MYH9-related disorder with sole presentation of end-stage kidney disease and long-term, recurrence-free living after living donor renal transplantation: a case report.

MYH9-related disorders are a group of autosomal dominant disorders caused by mutations in MYH9, and are characterized by thrombocytopenia, sensorineural hearing loss, cataracts, and renal failure. Here, we report a case of chronic renal failure due to MYH9-related disorder with renal symptoms in a patient who underwent living-donor renal transplantation. The patient was diagnosed with proteinuria during a health checkup at the age of 12 years. Her renal function gradually deteriorated, and hemodialysis was initiated at 34 years of age. No definitive diagnosis of renal disease was made through renal biopsy. At the age of 35, she underwent living-donor renal transplantation from her mother as the donor. Six years after transplantation, her renal function remained stable, and no evidence of recurrent nephritis was found during renal biopsies. The family history revealed that her father, uncle, and younger brother had end-stage kidney disease. Genetic testing revealed a mutation (p.E1653D) related to the MYH9 gene. As her father had a history of renal biopsy and was diagnosed with focal segmental glomerulosclerosis (FSGS), we diagnosed chronic renal failure due to FSGS associated with MYH9 disorder. There were no findings suggestive of hearing loss, cataracts, or thrombocytopenia in the recipient or their family members with renal failure, and no symptoms other than renal failure were noted.

Assessment of Tumor Markers in Renal Transplant Recipients.

Background/Aim: Malignant tumors are diagnosed using various methods, including diagnostic imaging methods. The measurement of tumor markers is commonly used because of its noninvasiveness and convenience. Furthermore, it is known that the excretion and metabolism of some tumor markers are affected by impaired renal function. In the present study, we investigated the effect of improved renal function on pre-and post-transplantation changes in tumor marker levels [carcinoembryonic antigen (CEA), alpha-fetoprotein (AFP), carbohydrate antigen 19-9 (CA19-9), and prostate-specific antigen (PSA)] in renal transplant recipients. Patients and Methods: A total of 116 renal transplant recipients, who had not been diagnosed with malignancies between January 2012 and December 2019, were included, and tumor markers were investigated. Results: CEA showed a significant decrease after kidney transplantation, regardless of the dialysis type (3.6→2.6 ng/ml, p<0.001), while other tumor markers showed a significant increase (AFP: 3.6→3.7 ng/ml; CA19-9: 16.2→19.5 U/ml; PSA: 0.95→1.05 ng/ml; all p<0.05). Pre- and postoperative eGFR ratios and postoperative liver function were identified as factors influencing the postoperative CEA and CA19-9 values, while PSA was influenced by the duration of dialysis. No statistically significant factors were found for AFP levels. Conclusion: Caution should be exercised when investigating tumor markers in patients with renal dysfunction, as tumor marker levels may vary depending on the pathophysiology of each patient.

Fat Necrosis Mimicking Local Recurrence With Fluorodeoxyglucose Positron Emission Tomography (FDG-PET) Positivity After Partial Nephrectomy for Renal Cell Carcinoma.

We report a case of fat necrosis with positive results on fluorodeoxyglucose positron emission tomography (FDG-PET)-CT imaging after partial nephrectomy. A 77-year-old man underwent a partial nephrectomy for a right renal mass. The histopathological results showed clear cell renal cell carcinoma, G1>G2, pT1a. Four and a half years after surgery, a nodule appeared in the retroperitoneal space on CT. FDG-PET CT showed increased uptake in the nodule, indicating local recurrence of carcinoma. A right nephrectomy was performed. The histopathological diagnosis was fat necrosis.

Development and nationwide validation of kidney graft injury markers using urinary exosomes and microvesicles (complete English translation of the Japanese version).

