OBJECTIVE: To explore the genetic basis for a patient presenting with renal insufficiency. METHODS: The patient was subjected to whole exome sequencing, and the candidate variant was verified by Sanger sequencing. Transcriptional activity of the PAX2 gene was analyzed by using a PRS4-EGFP reporter plasmid. RESULTS: Genetic testing revealed that the patient has carried a novel de novo heterozygous variant c.418C>T (p.Arg140Trp) of the PAX2 gene. The influence of c.389C>G (p.Pro130Arg), c.478G>A (p.Ala160Thr), c.418C>G (p. Arg140Gly) and c.418C>T (p.Arg140Trp) variants on the transcriptional activity was also evaluated. Functional study has illustrated that the PAX2-P130R, PAX2-R140G and PAX2-R140W variants all had a significant inhibitory effect on the transcriptional activity, but not the PAX2-A160T variant. CONCLUSION The isolated renal hypoplasia of the proband is probably due to the likely pathogenic variant of the PAX2 gene.
Coloboma/genetics* ; Genetic Testing ; Humans ; Mutation ; PAX2 Transcription Factor/genetics* ; Renal Insufficiency/genetics* ; Vesico-Ureteral Reflux

OBJECTIVETo investigate the influence of silencing PAX2 gene in vivo on epithelial-mesenchymal transition (EMT) of renal tubular cells in rats with renal interstitial fibrosis.

METHODSA total of 64 Wistar rats were anaesthetized, and unilateral ureteral obstruction (UUO) was performed to establish a rat model of renal interstitial fibrosis. The 64 rats were randomly divided into negative control and PAX2 gene silencing groups (n=32 each). The rats in the control group were transfected with 200 μL NC-siRNA-in vivo jetPEI(TM) solution. Those in the PAX2 gene silencing group were transfected with 200 μL PAX2-siRNA-in vivo jetPEI(TM) solution. Each group was further divided into 4 subgroups based on the post-transfection time (3, 5, 7 and 14 days after transfection), with 8 rats in each subgroup. Renal tissue samples were harvested in each group. Real-time PCR and Western blot were used to measure the mRNA and protein expression of PAX2 in the renal cortex, as well as the mRNA and protein expression of E-cadherin and α-SMA.

RESULTSCompared with the control group, the PAX2 gene silencing group showed significantly lower mRNA and protein expression of PAX2 (P<0.05). In the two groups, the mRNA and protein expression levels of E-cadherin were gradually reduced over the time of obstruction, while those of α-SMA gradually increased. At 14 days after transfection, the PAX2 gene silencing group had significantly higher mRNA and protein expression of E-cadherin but lower mRNA and protein expression of α-SMA compared with the control group (P<0.05).

CONCLUSIONSPAX2 gene silencing can significantly inhibit the process of EMT of renal tubular cells in rats with advanced fibrosis, suggesting that PAX2 gene silencing may have a therapeutic effect on renal interstitial fibrosis.

Animals ; Epithelial-Mesenchymal Transition ; Fibrosis ; Gene Silencing ; Kidney ; pathology ; Male ; PAX2 Transcription Factor ; genetics ; RNA, Messenger ; analysis ; Rats ; Rats, Wistar

OBJECTIVE: To explore the genetic basis of a Chinese pedigree affected with chronic kidney disease (CKD). METHODS: A Chinese pedigree comprised of 10 individuals from four generation who had visited the First Affiliated Hospital of Dali University from August 15, 2018 to July 5, 2021 was selected as the study subject. Clinical data of the proband were collected, and a pedigree survey was conducted. The proband was subjected to whole exome sequencing (WES). Candidate variant was verified by Sanger sequencing and bioinformatic analysis. RESULTS: The proband, a 41-year-old female, has been diagnosed with chronic nephritis for more than 4 years. Routine urinary examination showed proteinuria and blood creatinine of 1 130 μmol/L. Renal biopsy has revealed hyperplastic glomerulonephritis, moderate tubulointerstitial disease and renal arteriosclerosis. Her elder sister, younger brother, younger sister and mother were all diagnosed with CKD stage 5. Except for her elder sister, all of them had deceased, whilst no abnormality was found in the remainders. Genetic testing revealed that the proband and four family members had harbored a c.467G>A missense variant of the PAX2 gene. The variant has been associated with focal segmental glomerulosclerosis and classified as likely pathogenic (PS1+PP3+PP4) based on the guidelines from the American College of Medical Genetics and Genomics (ACMG). CONCLUSION The c.167G＞A variant of the PAX2 gene probably underlay the CKD in this Chinese pedigree.
Adult ; Female ; Humans ; Male ; East Asian People ; Genetic Testing ; Mutation ; PAX2 Transcription Factor/genetics* ; Pedigree ; Renal Insufficiency, Chronic/genetics*

