Single omental metastasis of renal cell carcinoma after radical nephrectomy: A case report.

BACKGROUND: Renal cell carcinoma (RCC) is the third most common malignancy in the genitourinary tract. The lungs, bone, lymph nodes, liver, and brain are common metastatic sites of RCC. However, there is limited literature on single omental metastasis of RCC. CASE SUMMARY: We present the case of a 44-year-old man with single omental metastasis of RCC after laparoscopic radical nephrectomy. Pathological diagnosis of the resected left kidney revealed pT3a clear cell RCC (Fuhrman grade III). At 6 mo postoperatively, abdominal computed tomography revealed a 12-mm enhancing nodule in the left lower peritoneum. At 7 mo after initial operation, laparoscopic removal of the left omental nodule was performed. The pathological results indicated metastatic clear cell RCC. Currently, the patient is being treated with adjuvant pembrolizumab. CONCLUSION: Omental metastasis of RCC owing to laparoscopic radical nephrectomy is rare. Urologists should be aware of the diverse nature of RCC.

Identification of a novel non-invasive biological marker to overcome the shortcomings of PSA in diagnosis and risk stratification for prostate cancer: Initial prospective study of developmental endothelial locus-1 protein.

OBJECTIVE: This prospective study sought to clarify the developmental endothelial locus-1 (Del-1) protein as values of diagnosis and risk stratification of prostate cancer (PCa). DESIGN: From February 2017 to December 2019, a total 458 patients who underwent transrectal ultrasound guided prostate biopsy or surgery of benign prostatic hyperplasia agreed to research of Del-1 protein. We prospectively compared and analyzed the Del-1 protein and prostate specific antigen (PSA) in relation to the patients' demographic and clinicopathological characteristics. RESULTS: Mean age was 68.86±8.55 years. Mean PSA and Del-1 protein was 21.72±89.37, 0.099±0.145, respectively. Two hundred seventy-six (60.3%) patients were diagnosed as PCa. Among them, 181 patients underwent radical prostatectomy (RP). There were significant differences in Del-1 protein between benign and PCa group (0.066±0.131 vs 0.121±0.149, respectively, p<0.001). When we set the cut-off value of del-1 protein as 0.120, in patients with 3≤PSA≤8, positive predictive value and specificity of Del-1 protein (≥0.120) for predicting PCa were 88.9% (56/63) and 93.5% (101/108), respectively. Among 181 patients who underwent RP, there were significant differences in Del-1 protein according to stage (pT2 vs pT3a vs ≥pT3b) (0.113±0.078, 0.171±0.121, 0.227±0.161, respectively, p<0.001) and to Gleason score (6 (3+3) or 7 (3+4) vs 7 (4+3) or 8 (4+4) vs 9 or 10) (0.134±0.103, 0.150±0.109, 0.212±0.178, respectively, P = 0.044). Multivariate analysis showed that PSA, Del-1 protein and high Gleason score (≥9) were the independent prognostic factors for predicting higher pT stage (≥3b). Furthermore, age, PSA and Del-1 protein were independent prognostic factors for predicting significant PCa. CONCLUSION: Patients with PCa showed higher expression of Del-1 protein than benign patients. Del-1 protein increased with the stage and Gleason score of PCa. Collaboration with PSA, Del-1 protein can be a non-invasive useful marker for diagnosis and risk stratification of PCa.

A rare pericytic tumor of the kidney: The first case in Korea.

