Weekly low-dose docetaxel combined with estramustine and dexamethasone for Japanese patients with metastatic castration-resistant prostate cancer.

BACKGROUND: A low-dose chemotherapy consisting of docetaxel, estramustine and dexamethasone was investigated for its beneficial effect and feasibility in Japanese patients with metastatic castration-resistant prostate cancer (CRPC). METHODS: Seventy-two Japanese patients with metastatic CRPC were enrolled to receive docetaxel (25 mg/m(2) on days 2 and 9), estramustine phosphate (280 mg orally twice daily from day 1 to day 3 and from day 8 to day 10) and dexamethasone (0.5 mg orally twice daily) every 21 days. RESULTS: The median age of the patients was 72 years and 64 patients (89 %) had ≥grade 1 anemia at entry. The median total number of courses administered was 8.5 (range 1-93). Forty-two patients (58 %) had a prostate-specific antigen (PSA) decline of ≥50 %. The median progression-free survival and overall survival were 6 and 23 months, respectively. Fifteen patients (21 %) improved and 53 patients (74 %) were stable in their performance status. Of the 40 patients with bone pain, 25 patients (63 %) showed pain reduction. Among 71 patients assessable for their hemoglobin levels, 21 patients (30 %) achieved an increase of at least 1.0 g/dl. Of the 5 patients who terminated treatment because of ≥grade 3 toxicity, 4 patients had pneumonitis and one patient had anemia. Only one patient developed ≥grade 3 neutropenia. CONCLUSIONS: The low-dose combination of docetaxel, estramustine and dexamethasone is active and tolerable with beneficial effects on serum PSA levels, performance status, anemia and bone pain in Japanese patients with CRPC. This regimen is a reasonable option for elderly patients with bone disease at risk of hematologic toxicity.

[Case of prostate cancer associated with bisphosphonate-related osteonecrosis of the jaw followed by retropharyngeal abscess].

A 67-year-old man with castration-resistant prostate cancer associated with multiple bone metastases had been treated with zoledronic acid and docetaxel. Although there was no evidence of damage around the right lower jaw bone, the patient complained of pain in May 2011, which worsened during the next 2 weeks and was followed by difficulty with breathing. Computed tomographic (CT) findings of the cervical area showed swelling of the cervical tissue with air and tightening of the trachea, suggesting cellulitis caused by gas gangrene. He was intubated and treated with antibiotics. On the 12th hospital day, CT scan revealed a pharyngeal abscess and we performed a drainage operation. On the 20th hospital day, bone of the intraoral lower jaw was exposed, revealing that the infection was caused by osteonecrosis. Additional CT findings showed the abscess extending to the mediastinum and multiple liver metastases. Although antibiotic therapy was continued, the patient died of liver failure on the 61st day.

[A case of ductal adenocarcinoma of prostate associated with retroperitoneal multiple cysts].

A 61-year-old man came to our hospital with a complaint of lower abdominal pain. Computed tomography (CT) and magnetic resonance imaging (MRI) around his abdominal area showed large multiple cysts in the pelvis suggesting a malignant tumor. He showed high levels of serum carbohydrate antigen 19- 9 (CA19-9) and carcinoembryonic antigen (CEA). The complete diagnostic studies, including upper gastrointestinal endoscopy and colonoscopy examinations, failed to demonstrate the presence of alimentary primary tumors. With the diagnosis of cystic tumor in the pelvis, the operation was performed. The cysts adhered firmly to the surrounding organs including bladder and peritonium, which could not be resected completely. A histopathological diagnosis was papillary adenocarcinoma positive for prostate specific antigen (PSA). Because the level of serum PSA was 9.39 ng/ml, prostate biopsy was performed and ductal adenocarcinoma of prostate was revealed. After the operation, the levels of serum CA19-9 and CEA decreased to a normal level. Androgen deprivation therapy (ADT) was started, and the level of PSA was normalized one month later. Ductal adenocarcinoma forming cysts is rare. We reviewed 15 cases reported in the Japanese literature.

[A case of prostate cancer diagnosed by lymphadenectomy].