OBJECTIVETo study the effect of L-arginine (L-Arg) on Pax2 expression in the kidneys of pup rats with intrauterine growth retardation (IUGR).

METHODSPregnant rats were randomly assigned into three groups：normal, IUGR and L-Arg treated IUGR. The rats in the normal group were fed with ordinary forage (21% protein) during pregnancy. Those in the other two groups were fed with low diet forage (10% protein) during pregnancy. The L-Arg treated group was given drinking water containing L-Arg (200 mg/kg) daily during 21 days of lactation. Pax2 expression in renal tissues was measured with immunohistochemical staining and Western blot in pup rats of 7 days, 21 days, 2 months and 3 months old.

RESULTSThe immunohistochemical staining showed that Pax2 was not expressed in the pup rats from the normal group at any time point. Pax2 positive cells were found in renal glomerulus and kidney tubules of 2-months- and 3-months-old rats from the IUGR and L-Arg treated groups. And Pax2 expression in 3-months-old rats was significantly higher than that in 2-months-old rats (P<0.05). L-Arg treatment decreased significantly the Pax2 expression in 2-months- and 3-months-old rats when compared with the untreated IUGR group (P<0.05). Western blot showed that Pax2 protein was not expressed in 7-days- and 21-days-old pup rats from three groups. Pax2 protein expression in 2-months- and 3-months-old pup rats from the IUGR and L-Arg treated groups increased significantly compared with normal controls. Pax2 protein expression in the pup rats from the L-Arg treated group was significantly lower than that in the untreated IUGR pup rats (P<0.01).

CONCLUSIONSPax2 is expressed in the kidneys of IUGR rats during adulthood. L-Arg treatment can decrease the expression of Pax2.

Animals ; Arginine ; pharmacology ; Blotting, Western ; Female ; Fetal Growth Retardation ; metabolism ; Immunohistochemistry ; Kidney ; chemistry ; Male ; PAX2 Transcription Factor ; analysis ; Rats ; Rats, Sprague-Dawley

OBJECTIVE: To investigate the difference of Pax2 and P53 expressions in children with primary nephritic syndrome (PNS) and the effect of Pax2 on glucocorsteroid (GC)-resistance. METHODS: Renal Pax2 and P53 expressions in children with PNS (40 patients) were detected by immunohistochemistry. A semiquantitative score was used to evaluate the injury degree of the glomeruli and the tubulointerstitium, and correlation analysis was done among Pax2, P53 and pathologic score. RESULTS: Pax2 and P53 expressions were not found in the control group. Pax2 expression of renal tubule epithelia exsisted in children with PNS and there was weak or no expression of Pax2 in the podocytes. Pax2 expressions in the proximal tubule and the distal tubule in the GC-resistant group were more intense than those in the GC-intensive group (P <0.01). The more the Pax2 expression in the tubule, the more abnormal structure such as dilation and atrophy. Pax2 expression in the tubule epithelia was positively correlated with pathologic score of tubulointerstitium (P < 0.01). There was no P53 expression in the GC-intensive group, but there exsisted P53 expression in parts of the patients from the GC-resistant group, mainly distributing in the renal tubular epithelia. P53 expression was positively correlated with P53 expression and the pathologic score of tubulointerstitium (P < 0.01). CONCLUSION Over-expression of Pax2 in the renal tubule epithelia may improve P53 expression to a certain degree, which may aggravate the lesion of the renal tubule. It may be one of the mechanisms resulting in GC-resistant in children with PNS.
Adolescent ; Child ; Child, Preschool ; Drug Resistance ; Female ; Glucocorticoids ; therapeutic use ; Humans ; Male ; Nephrotic Syndrome ; drug therapy ; metabolism ; PAX2 Transcription Factor ; biosynthesis ; genetics ; Tumor Suppressor Protein p53 ; biosynthesis ; genetics

OBJECTIVETo study the expression of carbonic anhydrase IX (CAIX), PAX2 and PAX8 in different types of renal epithelial tumor and their association with clinicopathologic characteristics.