INTRODUCTION: A pericytic tumor is a group of mesenchymal neoplasm found in superficial tissues and only rarely described in viscera. The family of pericytic tumors includes glomus tumors and variants, myopericytoma including myofibroma, and angioleiomyoma etc. The renal pericytic tumor is extremely rare, and only few comprehensive discussions about this entity have been done. PRESENTATION OF CASE: A 58-year-old man was transferred to our institute with suspicions of renal cell carcinoma. The kidney dynamic computed tomography scan showed a 3 cm sized solid mass in the upper pole of the right kidney. Laparoscopic radical nephrectomy was performed due to the deep-seated mass. Pathological result confirmed that the kidney mass was renal pericytic tumor. DISCUSSION: Although general biological behavior of published renal pericytic tumors is likely to be benign, the clinicopathologic experiences are very limited. Therefore, we should evaluate the malignant potential of the entity according to the parameters proposed for soft tissue tumors, including tumor location, tumor size, growth pattern, cellularity, cytological atypia, and mitotic figures with atypical forms. The current case shows several worrisome features, including an extremely rare tumor location, partially infiltrative growth, and a mildly increased proliferating index, which resulted in it being classified as an uncertain malignant potential. CONCLUSION: We described the first case of renal pericytic tumor, addressing uncertain malignant potential, in a Korean male, which would be a distinct mesenchymal neoplasm differentiating from other groups of perivascular tumor families based on histological and immunohistochemical features.

Clinical significance of the De Ritis ratio for detecting prostate cancer in a repeat prostate biopsy.

Purpose: We evaluated factors predicting a positive repeat biopsy result in patients with an initial negative prostate biopsy result. Materials and Methods: This study included 124 patients in whom prostate cancer (PCa) was not detected in the initial transrectal ultrasound-guided prostate biopsy and who underwent repeat biopsy from January 2011 to December 2017. Patients without PCa in both initial and repeat prostate biopsies were designated as group 1 (n=82), and those in whom PCa was detected on a repeat prostate biopsy were designated as group 2 (n=42). Among group 2 patients, 6 had insignificant PCa according to the Epstein criteria and were combined with group 1 patients to make up group A (n=88). Patients with significant PCa were categorized as group B (n=36). We compared clinicopathologic characteristics between the groups. Results: Multivariate analysis showed that age (p=0.018) and detection of atypical small acinar proliferation (ASAP) or ≥3 cores of high-grade prostatic intraepithelial neoplasia (HGPIN) (p=0.011) on the initial biopsy were predictive factors for a positive result on a repeat biopsy. When we compared group A and group B, age (p=0.004) and the De Ritis ratio (p=0.024) were significantly higher in group B in the multivariate analysis. Conclusions: Age and the detection of ASAP or ≥3 cores of HGPIN on the initial biopsy were associated with detection of PCa on a repeat biopsy. Age and the De Ritis ratio were found to be predictive factors for the detection of clinically significant PCa on a repeat biopsy.

ZNF492 and GPR149 methylation patterns as prognostic markers for clear cell renal cell carcinoma: Array­based DNA methylation profiling.

The present study aimed to identify novel methylation markers of clear cell renal cell carcinoma (ccRCC) using microarray methylation analysis and evaluate their prognostic relevance in patient samples. To identify cancer­specific methylated biomarkers, microarray profiling of ccRCC samples from our institute (n=12) and The Cancer Genome Atlas (TCGA) database (n=160) were utilized, and the prognostic relevance of candidate genes were investigated in another TCGA dataset (n=153). For validation, pyrosequencing analyses with ccRCC samples from our institute (n=164) and another (n=117) were performed and the potential clinical application of selected biomarkers was examined. We identified 22 CpG island loci that were commonly hypermethylated in ccRCC. Kaplan­Meier analysis of TCGA data indicated that only 4/22 loci were significantly associated with disease progression. In the internal validation set, Kaplan­Meier analysis revealed that hypermethylation of two loci, zinc finger protein 492 (ZNF492) and G protein­coupled receptor 149 (GPR149), was significantly associated with shorter time­to­progression. Multivariate Cox regression models revealed that hypermethylation of ZNF492 [hazard ratio (HR), 5.44; P=0.001] and GPR149 (HR, 7.07; P<0.001) may be independent predictors of tumor progression. Similarly, the methylation status of these two genes was significantly associated with poor outcomes in the independent external validation cohort. Collectively, the present study proposed that the novel methylation markers ZNF492 and GPR149 could be independent prognostic indicators in patients with ccRCC.