A 65-year-old man was referred to our hospital because of an elevated value of prostate specific antigen (PSA) (10.9 ng/ml). An eight-core prostate biopsy was negative. One year later, serum PSA increased to 55. 8 ng/ml and pelvic magnetic resonance imaging (MRI) showed a left external iliac lymph node enlargement. A ten-core prostate biopsy was negative. Six months later, the serum PSA increased to 88.1 ng/ml, but an seventeen-core prostate biopsy was negative again. A positron emission tomographycomputed tomography scan showed nothing other than increased uptake localized to the left enlarged external iliac lymph node. Pelvic lymphadenectomy was performed and histological examination, including immunohistological staining with PSA, confirmed lymph node metastasis from prostate cancer. Androgen deprivation therapy was started and 2 month later, serum PSA declined to below 1.0 ng/ml.

[A case of skin cancer diagnosed 21 days after renal transplantation].

The patient was a 67-year-old man who was started on peritoneal dialysis for treatment of diabetic nephropathy in March 2010. He received an ABO-compatible living-donor kidney transplant from his wife in October 2010. The immunosuppressive regimen consisted of tacrolimus, mycophenolate mofetil, steroid and basiliximab. Before the operation, a bump on his forehead/temple region that was increasing in size for years was noted. The bump had a scaly surface and the top of the bump was sloughed on postoperative day 14. Histological examination suggested malignancy. On postoperative day 21, a skin biopsy was performed by dermatologists and squamous cell carcinoma was confirmed. On postoperative day 36, wide excision and transposition flap procedures were performed by the plastic surgeon. At 15 months after transplantation, the kidney graft was functioning well with a serum creatinine level of 0.84 mg/dl and there was no sign of recurrence of the squamous cell carcinoma.

5α-reductase type 3 expression in human benign and malignant tissues: a comparative analysis during prostate cancer progression.

BACKGROUND: A third isozyme of human 5α-steroid reductase, 5α-reductase-3, was identified in prostate tissue at the mRNA level. However, the levels of 5α-reductase-3 protein expression and its cellular localization in human tissues remain unknown. METHODS: A specific monoclonal antibody was developed, validated, and used to characterize for the first time the expression of 5α-reductase-3 protein in 18 benign and 26 malignant human tissue types using immunostaining analyses. RESULTS AND CONCLUSIONS: In benign tissues, 5α-reductase-3 immunostaining was high in conventional androgen-regulated human tissues, such as skeletal muscle and prostate. However, high levels of expression also were observed in non-conventional androgen-regulated tissues, which suggest either multiples target tissues for androgens or different functions of 5α-reductase-3 among human tissues. In malignant tissues, 5α-reductase-3 immunostaining was ubiquitous but particularly over-expressed in some cancers compared to their benign counterparts, which suggests a potential role for 5α-reductase-3 as a biomarker of malignancy. In benign prostate, 5α-reductase-3 immunostaining was localized to basal epithelial cells, with no immunostaining observed in secretory/luminal epithelial cells. In high-grade prostatic intraepithelial neoplasia (HGPIN), 5α-reductase-3 immunostaining was localized in both basal epithelial cells and neoplastic epithelial cells characteristic of HGPIN. In androgen-stimulated and castration-recurrent prostate cancer (CaP), 5α-reductase-3 immunostaining was present in most epithelial cells and at similar levels, and at levels higher than observed in benign prostate. Analyses of expression and functionality of 5α-reductase-3 in human tissues may prove useful for development of treatment for benign prostatic enlargement and prevention and treatment of CaP.

Pulmonary metastasectomy in patients with renal cell carcinoma: a single-institution experience.

BACKGROUND: Pulmonary metastasectomy in patients with renal cell carcinoma (RCC) remains controversial. The purpose of our analysis was to explore the outcome of patients with RCC who underwent pulmonary metastasectomy at our institution. METHODS: We reviewed data on 25 patients who underwent resection of lung metastasis from 1998 to 2008 at our institution. RESULTS: All patients were treated by radical nephrectomy for primary RCC. Progression-free survival (PFS) ranged from 0.3 to 198.8 months (median 7.4 months), and overall survival (OS) ranged from 2.4 to 198.8 months (median 33.9 months). The 5-year PFS rate was 24.9%, and the OS rate was 35.5%. Although differences in the resectability of the metastasectomy and OS were not significant in univariate or multivariate analyses, the relationship between PFS and the radicality of pulmonary metastasectomy was significant in both the univariate and multivariate analyses (P = 0.004, 0.012, respectively). CONCLUSIONS: The results of pulmonary metastasectomy for patients with RCC at our institution indicate that pulmonary metastasectomy should be performed only when the pulmonary metastasis can be completely resected. Additional studies are therefore necessary to evaluate the prognostic factors and to determine the selection criteria for pulmonary metastasectomy in the new era of molecular-targeted agents.