METHODSImmunohistochemical study by EnVision method was performed in order to assess the expression of CAIX, PAX2 and PAX8 in 155 cases of renal cell carcinoma and 4 cases of metastatic clear cell renal cell carcinoma (CCRCC). Ninety-six cases of non-neoplastic renal parenchymal tissue adjacent to CCRCC, 8 cases of clear cell hepatocellular carcinoma and 2 cases of clear cell hidradenoma were used as controls.

RESULTSCAIX was commonly expressed in CCRCC (94.0%, 63/67), of which 77.8% (49/63) showed strong positivity. CAIX was focally positive in papillary renal cell carcinoma, collecting duct carcinoma and urothelial carcinoma of renal pelvis. It was negative in chromophobe renal cell carcinoma, oncocytoma and adjacent non-neoplastic renal tissue. CAIX was also strongly expressed in the 4 cases of metastatic CCRCC. Focal expression of CAIX was demonstrated in the 8 cases of clear cell hepatocellular carcinoma and 2 cases of clear cell hidradenoma. The expression of CAIX in CCRCC did not correlate with tumor grading, clinical staging and presence of distal metastasis. On the other hand, PAX2 showed positive expression in different types of renal epithelial tumor, clear cell hepatocellular carcinoma and clear cell hidradenoma in various degrees. In contrast, PAX8 was commonly expressed in all types of renal epithelial tumor, with the exception of urothelial carcinoma of renal pelvis. PAX8 was not expressed in clear cell hepatocellular carcinoma and clear cell hidradenoma. Regarding diagnosis of CCRCC, CAIX demonstrated high sensitivity and specificity. PAX2 showed high specificity but low sensitivity. PAX8 was sensitive and specific in the diagnosis of renal epithelial tumor.

CONCLUSIONSCAIX is a useful immunohistochemical marker with high specificity and sensitivity in distinguishing CCRCC from other types of renal epithelial tumor and clear cell tumors of non-renal origin. PAX2 is a marker with high sensitivity and low specificity for diagnosis of renal epithelial tumors. PAX8 is typically expressed in renal epithelial tumors. The combined detection of CAIX, PAX2 and PAX8 is useful in the diagnosis and differential diagnosis of renal epithelial tumors.

Adenoma, Oxyphilic ; metabolism ; pathology ; Antigens, Neoplasm ; metabolism ; Carbonic Anhydrase IX ; Carbonic Anhydrases ; metabolism ; Carcinoma, Renal Cell ; metabolism ; pathology ; Diagnosis, Differential ; Humans ; Kidney Neoplasms ; metabolism ; pathology ; Male ; PAX2 Transcription Factor ; metabolism ; PAX8 Transcription Factor ; Paired Box Transcription Factors ; metabolism

OBJECTIVETo evaluate the two-tier system for the grading of ovarian serous carcinomas, and to analyze Pax2, p53, Ki-67 protein expression and their prognostic values for low- and high-grade ovarian serous carcinomas.

METHODSA total of 38 cases of low-grade and 100 cases of high-grade ovarian serous carcinomas were selected based on the two-tier grading system. Immunohistochemistry was used to detect Pax2, p53 and Ki-67 protein expression in all cases. Correlation of the two-tier system with immunohistochemical results and prognostic parameters were performed.