A Novel Orally Active Inverse Agonist of Estrogen-related Receptor Gamma (ERRγ), DN200434, A Booster of NIS in Anaplastic Thyroid Cancer.

PURPOSE: New strategies to restore sodium iodide symporter (NIS) expression and function in radioiodine therapy-refractive anaplastic thyroid cancers (ATCs) are urgently required. Recently, we reported the regulatory role of estrogen-related receptor gamma (ERRγ) in ATC cell NIS function. Herein, we identified DN200434 as a highly potent (functional IC50 = 0.006 µmol/L), selective, and orally available ERRγ inverse agonist for NIS enhancement in ATC. EXPERIMENTAL DESIGN: We sought to identify better ERRγ-targeting ligands and explored the crystal structure of ERRγ in complex with DN200434. After treating ATC cells with DN200434, the change in iodide-handling gene expression, as well as radioiodine avidity was examined. ATC tumor-bearing mice were orally administered with DN200434, followed by 124I-positron emission tomography/CT (PET/CT). For radioiodine therapy, ATC tumor-bearing mice treated with DN200434 were administered 131I (beta ray-emitting therapeutic radioiodine) and then bioluminescent imaging was performed to monitor the therapeutic effects. Histologic analysis was performed to evaluate ERRγ expression status in normal tissue and ATC tissue, respectively. RESULTS: DN200434-ERRγ complex crystallographic studies revealed that DN200434 binds to key ERRγ binding pocket residues through four-way interactions. DN200434 effectively upregulated iodide-handling genes and restored radioiodine avidity in ATC tumor lesions, as confirmed by 124I-PET/CT. DN200434 enhanced ATC tumor radioiodine therapy susceptibility, markedly inhibiting tumor growth. Histologic findings of patients with ATC showed higher ERRγ expression in tumors than in normal tissue, supporting ERRγ as a therapeutic target for ATC. CONCLUSIONS: DN200434 shows potential clinical applicability for diagnosis and treatment of ATC or other poorly differentiated thyroid cancers.

Oncological and functional outcomes following robot-assisted laparoscopic radical prostatectomy at a single institution: a minimum 5-year follow-up.

Background: To evaluate mid-term oncological and functional outcomes in patients with prostate cancer treated by robot-assisted laparoscopic radical prostatectomy (RALP) at our institution. Methods: We retrospectively reviewed the medical records of 128 patients with prostate cancer who underwent RALP at our institution between February 2008 and April 2010. All patients enrolled in this study were followed up for at least 5 years. We analyzed biochemical recurrence (BCR)-free survival using a Kaplan-Meier survival curve analysis and predictive factors for BCR using multivariate Cox regression analysis. Continence recovery rate, defined as no use of urinary pads, was also evaluated. Results: Based on the D'Amico risk classification, there were 30 low-risk patients (23.4%), 47 intermediate-risk patients (38.8%), and 51 high-risk patients (39.8%), preoperatively. Based on pathological findings, 50.0% of patients (64/128) showed non-organ confined disease (≥T3a) and 26.6% (34/128) had high grade disease (Gleason score ≥8). During a median follow-up period of 71 months (range, 66-78 months), the frequency of BCR was 33.6% (43/128) and the median BCR-free survival was 65.9 (0.4-88.0) months. Multivariate Cox regression analysis revealed that high grade disease (Gleason score ≥8) was an independent predictor for BCR (hazard ratio=4.180, 95% confidence interval=1.02-17.12, p=0.047). In addition, a majority of patients remained continent following the RALP procedure, without the need for additional intervention for post-prostatectomy incontinence. Conclusion: Our study demonstrated acceptable outcomes following an initial RALP procedure, despite 50% of the patients investigated demonstrating high-risk features associated with non-organ confined disease.

The Combination of Periostin Overexpression and Microvascular Invasion Is Related to a Poor Prognosis for Hepatocellular Carcinoma.