SERPINE2 is a possible candidate promotor for lymph node metastasis in testicular cancer.

Testicular germ cell tumors (TGCTs) commonly metastasize to the lymph node or lung. However, it remains unclear which genes are associated with TGCT metastasis. The aim of this study was to identify gene(s) that promoted human TGCT metastasis. We intraperitoneally administered conditioned medium (CM) from JKT-1, a cell-line from a human testicular seminoma, or JKT-HM, a JKT-1 cell sub-line with high metastatic potential, into mice with JKT-1 xenografts. Administration of CM from JKT-HM significantly promoted lymph node metastasis. A cDNA microarray analysis showed that JKT-HM cells highly expressed the Serpine peptidase inhibitor, clade E, member 2 (SERPINE2), which encodes a secreted protein. Administration of CM from SERPINE2-silenced JKT-HM cells inhibited lymph node metastasis in the xenograft model, compared with administration of CM from JKT-HM cells. There was no significant difference in xenograft volume. Moreover, administration of CM from SERPINE2-over-expressing JKT-1 was likely to promote lymph node metastasis in the xenograft model. There was no difference in the in vitro proliferation or migration of JKT-1 cells cultured with CM from JKT-HM cells, compared to that with CM from JKT-1. There was no promotion of proliferation or lymphangiogenesis in the xenografts, as measured by Ki-67 and LYVE-1 immunohistochemistry, respectively. Although we could not clarify how SERPINE2 promoted lymph node metastasis, it may be a promoter in the development of lymph node metastasis in the human seminoma cells in a mouse xenograft model.

Decreased immunostaining for macrophage scavenger receptor is associated with poor prognosis of prostate cancer.

OBJECTIVE: The aim of this study is to evaluate the expression of the macrophage scavenger receptor (MSR) in prostate needle biopsy specimens as a possible prognostic factor for prostate cancer. As MSR reportedly has a role in recognizing foreign pathogenic substances, MSR-positive inflammatory cells are often detected in solid tumours, and there is a correlation between the relative risk of prostate cancer and polymorphism of the MSR gene. PATIENTS AND METHODS: MSR was evaluated by immunostaining in needle biopsies of the prostate from 135 patients who were confirmed to have prostate cancer. Among these men, 70 were treated by radical prostatectomy or by radiotherapy as definitive therapy; the other 65 were treated by hormonal therapy because of advanced disease or age. Needle-biopsy specimens were sectioned at 5 microm and immunostained with a monoclonal antibody against MSR. Six microscopic (x400) fields around the cancer foci were selected in each case for analysis. RESULTS: The median number of MSR-positive cells (MSR count) in each case was 24. There was an inverse correlation between the MSR count and Gleason score and clinical stage. The MSR count was lower in patients with biochemical (prostate-specific antigen, PSA) failure than that in those with no PSA failure (P < 0.001). In all patients, the recurrence-free survival (RFS) rate was significantly higher in those with a high MSR count (> or =24) than that in those with low MSR count (<24, P < 0.001). Moreover, for patients treated by definitive or hormonal therapy, the RFS rates in those with a higher MSR count were higher than in those with a lower MSR count (P < 0.001 and 0.014, respectively). Cox multivariate analysis showed that the MSR count was a prognostic factor for prostate cancer in addition to extraprostatic extension and Gleason score (P = 0.002, 0.038 and 0.011, respectively). CONCLUSION: The results of immunostaining of MSR in needle-biopsy specimens is a prognostic factor for prostate cancer.

Brain metastases from testicular germ cell tumors: a retrospective analysis.