RESULTS(1) The overall survival, disease-free survival and 5-year survival rates were significantly higher in the low-grade serous carcinoma cases than in the high-grade cases (P < 0.05). (2) Significant differences in protein expressions were found between the low- and high-grade serous carcinomas. The high-grade serous carcinomas had a significantly higher expression level of p53 (55.0% vs 13.2%, P < 0.05) and Ki-67 (42.1% vs 13.7%, P < 0.05), while low-grade carcinomas had a significantly higher expression level of Pax2 (65.8% vs 13.0%, P < 0.05). (3) Pax2 positive cases had a significantly better overall survival and 5-year survival rates than Pax2 negative cases (P < 0.05). The expressions of p53 and Ki-67 were found to have little correlation with overall survival and disease-free survival (P > 0.05).

CONCLUSIONSThe two-tier system for the grading of ovarian serous carcinomas has a good prognostic value. There are significantly differences in expressions of Pax2, p53 and Ki-67 between low- and high-grade ovarian serous carcinomas. Compared with p53 and Ki-67, Pax2 is likely a better prognostic indicator for ovarian serous carcinoma.

CA-125 Antigen ; metabolism ; Cystadenocarcinoma, Serous ; classification ; metabolism ; mortality ; pathology ; Disease-Free Survival ; Female ; Follow-Up Studies ; Humans ; Immunohistochemistry ; Ki-67 Antigen ; metabolism ; Membrane Proteins ; metabolism ; Middle Aged ; Neoplasm Grading ; Neoplasm Staging ; Ovarian Neoplasms ; classification ; metabolism ; mortality ; pathology ; Ovary ; pathology ; PAX2 Transcription Factor ; metabolism ; Survival Rate ; Tumor Suppressor Protein p53 ; metabolism

BACKGROUNDBiomarkers in breast neoplasms provide invaluable information regarding prognosis and help determining the optimal treatment. We have examined the possible correlation between cancer stem cell (CSC)-like markers (CD133, paired box gene 2 protein (PAX2), epithelial specific antigen (ESA)), and a new membrane estrogen receptor (G-protein coupled receptor 30 (GPR30)) in invasive ductal breast carcinomas with known clinicopathological parameters, tumor recurrence, and expression of some known biomarkers.

METHODSIn 74 invasive ductal breast carcinomas, we investigated the protein expression of these molecular markers by immunohistochemistry, and their associations with known clinicopathological parameters, tumor recurrence, and expression of some known biomarkers. We studied the interrelationship between the expressions of these proteins.

RESULTSCD133, a putative CSC marker, was positively related to tumor size, tumor stage, and lymph node metastasis. PAX2 was negatively correlated with tumor recurrence. ESA, one of the breast CSC markers, was an indicator of tumor recurrence. GPR30 was associated with hormone receptors. Despite the correlation between GPR30 and the nuclear estrogen receptor, the expression was dependent. Positive staining of GPR30 in tumors displayed a significant association with high C-erbB2 expression and a tendency for tumor recurrence. A positive relationship between GPR30 and CD133 existed.

CONCLUSIONDetecting the expression of CD133, PAX2, ESA, and GPR30 in invasive ductal breast carcinomas may be of help in more accurately predicting the aggressive properties of breast cancer and determining the optimal treatment.

AC133 Antigen ; Adult ; Aged ; Antigens, CD ; analysis ; Biomarkers, Tumor ; analysis ; Breast Neoplasms ; chemistry ; pathology ; Carcinoma, Ductal, Breast ; Female ; Glycoproteins ; analysis ; Humans ; Immunohistochemistry ; Membrane Proteins ; analysis ; Middle Aged ; Neoplasm Invasiveness ; Neoplastic Stem Cells ; chemistry ; PAX2 Transcription Factor ; analysis ; Peptides ; analysis ; Receptors, Estrogen ; analysis ; Receptors, G-Protein-Coupled ; analysis ; Receptors, Progesterone ; analysis