BACKGROUND/AIMS: Periostin is an extracellular matrix protein and is known to be related to the metastatic potential and prognosis of cancer. However, few studies have investigated the expression level of periostin and its association with prognoses in hepatocellular carcinoma. Therefore, we analyzed periostin overexpression in hepatocellular carcinoma and its implication for prognoses. METHODS: We evaluated 149 patients who underwent surgical resection between 2006 and 2010. Tissue microarrays were constructed from hepatocellular carcinoma tissue and adjacent nontumor tissue, and immunohistochemistry was performed. RESULTS: A high periostin level was observed more frequently in cases of multiple tumors (odds ratio [OR], 2.826; 95% confidence interval [CI], 1.224 to 6.527; p=0.013), positive microvascular invasion (OR, 2.974; 95% CI, 1.431 to 6.181; p=0.003), and advanced stage disease (OR, 3.032; 95% CI, 1.424 to 6.452; p=0.003). Patients with high periostin expression had significantly (p=0.002) lower overall survival rates than those with low periostin expression (90.3%, 66.1%, and 56.2% vs 97.7%, 85.1%, and 77.5% at 1, 3, and 5 years). CONCLUSIONS: We found that a combination of periostin overexpression and microvascular invasion in hepatocellular carcinoma was correlated with a poor prognosis and can be a good prognostic marker for hepatocellular carcinoma.

A Guide to Studying Human Hair Follicle Cycling In Vivo.

Hair follicles (HFs) undergo lifelong cyclical transformations, progressing through stages of rapid growth (anagen), regression (catagen), and relative "quiescence" (telogen). Given that HF cycling abnormalities underlie many human hair growth disorders, the accurate classification of individual cycle stages within skin biopsies is clinically important and essential for hair research. For preclinical human hair research purposes, human scalp skin can be xenografted onto immunocompromised mice to study human HF cycling and manipulate long-lasting anagen in vivo. Although available for mice, a comprehensive guide on how to recognize different human hair cycle stages in vivo is lacking. In this article, we present such a guide, which uses objective, well-defined, and reproducible criteria, and integrates simple morphological indicators with advanced, (immuno)-histochemical markers. This guide also characterizes human HF cycling in xenografts and highlights the utility of this model for in vivo hair research. Detailed schematic drawings and representative micrographs provide examples of how best to identify human HF stages, even in suboptimally sectioned tissue, and practical recommendations are given for designing human-on-mouse hair cycle experiments. Thus, this guide seeks to offer a benchmark for human hair cycle stage classification, for both hair research experts and newcomers to the field.

Target molecule expression profiles in metastatic renal cell carcinoma: Development of individual targeted therapy.

The aim of this study is to analyze the level of target molecule expression in metastatic renal cell carcinoma (RCC) to determine whether there is a correlation between molecular marker expression and clinical response. Ten patients with metastatic RCC, who received receptor tyrosine kinase (RTK) targeted therapy after cytoreductive or radical nephrectomy, were included. The expression of target molecules relating to the RTK, mammalian target of rapamycin, hypoxia inducible factor, mitogen activated protein kinase, and adenosine monophosphate-activated protein kinase pathways were analyzed using real-time polymerase chain reaction and immunohistochemistry. We correlated the level of target molecule expression with clinical response, including efficacy and adverse events experience during RTK targeted therapy. All patients showed similar histological subtype and grade on pathological examination; however, the expression of RCC target molecules was very different among the patients. The expression of molecules related to the RTK pathway in RCC tissue as well as relative expression of molecules in RCC tissue compared to normal kidney tissue, were higher in patients who showed a good response to RTK targeted therapy compared to those that showed a poor response. Target molecule expression in normal kidney tissue was higher in patients who experienced high-grade adverse events than in patients who experienced low-grade events. Target molecule expression in metastatic RCC correlates with targeted therapy clinical response including efficacy and adverse events. Personalized target molecule expression profiles could be used to predict clinical response to different targeted therapies, thus helping optimization of targeted therapies for patients with metastatic RCC.

Clinical Implication of Serine Metabolism-Associated Enzymes in Colon Cancer.