OBJECTIVES: To review our series of testicular germ cell tumors with brain metastases and to establish an optimal treatment strategy for them. METHODS: Twenty-seven cases of testicular germ cell tumors from three institutions were retrospectively reviewed. RESULTS: Twenty-six were non-seminomatous tumors and only one was a seminoma. Based on the International Germ Cell Consensus Classification, two cases were classified as good prognosis, seven as intermediate prognosis and 18 as poor prognosis. Chemotherapy was carried out in all patients. Additionally, whole-brain radiotherapy was performed in 10 cases, stereotactic radiosurgery in six, whole-brain radiotherapy combined with stereotactic radiosurgery in three and complete surgical resection in five. Three patients received chemotherapy only. Cancer-specific 5- and 10-year survival rates were both 35.9%. The prognosis of those with brain metastases at the time of diagnosis tended to be better than those developing brain metastases during treatment. Those with a single brain metastasis showed significantly better survival than those with multiple brain metastases. No other significant prognostic factor was found at multivariate analysis. CONCLUSION: Testicular germ cell tumors with brain metastases can be managed with the combination of whole-brain radiotherapy, stereotactic radiotherapy, and/or surgical resection in combination with chemotherapy.

The growth-inhibitory effects of dexamethasone on renal cell carcinoma in vivo and in vitro.

BACKGROUND: Recently, several kinase inhibitors have been reported to exert stronger growth inhibitory effects on metastatic renal cell carcinomas (RCCs) than cytokines such as interferons (IFNs) and interleukin-2 (IL-2). On the contrary, the adverse effects of these drugs are also severe. The aim of this study is to analyze the growth-inhibitory effects of DEXamethasone (DEX) on RCC in vivo and in vitro. METHODS: The MTT assay was performed using three RCC cell lines, OUR-10, Caki-1, and NC65. OUR-10 cells were subcutaneously transplanted to the dorsal area of nude mice. The nuclear translocation of glucocorticoid receptor (GR) and NF-kappa B was examined using appropriate antibodies. Concentrations of interleukin-6 (IL-6), IL-8, and vascular endothelial cell growth factor (VEGF) in the conditioned media and cytosol were measured by enzyme-linked immunosorbent assay (ELISA). RESULTS: All three RCC cell lines responded to DEX treatment. The growth of OUR-10 xenografts was significantly inhibited by administration of DEX. GR was translocated into the nucleus on DEX treatment. Intracellular IL-6, as well as IL-6 in the conditioned medium, decreased in OUR-10 cells following treatment with increasing amounts of DEX. Concentrations of IL-8 and VEGF in the conditioned medium of OUR-10 and NC65 cells also decreased following DEX treatment, with the inhibition of nuclear translocation of NF-kappa B. CONCLUSION: DEX treatment is a candidate for advanced RCC therapy by inhibiting the activation of NF-kappa B and its downstream products such as IL-6, IL-8 and VEGF.

Prostate cancer mediates osteoclastogenesis through two different pathways.

The present study was undertaken to test the effects of prostate cancer cell lines (LNCaP, DU145, PC3, and MDA PCa 2b) on osteoclastogenesis. Crude conditioned medium (CM) from all four prostate cancer cell lines enhanced expression of the mRNA for receptor activator of NF-kappaB ligand (RANKL) in a mouse osteoblast cell line, MC3T3-E1; however, CM had no effect on expression of osteoprotegerin (OPG) mRNA. Coculture of MC3T3-E1 with prostate cancer cells yielded similar results. The number of mature osteoclasts induced by soluble RANKL increased significantly when osteoclast precursor cells were cultured with CM from LNCaP and DU145 cells. CM from LNCaP and DU145 cells also induced maturation from precursor in the absence of soluble RANKL, and this effect was not blocked by OPG. Addition of CM from DU145 cells increased expression of MMP-9 mRNA by osteoclast precursors. Our findings indicate that prostate cancer mediates osteoclastogenesis through induction of RANKL expression by osteoblasts and through direct actions on osteoclast precursors mediated by some factors other than RANKL.

[Urethral stent (Memotherm) for the treatment of benign prostatic hyperplasia].

We used a urethral stent for management of high-age and high-risk patients with benign prostatic hyperplasia (BPH) who needed surgical therapy. Nine patients were treated by this method. Chief complaints were urinary retention in 6 patients, dysuria with much residual urine in 2 and dysuria in 1. Blood loss and complications of the method were minimal. Postoperatively, 8 of the patients were able to void and on the average, residual urine of the patients was approximately 10 ml. Implantation of the urethral stent is a safe and non-invasive therapy for the patients who are unsuitable for invasive therapy.