BACKGROUND: Non-invasive, prompt, and proper detection tools for kidney graft injuries (KGIs) are awaited to ensure graft longevity. We screened diagnostic biomarkers for KGIs following kidney transplantation using extracellular vesicles (EVs; exosomes and microvesicles) from the urine samples of patients. METHODS: One hundred and twenty-seven kidney recipients at 11 Japanese institutions were enrolled in this study; urine samples were obtained prior to protocol/episode biopsies. EVs were isolated from urine samples, and EV RNA markers were assayed using quantitative reverse transcription polymerase chain reaction. Diagnostic performance of EV RNA markers and diagnostic formulas comprising these markers were evaluated by comparison with the corresponding pathological diagnoses. RESULTS: EV CXCL9, CXCL10, and UMOD were elevated in T-cell-mediated rejection samples compared with other KGI samples, while SPNS2 was elevated in chronic antibody-mediated rejection (cABMR) samples. A diagnostic formula developed through Sparse Logistic Regression analysis using EV RNA markers allowed us to accurately (with an area under the receiver operator characteristic curve [AUC] of 0.875) distinguish cABMR from other KGI samples. EV B4GALT1 and SPNS2 were also elevated in cABMR, and a diagnostic formula using these markers was able to distinguish between cABMR and chronic calcineurin toxicity accurately (AUC 0.886). In interstitial fibrosis and tubular atrophy (IFTA) urine samples and those with high Banff chronicity score sums (BChS), POTEM levels may reflect disease severity, and diagnostic formulas using POTEM detected IFTA (AUC 0.830) and high BChS (AUC 0.850). CONCLUSIONS: KGIs could be diagnosed with urinary EV mRNA analysis with relatively high accuracy.

Relationship Between Physical Activity and Estimated Glomerular Filtration Rate in Renal Transplant Recipients: A Cross-sectional Study Analyzing Isotemporal Substitution Model.

OBJECTIVES: Successful renal transplantation reduces mortality rates. However, the decline in the estimated glomerular filtration rate (eGFR) after transplantation is strongly associated with premature mortality in renal transplant recipients (RTRs). Physical activity (PA) is a modifiable lifestyle factor with the potential to maintain or improve eGFR. However, the effects of the type or intensity of PA and sedentary behavior (SB) on eGFR in RTRs remain unclear. The purpose of this study was to clarify the association between accelerometry-measured PA and SB and eGFR in RTRs using isotemporal substitution (IS) analysis. METHODS: A total of 82 renal transplant outpatients participated in this cross-sectional study, of which 65 (average age, 56.9 years; average time post-transplant, 83.0 months) were finally analyzed. All RTRs wore a triaxial accelerometer to measure PA for 7 consecutive days. The measured PA was classified based on intensity into light PA, moderate-to-vigorous PA (MVPA), and SB. The association of each type of PA with eGFR was examined using multi-regression analyses of single-factor, partition, and IS models. The IS model was applied to examine the estimated effects of substituting 30 minutes of SB with an equal amount of time of light PA or MVPA on eGFR. RESULTS: The partition model showed that MVPA was an independent explanatory variable for eGFR (ß = 5.503; P < .05), and the IS model identified that the substitution of time spent in SB with MVPA led to improvements in eGFR (ß = 5.902; P < .05). CONCLUSIONS: The present study suggests that MVPA has an independent and positive association with eGFR, and replacing 30 minutes of SB with MVPA after renal transplantation might lead to the maintenance or improvement of eGFR in RTRs.

Remitting seronegative symmetrical synovitis with pitting edema syndrome induced by pembrolizumab in patient with urothelial carcinoma.

Introduction: Recent introduction of immuno-oncology drugs such as pembrolizumab has resulted in improved outcomes for urothelial carcinoma patients. However, immune-related adverse events generally show great variance and are often difficult to diagnose and control. Case presentation: An 84-year-old Japanese male with urothelial carcinoma metastasis to the lungs after a laparoscopic left radical nephroureterectomy procedure was treated with pembrolizumab, an immuno-oncology drug, as second-line therapy. At week 6, inflammatory arthralgia involving the hands and shoulder joints, and edema of the hands were presented. The diagnosis was remitting seronegative symmetrical synovitis with pitting edema syndrome. Pembrolizumab was discontinued, and oral corticosteroid therapy was started. Two months later, pembrolizumab treatment was resumed because of a significant improvement in patient condition. Conclusion: Although rare, immune-related adverse events are occasionally encountered during the use of immune-oncology drugs; thus, early diagnosis and appropriate treatment are important.

Everolimus Reduces Cancer Incidence and Improves Patient and Graft Survival Rates after Kidney Transplantation: A Multi-Center Study.