The development of human endometrial carcinoma (HEC) is a complex pathologic process involves several oncogenes and tumor suppressor genes. The full-length paired-box gene 2 (pax2), a recently discovered oncogene, promotes cell proliferation and growth and inhibits apoptosis of HEC cells. Here, we examined the effect of pax2 small interfering RNA (siRNA) on the growth of transplanted HEC cells in nude mice. The expression of Pax2 in 21 cases of normal endometrium and 38 cases of HEC was examined by immohistochemistry (IHC). HEC models were developed by subcutaneously transferring HEC cells into nude mice, followed by treatment with empty lentivirus vector, lentivirus vector-based pax2 siRNA, and phosphate buffered saline, respectively. Four weeks later, tumor size was measured, tumor inhibition rate was calculated, and histological analyses were conducted after staining with hematoxylin and eosin. The expression of Pax2 and Bcl-2 was detected by Western blot; proliferating cell nuclear antigen (PCNA) was detected by IHC. Significant differences were observed in the positive rate of Pax2 between normal endometrium and HEC (14.2% vs. 60.5%, P < 0.01). The expression index of Pax2 in well differentiated tumors was 1.88 ± 1.68, much lower than that in tumors of moderate (3.07 ± 1.96, P < 0.05) or poor differentiation (5.45 ± 2.76, P <0.01). Tumor necrosis increased, nuclear basophilia stain decreased, tumor growth was inhibited, and PCNA, Pax2, and Bcl-2 expression was reduced in HEC models treated with pax2 siRNA. These results indicate that Pax2 expression is related to HEC tumor biology with the increased expression of Pax2 correlated to malignancy. pax2 siRNA down-regulates Pax2 expression and inhibits tumorigenesis of HEC in nude mice, possibly due to cell apoptosis and the inhibition of tumor proliferation induced by down-regulation of Bcl-2.
Adult ; Aged ; Animals ; Apoptosis ; Cell Line, Tumor ; Cell Proliferation ; Down-Regulation ; Endometrial Neoplasms ; metabolism ; pathology ; Female ; Genetic Vectors ; Humans ; Lentivirus ; genetics ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Middle Aged ; Neoplasm Transplantation ; PAX2 Transcription Factor ; genetics ; metabolism ; Proliferating Cell Nuclear Antigen ; metabolism ; Proto-Oncogene Proteins c-bcl-2 ; metabolism ; RNA Interference ; RNA, Small Interfering ; genetics ; Transfection ; Tumor Burden

OBJECTIVETo study the clinical and histopathologic features of metanephric adenoma (MA).

METHODSEight cases of recently diagnosed MA were retrieved from archival file. Immunohistochemical study was carried out. The clinical characteristics, pathologic parameters, differential diagnosis, treatment options and prognosis of MA were analyzed, with literature review.

RESULTSThe patients included 6 females and 2 males. The age of patients ranged from 12 to 70 years (mean=43.6 years). Eight cases were located in renal cortex and showed well-defined borders. Histologically, the tumor was composed of tubules lined by small basophilic cells and embedded in an edematous stroma. Papillary structures and psammoma bodies were focally seen. Immunohistochemical study showed that the tumor cells were positive for PAX2 and vimentin in all the 8 cases. WT-1 was positive in 2 cases, focal and weak in 5 cases, and negative in 1 case. CK-Pan was positive in 3 cases. CK7 staining was mostly negative, with focal and weak positivity only in 1 case. The proliferative index, as highlighted by Ki-67 staining, was less than 2% in 7 cases and focally around 5% in 1 case. The expressions of CK20, CD10, RCC, epithelial membrane antigen, CD56, synaptophysin and chromogranin A were negative. Follow-up information from 7 to 57 months was available in all patients; and none of them developed local recurrence or distant metastasis.

CONCLUSIONSThe diagnosis of MA relies primarily on thorough histologic examination and immunohistochemical study (vimentin and PAX2 positive, WT-1 focally and weakly positive in some cases, and low proliferative index). Correlation with clinical and radiologic findings would also be helpful.

Adenoma ; diagnostic imaging ; metabolism ; pathology ; surgery ; Adolescent ; Adult ; Aged ; Biomarkers, Tumor ; metabolism ; Carcinoma, Renal Cell ; metabolism ; pathology ; Child ; Diagnosis, Differential ; Female ; Follow-Up Studies ; Humans ; Kidney Neoplasms ; diagnostic imaging ; metabolism ; pathology ; surgery ; Male ; Middle Aged ; Nephrectomy ; methods ; PAX2 Transcription Factor ; metabolism ; Tomography, X-Ray Computed ; Vimentin ; metabolism ; WT1 Proteins ; metabolism ; Wilms Tumor ; pathology ; Young Adult