[Sarcomatoid carcinoma of the urinary bladder: a case report].

A 63-year-old man was admitted to our hospital for a bladder tumor. Drip infusion pyelography, computerized tomography (CT) and magnetic resonance imaging suggested the presence of a large invasive tumor in the right wall of the bladder. Histopathological findings by transurethral resection of bladder tumor showed the presence of sarcomatous and carcinomatous elements. Immunohistochemical examination showed that the sarcomatous component did not stain for S-100 protein or for smooth muscle actin but it stained for epithelial markers. Under the diagnosis of sarcomatoid carcinoma, we performed a total cystectomy and ileal conduit without chemotherapy or radiation. A follow-up CT taken at four months postoperatively showed no evidence of recurrence.

[48XXYY Klinefelter's syndrome with recurrent foot ulcers: a case report].

A case of 48XXYY Klinefelter's syndrome diagnosed with foot ulcers, in a 43-year-old man, is reported. He presented to the Department of Dermatology in our hospital with the chief complaint of recurrent foot ulcers. He was referred to us because of atrophic external genitalia. The present condition and endocrinological examination suggested Klinefelter's syndrome. Chromosomal analysis revealed that his chromosomal type is 48XXYY. This is the 24th case of Klinefelter's syndrome with 48XXYY chromosome and is the 5th case associated with foot ulcers in Japan. Here we report this case together with a brief review of the previously reported cases.

[Squamous cell carcinoma of the renal pelvis with giant hydronephrosis].

We report a case of squamous cell carcinoma of renal pelvis associated with giant hydronephrosis. A 71-year-old woman presented to our hospital with a complaint of abdominal fullness due to the right giant hydronephrosis. Although the diagnosis of her hydronephrosis was made about 20 years ago at another hospital, it had been left untreated. Computed tomography showed the right hydronephrosis of 20 x 20 x 25 cm in diameter and no evidence of tumor or calculus in the right urinary tract. For relief of her complaint, right nephrectomy was performed. The fluid content was bloody and 4,200 ml in volume. Histological examination revealed a flat type squamous cell carcinoma of the renal pelvis. This is the 30th case of renal pelvic malignant tumor associated with giant hydronephrosis reported in Japan. The literature was reviewed and the management of giant hydronephrosis was discussed.

Excision repair cross-complementing group 1 may predict the efficacy of chemoradiation therapy for muscle-invasive bladder cancer.

PURPOSE: Chemoradiation therapy (CRT) is now widely recognized as bladder-preserving therapy for muscle-invasive bladder cancer (MIBC). However, some patients who fail CRT may miss the chance to be cured by cystectomy. Therefore, it is important to select patients with MIBC who are expected to have a good response to CRT. Several reports indicate that the excision repair cross-complementing group 1 (ERCC1) gene is associated with resistance to cisplatin and radiation therapy. In this study, we examined the correlation between ERCC1 and CRT in vitro and in vivo in bladder cancer. EXPERIMENTAL DESIGN: Bladder cancer cell lines T24, 5637, Cl8-2 (multidrug-resistant subline of T24), and CDDP10-3 (cisplatin-resistant subline of T24) were used for in vitro assays to measure ERCC1 expression level and growth inhibition with cisplatin or ionizing radiation (IR). We then examined by immunohistochemistry that whether ERCC1 nuclear staining correlates with the efficacy of CRT using cisplatin in 22 patients with MIBC. RESULTS: Cl8-2 cells expressed ERCC1 mRNA 5.96-fold higher than did T24. Cl8-2 and CDDP10-3 were more resistant to cisplatin or IR than was T24. Resistance to IR, but not to cisplatin, was removed by suppressing ERCC1 using siRNA in both Cl8-2 and CDDP10-3 cells. In immunohistochemistry with ERCC1, 6 of 8 positive cases did not have complete response to CRT, whereas 12 of 14 negative cases had complete response. Sensitivity and specificity were 75% and 85.7%, respectively (P = 0.008). CONCLUSION: Although further study is needed, ERCC1 expression level may predict the efficacy of CRT for MIBC.