PURPOSE: Recently, enzymes of the serine synthetic pathway (SSP) have been suggested as key player in the metabolic adaptation of oncogenesis. We assessed the expression of enzymes of the SSP in colonic tumor tissue (TT) and paired normal tissue (pNT) and the prognostic implications. METHODS: From 2006 to 2010, we included 486 patients with colon cancer who underwent curative surgery at Kyungpook National University Hospital. Phosphoglycerate dehydrogenase (PHGDH), pyruvate dehydrogenase kinase (PDK) 1, PDK2, pyruvate kinase M2 (PKM2), and phosphoserine aminotransferase (PSAT) expression were investigated by immunohistochemical staining (IHC) in TT and pNT. The IHC values were calculated by multiplying intensity by proportion. The final score was classified as follows: 0-2 as negative and 3-12 as positive. RESULTS: During the median follow-up duration of 55.5 months (37.4-90.6), 78 patients experienced recurrence. The expression of PHGDH, PDK1, and PSAT was significantly higher in TT than pNT (p < 0.001 for each). The univariate analysis for relapse-free survival revealed that TT PDK2 positivity was the only positive prognostic factor (p = 0.023). However, the expression of TT PDK2 did not represent a prognostic value in multivariate analysis. CONCLUSIONS: In conclusion, PHGDH, PDK1, and PSAT were significantly increased in colonic TT compared with pNT. The prognostic implication of these enzymes needs to be further investigated.

Colorectal cancer-derived tumor spheroids retain the characteristics of original tumors.

Primary cultures of cancer cells are useful for developing personalized medicine. In this study, we characterized three lines of three-dimensional (3D) tumor spheroids established directly from tumor tissues of patients with colorectal cancers (CRCs). Each line mainly included EpCAM-positive cells and cells expressing putative cancer stem cell markers such as CD133, CD44, CD24, ALDH1, and LGR5. These characteristic stem cell markers remained identically for months in vitro. Short tandem repeat genotyping suggested that genetic fingerprints of these tumor spheroids were similar to those of the original tumor tissues from which they were derived. Mutational analysis showed that each line had the same mutation profile for APC, KRAS, MLH1, serine-threonine kinase 11, and TP53 as its parental tumor tissue. One line harboring an activating KRAS mutation was resistant to cetuximab while the remaining two lines harboring wild-type KRAS showed different responses to cetuximab. Immunohistochemical analysis showed that xenograft tumors derived from these lines retained the histopathological and mutational patterns of their parental tumors. Collectively, these results clearly showed that 3D tumor spheroids directly generated from tumor tissues of patients with CRCs preserved the characteristics of their parental tumor tissues and could be used for developing personalized medicines for CRCs.

Expression of aquaporin-1, aquaporin-3, and aquaporin-5 correlates with nodal metastasis in colon cancer.

OBJECTIVES: The clinical significance of aquaporin-1 (AQP1), aquaporin-3 (AQP3), and aquaporin-5 (AQP5) expression was analyzed in a large number of patients with colon cancer. METHODS: AQP1, AQP3, and AQP5 expression was investigated based on the immunohistochemistry of tissue microarray specimens from 486 colon cancer patients who underwent curative surgery. Scores were given to the staining intensity and percentage of positive cells, and the staining score was defined as the sum of these scores then used to categorize the AQP expression as negative, weakly AQP-positive, or strongly AQP-positive. RESULTS: A total of 298 (61.3%) patients were identified as strongly AQP1-positive (staining score ≥ 6), while 38 (7.8%) were strongly AQP3-positive and 145 (29.8%) were strongly AQP5-positive. The overexpression of AQP1, AQP3, and AQP5 was significantly correlated with lymph node metastasis in a multivariate logistic analysis (AQP1, p = 0.026; AQP3, p = 0.023; AQP5, p = 0.003). While the multivariate survival analysis, which included age, histology, TNM stage, and CEA level showed that the expression of AQP1, AQP3, and AQP5 had no effect on the overall survival and disease-free survival. CONCLUSIONS: The current study found a significant correlation between AQP1, AQP3, and AQP5 expression and lymph node metastasis in patients with surgically resected colon cancer.