Kidney transplantation can prevent renal failure and associated complications in patients with end-stage renal disease. Despite the good quality of life, de novo cancers after kidney transplantation are a major complication impacting survival and there is an urgent need to establish immunosuppressive protocols to prevent de novo cancers. We conducted a multi-center retrospective study of 2002 patients who underwent kidney transplantation between 1965 and 2020 to examine patient and graft survival rates and cumulative cancer incidence in the following groups categorized based on specific induction immunosuppressive therapies: group 1, antiproliferative agents and steroids; group 2, calcineurin inhibitors (CNIs), antiproliferative agents and steroids; group 3, CNIs, mycophenolate mofetil, and steroids; and group 4, mammalian target of rapamycin inhibitors including everolimus, CNIs, mycophenolate mofetil, and steroids. The patient and graft survival rates were significantly higher in groups 3 and 4. The cumulative cancer incidence rate significantly increased with the use of more potent immunosuppressants, and the time to develop cancer was shorter. Only one patient in group 4 developed de novo cancer. Potent immunosuppressants might improve graft survival rate while inducing de novo cancer after kidney transplantation. Our data also suggest that everolimus might suppress cancer development after kidney transplantation.

Incidence and mortality of post-transplant lymphoproliferative disorders after kidney transplantation: A real-world retrospective analysis in Japan.

OBJECTIVES: Post-transplant lymphoproliferative disorder is a potentially life-threatening complication that has a greater risk of occurrence in the setting of immunosuppression and oncogenic viral infections after transplant surgery. Few studies have reported the cumulative incidence, histological subtypes and clinical outcomes of this disorder in kidney transplant recipients. METHODS: We retrospectively investigated 34 post-transplant lymphoproliferative disorder patients diagnosed out of the 1210 kidney transplant recipients who had undergone the surgery at the two largest centers in Japan between January 1983 and December 2017. RESULTS: A total of 32 patients (94.1%) developed late-onset post-transplant lymphoproliferative disorder (diagnosed 1 year after transplantation). The cumulative incidence rates were 0.76% and 1.59% at 5 and 10 years post-transplantation, respectively. The central nervous system was the most common site (35.3%, 12/34). Overall survival was similar between patients with and without central nervous system lesions (P = 0.676). Of all of the cases, 23.5% (8/34) were detected through cancer screening. Importantly, patients with screening-detected post-transplant lymphoproliferative disorder had better overall survival than those with the disorder who had been symptom detected (P = 0.0215). Overall survival was significantly reduced in patients who developed the disorder compared with those who did not (P = 0.0001). CONCLUSIONS: Post-transplant lymphoproliferative disorder was more likely to occur in the late post-transplantation period, which showed that long-term medical examination for transplant recipients is required. Based on our findings, we propose vigilant, long-term, cancer screening in kidney transplant recipients.

[Ectopic Ureterocele of Adult Male with Urination Difficulty : A Case Report].

Ectopic ureteroceles is sometimes noted in children as an incidental finding in antenatal ultrasonography results or because of symptoms related to a urinary tract infection. In contrast, it is rarely noted in adults, with only 18 cases in Japan presented in literature. We report here a 30-year-old adult male with an ectopic ureterocele discovered due to urination difficulty. The patient noted a poor urine stream and macroscopic hematuria after exercise, and over time needed manual compression on the lower abdomen for urination. Computed tomography results revealed a 35 mm right ureterocele containing a 7.0 mm stone. Cystoscopy showed the ureterocele protruding into the prostatic urethra, which was thought to be the cause of urination difficulty. Transurethral resection of the ureterocele and lithotripsy for the stone were performed. The right ureteral orifice was not visualized during the operation. Resection was performed from the bladder neck side so that the ureterocele wall did not interfere with urination and the calculus was crushed with a pneumatic lithotripter (LithoClast®). Urination difficulty was improved following the procedures. Urinary cystourethrography performed two weeks postoperatively confirmed no vesicoureteral reflux. No symptoms of dysuria or fever were noted at a follow-up visit two months after the operation.

Perirenal fat metastasis of prostate cancer.

A 72-year-old male underwent an abdominal CT scan, which revealed a 17-mm nodular incidentaloma in fat tissue in the left perirenal space. Retroperitoneoscopic surgery was performed to remove the tumor and histopathological results revealed a PSA-positive adenocarcinoma, which was diagnosed as a metastatic lesion associated with prostate cancer. PSA was high at 30.083 ng/ml and MRI findings showed extracapsular extension of prostate cancer in the left peripheral zone of the prostate gland. Biopsy results with a Gleason score of 4 + 4 confirmed the diagnosis of prostate cancer. The case was diagnosed as prostate cancer metastasis in perirenal fat tissue.

