Glomerular nestin expression: possible predictor of outcome of focal segmental glomerulosclerosis in children.

BACKGROUND: A high prevalence of chronic kidney disease among children with focal segmental glomerulosclerosis (FSGS) leads to a permanent quest for good predictors of kidney dysfunction. Thus, we carried out a retrospective cohort study in order to examine known clinical and morphological predictors of adverse outcome, as well as to investigate glomerular nestin expression as a potential new early predictor of kidney dysfunction in children with FSGS. Relationships between nestin expression and clinical and morphological findings were also investigated. METHODS: Among 649 renal biopsy samples, obtained from two children's hospitals, FSGS was diagnosed in 60 children. Thirty-eight patients, who met the criteria for this study, were followed up for 9.0 ± 5.2 years. Using Kaplan-Meier and Cox's regression analysis, potential clinical and morphological predictors were applied in two models of prediction: after disease onset and after the biopsy. RESULTS: The present study revealed the following significant predictors of kidney dysfunction: patients' ages at disease onset, as well as age at biopsy, resistance to corticosteroid treatment, serum creatinine level, urine protein/creatinine ratio, vascular involvement, tubular atrophy, interstitial fibrosis, and decreased glomerular nestin expression. CONCLUSIONS: The most important finding of our study is that nestin can be used as a potential new early morphological predictor of kidney dysfunction in childhood onset of FSGS, since nestin has been obviously decreased in both sclerotic and normal glomeruli seen by light microscopy.

Variable Expression of Neural Cell Adhesion Molecule Isoforms in Renal Tissue: Possible Role in Incipient Renal Fibrosis.

Rare neural cell adhesion molecule (NCAM) positive cells have been previously described within the normal human adult kidney interstitium, speculating that they could increase in the interstitium with incipient interstitial renal fibrosis (IRF). In the present study, among 93 biopsy samples of various kidney diseases, NCAM+ interstitial cells were detected in 62.4% cases. An increased number of NCAM+ cells was significantly observed only in incipient IRF compared to normal renal tissues and advanced IRF stages (p<0.001), independently of underlying diseases (p = 0.657). All three major NCAM isoforms' RT-PCR bands were visible either in normal or in kidneys with incipient IRF, albeit their mRNA expression levels measured by qRT-PCR were different. Applying qRT-PCR on pure NCAM+ cells population, obtained by laser capture microdissection, significant mRNA over-expression of NCAM140kD isoform was found in NCAM+ cells within incipient IRF (p = 0.004), while NCAM120kD and NCAM180kD isoforms were not changed significantly (p = 0.750; p = 0.704; respectively). Simultaneously, qRT-PCR also showed significant αSMA (p = 0.014) and SLUG (p = 0.004) mRNAs up-regulation within the NCAM+ cells of incipient IRF, as well as highly decreased matrix metalloproteinases (MMP) -2 and -9 mRNAs (p = 0.028; p = 0.036; respectively). However, using double immunofluorescence MMP-9 could still be detectable on the protein level in rare NCAM+ cells within the incipient IRF. Further characterization of NCAM+ cells by double immunofluorescent labeling revealed their association with molecules involved in fibrosis. Fibroblast growth factor receptor 1 (FGFR1) and α5ß1 integrin were extensively expressed on NCAM+ cells within the incipient IRF areas, whereas human epididymis protein-4 (HE4) was found to be present in few NCAM+ cells of both normal and interstitium with incipient fibrosis. Heterogeneity of NCAM+ interstitial cells in normal and incipient IRF, concerning molecules related to fibrosis and variable expression of NCAM isoforms, could suggest diverse role of NCAM+ cells in homeostasis and in regulation of renal fibrosis in diseased kidneys.

NCAM and FGFR1 coexpression and colocalization in renal tumors.

Neural cell adhesion molecule (NCAM) and fibroblast growth factor receptor (FGFR) have a role in epithelial-mesenchymal transformation during tumor genesis. Interplay between both molecules activates FGFR signaling and it could be responsible for tumor development. Renal epithelial tumors were analyzed for FGFR1 and NCAM coexpression by immunohistochemistry and for colocalization of these molecules on the particular tumor cells by triple immunofluorescence. Detection of NCAM isoforms in renal tumors was evaluated by RT-PCR. Applying immunohistochemistry we revealed that the majority of analyzed renal neoplasms, including renal cell carcinoma (RCC) and oncocytoma coexpressed NCAM and FGFR1. Triple immunofluorescent technique confirmed that both markers are commonly colocalized on the same tumor cells. Interestingly, it seemed that different position of NCAM and FGFR1 expression on renal tumor cells is related to renal tumor type or grade: exclusively membranous FGFR1/NCAM expression occurred in low grade clear cell RCC (cRCC); cytoplasmatic and membranous expression was present in high grade cRCC and other RCC types; oncocytoma showed only cytoplasmatic staining of both markers. NCAM-140 and NCAM-120 were detected in almost all analyzed renal neoplasms. Expression of both molecules on different cell compartments in various kidney tumors indicated that NCAM/FGFR1 interaction could play distinct roles in renal tumor genesis.

