an unusual complication of hemolytic uremic syndrome. A 12-year-old boy with hemolytic uremic syndrome, established by renal biopsy, who developed cholestatic jaundice is presented here. Laboratory results for secondary causes of hemolytic uremic syndrome were normal. Abdominal ultrasonography and magnetic resonance cholangiopancreatography revealed extrahepatic obstruction. A common bile duct stone, discovered by retrograde cholanglopancreatography was extracted by sphincterotomy. In conclusion, cholelithiasis should be considered as a cause of abdominal pain and cholestasis in patients who are diagnosed as having hemolytic uremic syndrome

Co-expression of Cancer Stem Cell Markers OCT4 and NANOG Predicts Poor Prognosis in Renal Cell Carcinomas

Many renal cancer patients experience disease recurrence after combined treatments or immunotherapy due to permanence of cancer stem cells (CSCs). This study was conducted to evaluate the expression patterns and clinical significance of octamer-binding transcription factor 4 (OCT4) and NANOG as the key stem cell factors in renal cell carcinoma (RCC). A total of 186 RCC tissues were immunostained on a tissue microarray (TMA) for the putative CSC markers OCT4 and NANOG. Subsequently, the correlation among the expression of these markers, the clinicopathological variables and survival outcomes were determined. OCT4 and NANOG were expressed in both the nucleus and the cytoplasm of RCC cells. Coexpression of OCT4 and NANOG in renal cancer was significantly associated with RCC subtypes. A significant association was found among nuclear coexpression of OCT4 and NANOG, worse PFS in RCC, and the clear cell renal cell carcinomas (ccRCC) subtype. The OCT4-nuclear high/NANOG-nuclear high phenotype in RCC and ccRCC subtype indicated aggressive tumor behavior and predicted a worse clinical outcome, which may be a useful biomarker to identify patients at high risk of postoperative recurrence and metastasis. Cytoplasmic expression of NANOG could be considered as a novel independent prognostic predictor in patients with renal cancer. © 2018, The Author(s)

Human telomerase reverse transcriptase protein expression predicts tumour aggressiveness and survival in patients with clear cell renal cell carcinoma

Human telomerase reverse transcriptase (hTERT) is an active component of telomerase and responsible for its catalytic activity, associated with cell proliferation and differentiation. For the first time, the present study was conducted to evaluate the expression and prognostic significance of hTERT in different histological subtypes of renal cell carcinoma (RCC). Expression of hTERT was examined in 176 well-defined renal tumour samples including clear cell RCCs (ccRCCs), papillary and chromophobe RCCs using immunohistochemistry on tissue microarrays. The association between hTERT expression and clinicopathological parameters as well as survival outcomes were then analysed. There was a statistically significant difference in terms of hTERT expression among various RCC subtypes. In ccRCC, increased expression of hTERT was significantly associated with advanced stage, higher grade, presence of microvascular invasion, lymph node invasion, and metastasis. Moreover, in the multivariate analysis, tumour stage and tumour size were independent predictors of the disease-specific survival (DSS). Additionally, expression of hTERT was found to be a significant predictor of worse DSS (p = 0.012) in the univariate analysis. In papillary carcinoma samples (type I and II), significant association was detected between hTERT expression and the tumour stage (p = 0.010, p = 0.050), respectively. In chromophobe RCC, no significant association was detected between expression of hTERT and clinicopathological parameters and survival data. We showed that hTERT protein expression was associated with more aggressive tumour behaviour and more advanced disease in ccRCC patients. Also, hTERT may be a novel poor prognostic indicator of DSS, if the patients are followed for more prolonged time periods. © 2018 Royal College of Pathologists of Australasi

High expression of DNA damage-inducible transcript 4 (DDIT4) is associated with advanced pathological features in the patients with colorectal cancer

DNA damage-inducible transcript 4 (DDIT4) is induced in various cellular stress conditions. This study was conducted to investigate expression and prognostic significance of DDIT4 protein as a biomarker in the patients with colorectal cancer (CRC). PPI network and KEGG pathway analysis were applied to identify hub genes among obtained differentially expressed genes in CRC tissues from three GEO Series. In clinical, expression of DDIT4 as one of hub genes in three subcellular locations was evaluated in 198 CRC tissues using immunohistochemistry method on tissue microarrays. The association between DDIT4 expression and clinicopathological features as well as survival outcomes were analyzed. Results of bioinformatics analysis indicated 14 hub genes enriched in significant pathways according to KEGG pathways analysis among which DDIT4 was selected to evaluate CRC tissues. Overexpression of nuclear DDIT4 protein was found in CRC tissues compared to adjacent normal tissues (P = 0.003). Furthermore, higher nuclear expression of DDIT4 was found to be significantly associated with the reduced tumor differentiation and advanced TNM stages (all, P = 0.009). No significant association was observed between survival outcomes and nuclear expression of DDIT4 in CRC cases. Our findings indicated higher nuclear expression of DDIT4 was significantly associated with more aggressive tumor behavior and more advanced stage of disease in the patients with CRC. © 2021, The Author(s)

