Glycosaminoglycans (GAGs) are heterogeneous, linear, highly charged, anionic polysaccharides consisting of repeating disaccharides units. GAGs have some biological significance in cancer progression ...(invasion and metastasis) and cell signaling. In different cancer types, GAGs undergo specific structural changes. In the present study, in depth investigation of changes in sulfation pattern and composition of GAGs, heparan sulfate (HS)/heparin (HP), chondroitin sulfate (CS)/dermatan sulfate and hyaluronan (HA) in normal renal tissue (NRT) and renal cell carcinoma tissue (RCCT) were evaluated. The statistical evaluation showed that alteration of the HS (HS
NRT
= 415.1 ± 115.3; HS
RCCT
= 277.5 ± 134.3), and CS (CS
NRT
= 35.3 ± 12.3; CS
RCCT
= 166.7 ± 108.8) amounts (in ng/mg dry tissue
)
were statistically significant (
p
< 0.05). Sulfation pattern in NRT and RCCT was evaluated to reveal disaccharide profiles. Statistical analyses showed that RCCT samples contain significantly increased amounts (in units of ng/mg dry tissue
)
of 4S
CS
(NRT = 25.7 ± 9.4; RCCT = 117.1 ± 73.9), SE
CS
(NRT = 0.7 ± 0.3; RCCT = 4.7 ± 4.5), 6S
CS
(NRT = 6.1 ± 2.7; RCCT = 39.4 ± 34.7) and significantly decreased amounts (in units of ng/mg dry tissue
)
of NS6S
HS
(RCCT = 28.6 ± 6.5, RCCT = 10.2 ± 8.0), NS2S
HS
(RCCT = 44.2 ± 13.8; RCCT = 27.2 ± 15.0), NS
HS
(NRT = 68.4 ± 15.8; RCCT = 50.4 ± 21.2), 2S6S
HS
(NRT = 1.0 ± 0.4; RCCT = 0.4 ± 0.3), and 6S
HS
(NRT = 60.6 ± 17.5; RCCT = 24.9 ± 12.3). If these changes in GAGs are proven to be specific and sensitive, they may serve as potential biomarkers in RCC. Our findings are likely to help us to show the direction for further investigations to be able to bring different diagnostic and prognostic approaches in renal tumors.
Glomerulopathy with fibronectin deposits is a rare hereditary kidney disease characterized by the extensive deposition of fibronectin in glomeruli, particularly in mesangial regions and ...subendothelial zones. Prognostically, the disease is known as slowly progressive, leading to kidney failure in most cases. We recently diagnosed glomerulopathy with fibronectin deposits in a 24-year-old man in whom proteinuria was detected incidentally. Genetic analysis of the fibronectin 1 ( FN1 ) gene showed heterozygosity for the Y973C mutation. The same mutation was found in his elder brother, who similarly experienced proteinuria. Both patients had normal kidney function but persistent proteinuria after 30 months and 11 years of follow-up, respectively.
TERT promoter mutations (TERT-mut) are detectable in the majority of urothelial carcinomas. The detection of TERT-mut in urine is under investigation as a potential urine-based molecular-screening ...assay for bladder cancer. A small but significant number of bladder carcinomas are pure squamous cell carcinoma. We sought to assess the incidence of TERT-mut in squamous cell carcinoma of the urinary bladder. A retrospective search of the institutional pathology archives yielded 15 cystectomy specimens performed for squamous cell carcinoma (2000-2014). Histologic slides were reviewed by a senior urologic pathologist to confirm the diagnosis and select a representative formalin-fixed paraffin-embedded tissue block for mutational analysis. All cases yielded adequate material for DNA analysis. Sequencing for TERT-mut was performed using previously described SafeSeq technique. We detected TERT-mut in 12/15 (80%) of bladder squamous cell carcinomas. TERT promoter mutations, commonly found in conventional urothelial carcinoma, are also highly prevalent in urinary bladder squamous cell carcinoma suggesting a common tumorigenesis and potential utility as a molecular urine-based-screening assay.
Introduction
The dissection of perirenal fat is of critical importance to kidney surgery and ease of dissection is more important when using minimally invasive approaches. This study aimed to ...determine the clinical, radiological, and pathological significance of adherent perirenal fat (APF).
Materials and Methods
This prospective study included 22 patients scheduled for partial nephrectomy and 40 patients for donor nephrectomy. Intraoperative fat dissection time was recorded, and the complexity of perirenal fat dissection was surgeon‐classified as easy, moderate, and difficult. Perirenal fat and subcutaneous fat thickness were measured. Measurement of perirenal fat depth and the Hounsfield unit (HU) for both perirenal and subcutaneous fields were performed using computed tomography (CT) images. All specimens were submitted for histopatological analysis. Researchers in each arm were blinded to other researchers' data.
Results
Mean age of the patients was 51.3 ± 12.7 years. Mean perirenal fat dissection time was 15.0 ± 13.5 minutes. Patient demographics, BMI, nor occupational status differed between the 3 complexity of perirenal fat dissection groups. Radiological findings showed that there was a significant correlation between perirenal fat depth and complexity of perirenal fat dissection (P < .05), but not with HU measurements or subcutaneous fat thickness. Surgeon classification of the complexity of perirenal fat dissection was in accordance with the duration of dissection (P < .05). Perinephric fat contained more fibrous tissue in the patients with histologically proven APF than in those without (P < .05).
Conclusions
APF is a challenge during kidney surgery. Difficult dissection prolongs the duration of perirenal fat dissection and surgery. Perirenal fat thickness measured via preoperative CT might be used to predict APF.