Notch signaling affects biliary fibrosis via transcriptional regulation of RBP-jκ in an animal model of chronic liver disease.

Liver repair in patients with a chronic liver disease requires the orchestrated action of epithelial, mesenchymal, and inflammatory cells. Notch components are expressed in both the epithelial and mesenchymal compartments of the adult liver and are differentially regulated after injury. However, the functional role of Notch signaling in regulating epithelial/mesenchymal cross-talk during fibrogenic pathologic repair remains unknown. The aim of this study was to investigate how proliferation of the bile duct influences biliary fibrosis and to recognize the effect of inhibiting Notch signaling in biliary fibrotic tissue of the injured liver. We designed a synthetic decoy oligodeoxynucleotide (ODN) for recombination signal binding protein immunoglobulin kappa J (RBP-jκ), which is a common DNA-binding partner of Notch receptors. The effect of blocking RBP-jκ on fibrogenesis was assessed in the 3,5-Diethoxycarbonyl-1,4-dihydrocollidine (DDC) diet mouse model. We observed the reduced fibrosis and decreased expression of associated signaling molecules after the RBP-jκ decoy ODN treatment. These data demonstrate that Notch signaling may play an important role in progression of ductular reaction and fibrosis. Further studies are required to unveil how ductular cells interact with other liver cell types, such as hepatic stellate cells or Kupffer cells,in patients with cholestatic liver diseases based on Notch signaling. These results suggest that controlling the ductular reaction using a synthetic ring type decoy RBP-jκ ODN will help develop a novel therapeutic approach targeting biliary fibrosis in patients with chronic liver diseases.

Congenital primary cutaneous anaplastic large-cell lymphoma: a case report.

Primary cutaneous anaplastic large-cell lymphoma (C-ALCL) is the second most common type of primary cutaneous T-cell lymphoma. The median age of onset of C-ALCL is 60 years. Presented here is a case of congenital CD30-positive (CD30(+)) primary C-ALCL in a 10-day-old neonate who presented with a large erythematous indurative plaque in the right postauricular area. A systemic workup of the patient excluded other potential causes. The neonate was treated with wide excision, but chemotherapy or radiation therapy was not administered, as the patient's parents did not consent to such treatment. The patient has been monitored for 30 months after excision and there has been no disease recurrence. C-ALCL rarely occurs in children, and to the best of our knowledge, this is the first reported case of a neonate with congenital primary C-ALCL.

Two different surgical approaches for prostatic stromal sarcoma: robot-assisted laparoscopic radical prostatectomy and open radical cysto-prostatectomy with ileal conduit.

Stromal sarcoma of the prostate is very rare and shows rapid growth, which consequently is related to poor prognosis. Recently, we treated two cases of prostatic stromal sarcoma: one with robot-assisted laparoscopic radical prostatectomy and the other with open radical cysto-prostatectomy with an ileal conduit. To the best of our knowledge, this is the first case report of a prostatic stromal sarcoma managed by use of a robotic procedure. Here, we report of our experiences in the treatment of prostatic stromal sarcoma by use of two different methods.

Predictive factors and the prognosis of recurrence of colorectal cancer within 2 years after curative resection.

PURPOSE: Because predicting recurrence intervals and patterns would allow for appropriate therapeutic strategies, we evaluated the clinical and pathological characteristics of early and late recurrences of colorectal cancer. METHODS: Patients who developed recurrence after undergoing curative resection for colorectal cancer stage I-III between January 2000 and May 2006 were identified. Early recurrence was defined as recurrence within 2 years after primary surgery of colorectal cancer. Analyses were performed to compare the clinicopathological characteristics and overall survival rate between the early and late recurrence groups. RESULTS: One hundred fifty-eight patients experienced early recurrence and 64 had late recurrence. Multivariate analysis revealed that the postoperative elevation of carbohydrate antigen 19-9 (CA 19-9), venous invasion, and N stage correlated with the recurrence interval. The liver was the most common site of early recurrence (40.5%), whereas late recurrence was more common locally (28.1%), or in the lung (32.8%). The 5-year overall survival rates for early and late recurrence were significantly different (34.7% vs. 78.8%; P < 0.001). Survival rates after the surgical resection of recurrent lesions were not different between the two groups. CONCLUSION: Early recurrence within 2 years after surgery was associated with poor survival outcomes after colorectal cancer recurrence. An elevated postoperative CA 19-9 level, venous invasion, and advanced N stage were found to be significant risk factors for early recurrence of colorectal cancer.