Cumulative cancer incidence and mortality after kidney transplantation in Japan: A long-term multicenter cohort study.

Kidney transplantation is the most promising treatment to improve mortality and life quality in end-stage kidney disease; however, cancer remains a leading cause of death. Several factors including immunosuppressants might be associated with a gradual increase in cumulative cancer incidence after kidney transplantation. Risk factors for cancer and overall and cancer-specific survival were analyzed in 1973 kidney transplant recipients from three study institutions in Japan. The 5-, 10-, 20-, and 30-year overall and cancer-specific survival rates were 93.3%, 88.4%, 78.0%, and 63.6% and 99.4%, 98.0%, 95.3%, and 91.7%, respectively. The overall survival rate was significantly higher and the graft survival rate was significantly lower in recipients without cancer than in those with cancer. Older recipient age, longer dialysis duration before kidney transplantation, and history of transfusion were significant predictors of cancer. Dialysis duration before kidney transplantation was a prognostic factor of overall survival rate. Regarding cancer-specific survival rates, older recipient age and dialysis duration before kidney transplantation were prognostic factors of worse cancer-specific survival rates. The type of immunosuppressant was not associated with an increased cancer rate. Aggressiveness of immunosuppressant regimens or potent immunosuppressants might improve graft survival rate while inducing de novo cancer after kidney transplantation. Older age and longer dialysis duration before kidney transplantation were risk factors of cancer-specific survival rate.

[OUTCOMES OF BLADDER CANCER IN NONAGENARIANS].

(Objectives) We evaluated the chronological change in the number and proportion of elderly patients with bladder cancer. We also retrospectively investigated the clinical outcomes of bladder cancer in patients of ≥90 years of age. (Patients and methods) We evaluated the chronological change in the number and proportion of patients of ≥90 years of age who were clinically diagnosed with bladder cancer and who underwent transurethral resection of a bladder tumor (TUR-BT) at our hospital between 2008 and 2018. We also assessed the clinicopathological factors, perioperative outcomes, and clinical outcomes in bladder cancer patients of ≥90 years of age. (Results) The number and proportion of bladder cancer patients of ≥90 years of age increased with time. A total of 39 patients of ≥90 years of age underwent TUR-BT at our hospital, among whom 22 were diagnosed with primary bladder cancer. The median age was 91 years. No grade ≥III complications were observed after TUR-BT. Two out of 6 with pT1 disease underwent second TUR-BT. Two out of 7 with pT1 disease or carcinoma in situ received intravesical BCG therapy. Six deaths were observed during the study period, 2 of which were due to bladder cancer. At 1 and 3 years after TUR-BT, the overall survival rates of the 22 patients were 80.4% and 68.9%, respectively. (Conclusions) The number and proportion of elderly patients with bladder cancer increased with time. The current standard of care including second TUR-BT and intravesical BCG therapy for high-risk non-muscle invasive bladder cancer was underutilized in nonagenarians.

Implementation of repeat biopsy and detection of cancer after a diagnosis of atypical small acinar proliferation of the prostate.

Current guidelines recommend a repeat biopsy within 3-6 months after an initial diagnosis of atypical small acinar proliferation (ASAP) due to the high incidence of cancer detection on repeat biopsy. The current study sought to investigate practice patterns after a diagnosis of ASAP in a real-world setting and examine the clinicopathological outcomes of repeat biopsy. The departmental database of the Hyogo Prefectural Nishinomiya Hospital identified 97 of 1,218 patients with a diagnosis of ASAP on initial biopsy from 2011 to 2016. Clinical and pathological data were retrospectively analyzed. Of the 97 patients, 34 (35.1%) underwent a repeat biopsy. Patients with a repeat biopsy had a significantly higher prostate-specific antigen (PSA) velocity and shorter PSA doubling time than patients without a repeat biopsy (P=0.0002), and of these 34 patients with a repeat biopsy, 16 (47.1%) were diagnosed as having cancer. Multivariate logistic regression analysis revealed that a small prostate (P=0.0250) and advanced age (P=0.0297) were associated with cancer detection on repeat biopsy. Of the 16 cancers identified, 13 (81.6%) were diagnosed with a Gleason score >6. The results indicated that the implementation of a repeat biopsy for patients with ASAP could be affected by clinical characteristics in real-world settings, despite the current recommendation of guidelines endorsing immediate repeat biopsy. Prostate volume and age would aid in the decision-making process to perform repeat biopsy in patients with high PSA velocity and short PSA doubling time after a diagnosis of ASAP.