Somatic activating mutations in the promoter of the
telomerase reverse transcriptase (TERT)
gene are the most common genetic alterations in urothelial carcinoma (UC) of the bladder and upper urinary ...tract. Little is known, however, about
TERT-
mutation status in the relatively uncommon but clinically aggressive micropapillary (MPC) variant. We evaluated the presence of
TERT
promoter mutations in MPC of the bladder and upper urinary tract. A retrospective search of our archives for MPC and UC with micropapillary features (2005–2014) was performed. All slides were reviewed to confirm the histologic diagnosis. Thirty-three specimens from 31 patients had FFPE blocks available for DNA analysis and were included in the study. Intratumoral areas of non-micropapillary histology were also evaluated when present. Samples were analyzed with Safe-SeqS, a sequencing error reduction technology, and sequenced using the Illumina MiSeq platform.
TERT
promoter mutations were detected in all specimens with pure MPC (18 of 18) and UC with focal micropapillary features (15 of 15)
.
Similar to conventional UC, the predominant mutations identified occurred at positions −124 (C228T) (85 %) and −146 (C250T) (12 %) bp upstream of the
TERT
ATG start site. In heterogeneous tumors with focal variant histology, intratumoral concordant mutations were found in variant (MPC and non-MPC) and corresponding conventional UC. We found
TERT
promoter mutations, commonly found in conventional UC, to be frequently present in MPC. Our finding of concordant intratumoral mutational alterations in cases with focal variant histology lends support to the common oncogenesis origin of UC and its variant histology.
Background
We aimed to investigate the immuno-histochemical expression of C4d, ADAM10 and WT1 in kidney biopsies of immunoglobulin A nephropathy (IgAN) patients and correlate the findings with ...clinical, laboratory and histopathologic features in the hope of defining new parameters to better understand the pathogenesis of the disease, and predict prognosis.
Materials and methods
Paraffin-embedded kidney biopsy samples of 128 IgAN patients were immuno-histochemically treated with C4d and ADAM10/WT1 dual stain. Results were evaluated according to Oxford classification parameters, epidemiologic features, laboratory findings at presentation and clinical follow-up.
Results
We observed C4d positivity in 40.6% of our patients, 25% of which was mesangial/peri-mesangial (m/pm) staining. Only m/pmC4d positivity statistically correlated with progression to end-stage renal disease (ESRD). M/pmC4d positive patients had statistically significantly higher baseline proteinuria levels, presence of crescents and > 25% segmental sclerosis of glomeruli. There was cytoplasmic staining of WT1 in 11.2% of cases. Presence of cWT1 correlated with m/pmC4d positivity and progression to ESRD. There was no glomerular ADAM10 detected and tubular expression of this protein did not relate to amount of tubular damage or other parameters.
Conclusion
This study is the first to show that cWT1is involved in IgAN and appears as an independent variable for worse prognosis.
To investigate if remote ischemic preconditioning (RIPC) can offer any renoprotective value by counteracting the deleterious effect of partial nephrectomy (PN) under warm ischemia on renal function.
...Four groups, each with 5 Wistar albino rats, were constructed; RIPC + PN, PN, RIPC and sham. Right nephrectomy was performed to constitute a solitary kidney model. RIPC denoted sequential clamping/declamping of the femoral artery/vein complex. PN was performed under warm-ischemia following RIPC. Blood samples were collected on multiple occasions until euthanasia on day 7. Immunoassays were conducted to measure the serum and tissues levels of kidney injury markers. Kidneys were examined histologically and morphometric analyzes were performed using digital scanning.
IL-33 levels did not differ significantly between the groups. Serum levels of KIM-1, NGAL, and aldose reductase in RIPC + PN, PN and RIPC groups were significantly lower than that of sham group. Tissue biomarker levels were similar across groups. The observed trend in mean necrosis area of PN group was higher than that of RIPC + PN group (p > 0.05). The transitional zone between necrosis and healthy tissue showed a trend towards increasing width in the rats subjected to RIPC before PN vs. those who underwent PN without RIPC (p > 0.05).
RIPC failed to counteract the renal functional consequences of PN under warm ischemia in a solitary kidney animal model. The supportive but marginal histological findings in favor of RIPC's renoprotective potential were not supplemented with the changes in serum and tissue biomarker levels.
Summary TERT promoter mutations ( TERT-mut ) have been detected in 60–80% of urothelial carcinomas. A molecular urine-based screening assay for the detection of TERT-mut is currently being pursued by ...our group and others. A small but significant number of bladder carcinomas are adenocarcinoma (ACA). The current study assesses the incidence of TERT-mut in primary adenocarcinomas of urinary bladder. A retrospective search of our institutional pathology records identified 23 cystectomy specimens with a diagnosis of ACA (2000–2014). All slides were reviewed by a senior urologic pathologist to confirm tumor type and select a representative formalin-fixed paraffin embedded (FFPE) block for mutational analysis. Adequate material for DNA testing was available in 14 cases 7 enteric type and 7 not otherwise specified (NOS). TERT-mut sequencing analysis was performed using previously described SafeSeq technique. Overall, 28.5% of primary adenocarcinoma harbored TERT-mut . Interestingly 57% of non-enteric adenocarcinoma were mutation positive, while none of the enteric-type tumors harbored mutations. Similar to urothelial carcinoma, we found a relatively higher rate of TERT-mut among non-enteric type adenocarcinoma further supporting the potential utility of TERT-mut urine-based screening assay for bladder cancer.
PDF