The value of serum uric acid as a mortality prediction in critically ill children

Objective: The role of initial serum uric acid on admission in critically ill patients is controversial; we presumed that uric acid level can predict the mortality of the admitted patients to intensive care unit as a simple test. Methods: Totally, 220 consecutively admitted children (96 girls, 124 boys) with mean age 3.5 years, who were at least 24 hours in pediatric intensive care unit (PICU), were enrolled in a prospective cohort study during January 2006 to December 2007. The subsequent PICU admission in the same hospitalization, those who were discharged from the hospital and then re-admitted to the PICU during the observation period, and the patients with chronic renal failure were excluded. Serum uric acid level was measured during the first day of PICU admission. Death or transfer from PICU was considered as final outcome. The statistical analysis was done by using linear regression analysis, ROC curve, Student t-test, and Chisquare. P value less than 0.05 was considered significant. Findings: From 44 patients who had serum uric acid level more than 8 mg/dl, 17 cases died showing with a higher relative risk of 1.88, higher mortality (P8 mg/dl and needed vasopressor was 1.04, and in those under mechanical ventilation 1.33. In patients who scored pediatric risk of mortality of >38 it was 1.4, and in septic cases 4 (P<0.05). Stepwise linear regression analysis showed that mainly the need for mechanical ventilation (P=0.001) and vasopressor had statistically significant correlation with the poor outcome (P=0.001). Conclusion: Uric acid level during the first day of intensive critical care admission is not an independent risk of mortality in PICU. Need for mechanical ventilation or inotropic agents was associated with poor outcome and only higher uric acid level in sepsis played an additive risk factor role. © 2010 by Pediatrics Center of Excellence, Children's Medical Center, Tehran University of Medical Sciences

Massive Spontaneous Hemothorax Associated With Von Recklinghausen's Disease

A 30-year-old woman with Von Recklinghausen's disease was admitted to our hospital because of sudden onset of dyspnea and syncope. A chest roentgenogram showed a massive right pleural effusion and insertion of an intercostal tube drained 1,600 cc of blood. A computed tomographic chest scan with contrast revealed a hyperdense mass in the right paravertebral area. At thoracotomy, retained clotted hemothorax and continued bleeding from tumor vessels was noted. The apex of the right hemithorax and the tumor location was packed. The pathologic diagnosis was ganglioneuroma and follow-up of the patient for 2 years after re-thoracotomy and removal of the packs revealed no complication and morbidity. We report this case to emphasize the importance of early recognition and prompt surgical intervention in spontaneous hemothorax associated with Von Recklinghausen's disease. © 2006 The Society of Thoracic Surgeons

Tumor infiltrating cytotoxic CD8 T-Cells predict clinical outcome of neuroblastoma in children

Context: Neuroblastoma is often infiltrated by inflammatory cells, particularly macrophages and T lymphocytes, but the significance of these cells remains unclear. One possible role of these inflammatory cells is that they represent a cell-mediated immune response against cancer. CD8+ lymphocytes are a known crucial component of cell-mediated immunity. The purpose of this study was to explore the prognostic value of tumor-infiltrating CD8+ cytotoxic lymphocytes in Neuroblastoma. Subjects and Methods: Tumor-infiltrating CD8+ lymphocytes were assessed by immunohistochemical staining of tumor tissue from 36 neuroblastoma from April 2008 to May 2015. The number of CD8+ T-cells was counted in tumor nest (intratumoral) and in the fibrovascular stroma of tumor (peritumoral), and their relationship with clinicopathologic outcome was determined. Results: The total number of CD8+ cells was inversely correlated with tumor histology grade (P < 0.001), vascular invasion (P < 0.001), capsular invasion (P < 0.002), calcification (P < 0.005), necrosis of tumor (P < 0.001), regional lymph nodes invasion (P < 0.003), distant metastasis (P < 0.003), stage (P < 0.003), and was positive correlated with N-myc oncogene presentation (P < 0.002) in neuroblastoma. However, there were no correlation between patient's age, sex, and size of tumor with infiltration of CD8+ cells (P < 0.097, P < 0.142, and P < 0.722, respectively). Conclusions: In this analysis, total CD8 T-cell count was a dependent prognostic factor in children. Total number and stromal CD8 lymphocytes were associated with better patient survival (P < 0.003 and P < 0.05, respectively) in children. These results suggest that tumor-infiltrating CD8 T lymphocytes have antitumor activity and influence the behavior of neuroblastoma and might be potentially be exploited in the treatment of neuroblastoma in children. © 2018 Indian Journal of Medical and Paediatric Oncology Published by Wolters Kluwer - Medknow