Metastatic bladder tumor from prostate cancer causing a ball valve-like obstruction in urination.

We report a rare case of prostate cancer that apparently metastasized to the bladder and formed a pedunculated mass that caused a ball valve-like obstruction in urination. A 57-year-old man with metastatic prostate cancer was referred to the emergency department for acute urinary retention. Cystoscopy and magnetic resonance imaging revealed a pedunculated mass measuring approximately 2 cm in size in the bladder neck that appeared to cause urinary obstruction in a ball valve-like manner. Transurethral resection of the bladder tumor was performed that resolved his symptom, and histopathological findings confirmed a diagnosis of poorly differentiated prostate adenocarcinoma.

Primary perirenal angiosarcoma: A preoperative diagnostic challenge.

Angiosarcoma arising in the retroperitoneal space is rare. We report a case of perirenal angiosarcoma presenting preoperative diagnostic difficulties. A 49-year-old man was referred to our department with left kidney mass. Specimens of CT-guided percutaneous needle biopsy of the mass did not contain any atypical cells suggestive of malignancy. A CT scan 6 months after embolization of the tumor revealed growth of the mass and two space-occupying lesions appearing in the liver. Laparoscopic resection of the left kidney with perirenal mass and one of the liver lesions was performed. Histopathological findings confirmed a diagnosis of perirenal angiosarcoma with hepatic metastases.

Malignancy With Immunosuppression After Renal Transplantation: A Competing Risk Analysis.

OBJECTIVES: This study analyzed clinical characteristics of renal transplant recipients who developed malignancy with immunosuppression after transplantation by applying a competing risk analysis to reduce the effects of competing events. METHODS: All patients who underwent renal transplantation at our institution from 1973 to 2017 were included in this analysis. All data were collected from patient medical records and retrospectively analyzed. The cumulative incidence of malignancy before allograft loss and its risk factors were calculated by a competing risk analysis, the Gray test, and the Fine-Gray proportional hazard model. RESULTS: Of the 596 recipients, 78 developed malignancies. The mean age at transplantation was 38.5 ± 13.1 years. The median time from transplantation to the initial malignancy was 147.0 (5.2-407.3) months. The most common initial malignancy was skin cancer (21.8%), followed by posttransplant lymphoproliferative disease (14.1%). The cumulative incidence of malignancy at 20 years was 16.2% according to a competing risk analysis, whereas the conventional Kaplan-Meier method estimated the cumulative incidence at 20 years to be 25.6%. Increasing age at transplantation was significantly associated with the incidence of malignancy (P = .0091). Overall 10-year survival rates of recipients with and without malignancy were 81.7% and 88.5%, respectively (P < .001). CONCLUSIONS: Results of time-to-event analysis must be interpreted with caution in situations with competing events when estimating the cumulative incidence of malignancy with immunosuppression after renal transplantation. Renal transplant recipients with increasing age should be more carefully monitored as a high-risk population for developing malignancies.

Keratinizing Squamous Metaplasia of the Urinary Bladder With White Hair-like Structures.

A 74-year-old woman presented to the urology clinic with a protruding mass in her urinary bladder detected by ultrasonography. She had no symptoms. Cystoscopy revealed a 1-cm lesion with a lock of 1-cm-long white hair-like structures on the right side of the bladder. White plaques were also noted covering some areas of the bladder. Transurethral resection of the lesion and biopsy of the white plaques were performed. Pathological examination confirmed a diagnosis of keratinizing squamous metaplasia of the bladder with no evidence of malignancy.

[Disturbance of Consciousness in a Patient with an Indwelling Lumbar-Peritoneal Shunt Following Retroperitoneal Laparoscopic Radical Right Nephrectomy : A Case Report].

An 83-year-old man with an indwelling lumbar-peritoneal (L-P) shunt (for idiopathic normal-pressure hydrocephalus) underwent retroperitoneal laparoscopic radical right nephrectomy for renal cell carcinoma (pT1aN0M0). Peritoneal perforation occurred intraoperatively, and he developed postoperative disturbance of consciousness. Computed tomography showed mild ventricular enlargement, which was attributed to L-P shunt failure secondary to increased pneumoperitoneum pressure. His level of consciousness was improved when we raised his head. Few reports have discussed complications observed during retroperitoneal laparoscopic surgery in patients with an indwelling L-P shunt. This case report discusses this topic along with a discussion of previously reported findings.