SPOP mutations in prostate cancer across demographically diverse patient cohorts.

BACKGROUND: Recurrent mutations in the Speckle-Type POZ Protein (SPOP) gene occur in up to 15% of prostate cancers. However, the frequency and features of cancers with these mutations across different populations is unknown. OBJECTIVE: To investigate SPOP mutations across diverse cohorts and validate a series of assays employing high-resolution melting (HRM) analysis and Sanger sequencing for mutational analysis of formalin-fixed paraffin-embedded material. DESIGN SETTING AND PARTICIPANTS: 720 prostate cancer samples from six international cohorts spanning Caucasian, African American, and Asian patients, including both prostate-specific antigen-screened and unscreened populations, were screened for their SPOP mutation status. Status of SPOP was correlated to molecular features (ERG rearrangement, PTEN deletion, and CHD1 deletion) as well as clinical and pathologic features. RESULTS AND LIMITATIONS: Overall frequency of SPOP mutations was 8.1% (4.6% to 14.4%), SPOP mutation was inversely associated with ERG rearrangement (P<.01), and SPOP mutant (SPOPmut) cancers had higher rates of CHD1 deletions (P<.01). There were no significant differences in biochemical recurrence in SPOPmut cancers. Limitations of this study include missing mutational data due to sample quality and lack of power to identify a difference in clinical outcomes. CONCLUSION: SPOP is mutated in 4.6% to 14.4% of patients with prostate cancer across different ethnic and demographic backgrounds. There was no significant association between SPOP mutations with ethnicity, clinical, or pathologic parameters. Mutual exclusivity of SPOP mutation with ERG rearrangement as well as a high association with CHD1 deletion reinforces SPOP mutation as defining a distinct molecular subclass of prostate cancer.

The differential expression of TGF-ß1, ILK and wnt signaling inducing epithelial to mesenchymal transition in human renal fibrogenesis: an immunohistochemical study.

Epithelial-to-mesenchymal transition (EMT) is a process for fully differentiated epithelial cells to undergo a phenotypic change to fibroblasts via diverse intracellular signaling pathways. While the pivotal role of fibroblasts in renal fibrosis is widely accepted, their origin remains undefined. In addition, although a large number of studies have provided evidence of EMT in human kidney diseases, specific signaling pathways leading to EMT have not yet been discovered in humans. To evaluate the origin of interstitial fibroblasts and signaling pathways involved in the EMT process, we analyzed the differential expression of EMT-related molecules in paraffin-fixed sections from 19 human fibrotic kidneys and 4 control kidneys. In human fibrotic kidneys, tubular epithelial cells (TECs) with intact tubular basement membrane (TBM) showed loss or down-regulation of an epithelial marker (E-cadherin), de novo expression of mesenchymal markers (vimentin and fibronectin), and significant up-regulation of inducers and mediators controlling the EMT process (transforming growth factor-ß1 (TGF-ß1), p-Smad2/3, ß1-integrin, p38 mitogen-activated protein kinase (MAPK), WNT5B and ß-catenin) in the areas of interstitial inflammation and fibrosis, compared with their expression in control kidneys. In conclusion, the type II EMT process in humans is thought to be an adaptive response of TECs to chronic injury and is regulated by interconnections of TGF-ß/Smad, integrin/integrin-linked kinase (ILK) and wnt/ß-catenin signaling pathways.