Rapidly progressive course of primary renal synovial sarcoma--case report.

INTRODUCTION: Primary kidney sarcoma, especially synovial sarcoma (SS), is a very rare neoplasm. Preoperative signs and symptoms are very similar to renal cell carcinoma, therefore, the proper diagnosis is very difficult and usually made after nephrectomy.This is a case report of primary renal SS. CASE OUTLINE: A 38-year-old man presented with a history of fever and hematuria, and right flank pain 3 weeks ago. Abdominal computerized tomography revealed a heterogeneous well-marginated soft tissue mass arising in the lower part of the right kidney. Right nephrectomy was performed. A cystic tumor of 120 x 85 mm in size with soft solid growth, and with the extensive areas of hemorrhage and necrosis was seen on gross examination. Histopathology revealed a neoplasm composed of solid monomorphic sheets of spindle cells. Immunohistochemistry showed tumor cells strongly positive for BCL2, CD99, CD56 and vimentin, and focally positive for epithelial membrane antigen (EMA). The histological diagnosis of primary renal SS was based on morphology and immunohistochemistry. FISH analysis and RT-PCR was carried out on formalin-fixed paraffin-embedded tissue sections. The molecular analysis demonstrated translocation of SYT gene on chromosome 18 and SSX2 gene on chromosome X. The findings were consistent with diagnosis of SS. CONCLUSION: Our case shows that histopathological diagnosis of primary kidney SS, although difficult, is possible to be made on the basis of morphological and immunohistochemical analysis. However, this diagnosis should be corroborated by molecular techniques confirming SYT-SSX translocation on chromosome 18 and chromosome X. Here we present visceral monophasic SS with aggressive clinical course and poor outcome.

[Small cell neuroendocrine carcinoma of the urinary bladder].

Among neuroendocrine tumors of the urinary bladder, small cell carcinoma (SCCB) is the most common one. Less frequent is carcinoid tumour and very rare is a large-cell neuroendocrine carcinoma. Small cell neuroendocrine carcinoma is a very aggressive tumour, with major frequency in the seventh decade. In 95% of patients it presents with hematuria and muscle invasive disease. A case of a patient with the urinary bladder tumour, which had muscle invasion and extension in perivesical tissue, was presented. The patient was diagnosed with combined form of the tumour, consisting of small cell and squamous cell patterns. Some of the imunochistochemical markers used in diagnosis were chromogranin A, synaptophysin, cytokeratins, LCA and Ki-67. Consequently, neuroendocrine differentiation of small cell patterns of the tumour was proven. Neoadjuvant cisplatin- based chemotherapy followed by radical resection should be considered as the treatment of choice in surgically resectabile SCCB. Because of that it is essential to make histopathologic diagnosis of SCCB in transuretral tumour samples using, chromogranin A or synapthysin.

Expression of neural cell adhesion molecule in renal cell carcinoma.

Neural cell adhesion molecule (NCAM) is important for cell migration and it could be expressed in some renal cell carcinoma (RCC). In recent decades, the incidence of RCC has been steadily rising by 2-4% each year. In this study NCAM expression and correlation with nuclear grade in different RCC were analyzed. We analyzed NCAM expression on 7 different RCC cell lines and 32 different RCC by immunohistochemistry, immunofluorescence, Western blot and FACS analysis. NCAM expression is detected in 6 cell lines and 16 RCC cases. NCAM-140 kDa isoform is expressed in different RCC and RCC cell lines. NCAM expression in non-invasive clear cell RCC is lower than in clear cell RCC with high nuclear grade. Expression of NCAM is not exclusive for specific RCC type, so NCAM can not be used as a specific diagnostic marker for RCC. NCAM expression is in correlation with nuclear grade in clear cell RCC, suggesting that NCAM expression is involved in aggressive behavior and metastatic potential in RCC.

[Pax-2 antigen expression in kidney tumours].

UNLABELLED: Pax-2 transcriptional factor is expressed during kidney development and could re-express in renal tumors. The aim of this study was to examine Pax-2 expression in different types of renal cell carcinoma (RCC) in order to see whether it is good immunohistochemical marker. METHOD: We analyzed 48 different renal tumours stained with Pax-2 antibody. Pax-2 positive reaction was noticed in nucleus or cytoplasm. Expression of this antigen in tumours tissue was correlated with tumour stage and nuc-lear grade. Pax-2 expression between different histological RCC types was analyzed by chi2 test and Fishers test for two in-depended samples. RESULTS: Pax-2 is expressed by a high percentage of re-nal tumors regardless of histologic type. Significant diffe-rence of Pax-2 expression between oncocytomas and chromofobe RCC was found. CONCLUSION: Nuclear expression of Pax-2 is useful diagnostic kidney tumour marker. Pax-2 showed stronger expression in lower malignancy kidney tumours and in oncocytomas, than in high grade RCC like in those with sarcomatoid differentiation