Evaluation of IgA1 O-glycosylation in Henoch-Schönlein Purpura Nephritis Using Mass Spectrometry.

BACKGROUND: Glomerular deposition of IgA1 is a common feature of Henoch-Schönlein purpura nephritis (HSPN) and is indistinguishable from that seen in IgA nephropathy (IgAN). Serum IgA1 is abnormally O-glycosylated in IgA nephropathy, which may contribute to the development of glomerular injury. Abnormal O-glycosylated IgA1 was also detected in HSPN using lectin enzyme-linked immunosorbent assay; however, this method cannot provide the exact structural information of O-glycans. Mass spectrometry is an effective means of quantification of O-glycans, and there is no report to evaluate IgA1 O-glycans in HSPN using mass spectrometry. MATERIALS AND METHODS: We investigated O-glycosylation profile in serum IgA1 from 7 HSPN recipients, 26 IgAN recipients, 25 recipients with other kidney diseases (OKDs), and 26 normal healthy donors using mass spectrometry. RESULTS: Of the 14 GalNac-Gal combinations detected using mass spectrometry, the percentage of the only 6GalNAc-2Gal combination was significantly different between HSPN and IgAN. The percentage of GalNAc 3 in HSPN recipients was significantly higher than that in OKDs recipients and healthy donors (P = .0027 and P < .0001, respectively). Inversely, the percentage of GalNAc 5 in HSPN recipients was significantly lower than that in OKDs recipients and healthy donors (P = .0008, P < .0001, respectively). Moreover, the Gal content and the Gal/GalNAc ratio of HSPN recipients were significantly lower than OKDs recipients and healthy donors. CONCLUSIONS: Examination of Henoch-Schönlein purpura recipients revealed that the number of GalNAc fell and the Gal attachment to GalNAc was reduced compared to other kidney diseases and healthy donors. The IgA1 O-glycosylation profile of HSPN was very similar to that of IgAN.

Immunoenzymatic Staining of Caveolin-1 in Formalin-Fixed Renal Graft Showing Chronic Antibody Mediated Rejection.

AIM: Caveolin-1 (CAV-1) is a molecule associated with endothelial cell dysfunction in chronic antibody-mediated rejection (CAMR) and considered to be a novel biomarker of CAMR. For immunohistochemical staining to reveal CAV-1 expression, most studies have used immunofluorescent stained frozen specimens, whereas formalin-fixed tissues have not been utilized. In the present study, we examined CAV-1 expression in specimens from CAMR patients using an immunoenzymatic technique with formalin-fixed tissues. METHODS: Eleven patients diagnosed with CAMR based on findings of transplanted renal biopsy samples were enrolled. Those biopsy specimens were formalin fixed and stained with CAV-1 using an immunoenzymatic method. Dye extent was evaluated by classifying that in peritubular capillaries (PTC) and glomerular capillaries (GBM) in 3 steps. We then compared the Banff scores for peritubular capillaritis (ptc), glomerulopathy (cg), and C4d using those results. RESULTS: CAV-1 expression was confirmed in vascular endothelium (PTC, GBM), while it was poor in epithelial cells. A Banff score for ptc and cg of 3 points was seen in 3 and 4 cases, of 2 points was seen in 1 and 4 cases, of 1 point was seen in 7 and 3 cases, and of 0 points was seen in 0 and 0 cases, respectively. In PTC, C4d and CAV-1 scores of 3 points were seen in 0 and 9 cases, of 2 points were seen in 2 and 2 cases, of 1 point was seen in 5 and 0 cases, and of 0 points were seen in 4 and 0 cases, respectively. As for GBM, C4d and CAV-1 scores of 3 points were seen in 8 and 7 cases, of 2 points were seen in 2 and 4 cases, of 1 point was seen in 0 and 0 cases, and of 0 points were seen 1 and 0 cases, respectively. CONCLUSION: CAV-1 expression in PTC had a score ≥2 in all cases, indicating that an adequate level of staining of formalin-fixed tissue was attained with the present immunoenzymatic technique. These results suggest that CAV-1 expression examined by the present method may be useful for identifying endothelial dysfunction.