Paclitaxel, ifosfamide, and nedaplatin (TIN) salvage chemotherapy for patients with advanced germ cell tumors.

BACKGROUND: The paclitaxel, ifosfamide, and cisplatin regimen has been used to treat metastatic testicular cancer with successful results. We investigated the usefulness of a paclitaxel, ifosfamide, and nedaplatin (TIN) regimen as salvage therapy for patients with advanced testicular germ cell tumors (GCTs). METHODS: Eight patients with advanced GCTs were treated with TIN. The treatment was performed as salvage therapy for cases refractory to therapies, such as bleomycin, etoposide and cisplatin, and irinotecan with nedaplatin. The TIN regimen consisted of paclitaxel (200 mg/m(2)) by 24-h infusion on day 1, followed by ifosfamide (1.2 g/m(2)) infusions over 2 h on days 2-6, and nedaplatin (100 mg/m(2)) given over 2 h on day 2. RESULTS: Seven out of eight patients achieved a disease-free status after chemotherapy, followed by surgical resection of the residual tumor. Six of the seven patients have continued to show no evidence of disease after salvage therapy, with a median follow-up period of 27 months, but one patient developed a 'growing teratoma syndrome' in the mediastinum 31 months after TIN chemotherapy. All patients developed grade 4 leukocytopenia. However, it could be managed by using granulocyte colony-stimulating factor. Only one patient developed grade 2 sensory neuropathy and no patient developed nephrotoxicity. CONCLUSION: The TIN regimen was efficacious and well-tolerated as salvage chemotherapy for Japanese patients with advanced GCTs.

Sesquiterpene lactone parthenolide suppresses tumor growth in a xenograft model of renal cell carcinoma by inhibiting the activation of NF-kappaB.

The transcription factor nuclear factor-kappaB (NF-kappaB) has been shown to be constitutively activated in various human malignancies, including leukemia, lymphoma and a number of solid tumors. NF-kappaB regulates the transcriptional of genes important for tumor invasion, metastasis and chemoresistance. The sesquiterpene lactone parthenolide, an inhibition of NF-kappaB, has been used conventionally to treat migraines and inflammation. In this study, renal cancer cell lines OUR-10 and ACHN were used for in vitro experiments to evaluate growth-inhibitory effects of parthenolide. An OUR-10 xenograft model in nude mice was also used to investigate the in vivo growth-inhibitory effects of parthenolide. Apoptosis in response to treatment of OUR-10 cells with parthenolide was confirmed. Localization of NF-kappaB in response to parthenolide treatment was examined of by immunofluorostaining of OUR-10 cells with antibody against NF-kappaB p65 and by Western blot analysis of OUR-10 cell and tumor nuclear and cytosol fraction. Parthenolide effectively inhibited proliferation of cultured OUR-10 cells and triggered apoptosis in vitro. Subcutaneous injection or oral administration of parthenolide showed significant tumor growth inhibition in the xenograft model via decreased production of interleukin-8 (IL-8) or vascular endothelial growth factor (VEGF). Immunohistochemistry and Western blot analysis showed decreased nuclear localization of NF-kappaB and phosphorylated NF-kappaB protein and subsequently expression of MMP-9, Bcl-xL and Cox-2 in response to parthenolide treatment. These results indicate that parthenolide is a useful in the treatment of renal cell carcinoma and acts via inhibition of NF-kappaB.

Somatic mutations of the von Hippel-Lindau disease gene in renal carcinomas occurring in patients with long-term dialysis.

BACKGROUND: Renal cell carcinoma (RCC) frequently occurs in patients with long-term dialysis. Long-term dialysis causes distinctive pathological changes in the kidney, which is known as acquired cystic disease of the kidney (ACDK). It is of great interest to know whether RCCs occurring in the dialytic kidneys harbour the same or similar mutations of the von Hippel-Lindau (VHL) gene as conventional dialysis-unrelated clear cell RCCs so often do. METHODS: Renal cancer tissues (eight clear cell, two papillary, one Bellini duct and three of the so-called dialysis-specific renal carcinomas) from 13 patients undergoing long-term dialysis were examined for somatic mutations of the VHL disease gene. By means of laser capture microdissection, cancerous and surrounding non-cancerous renal tissues from dialytic patients were subjected to PCR-based direct sequencing of the VHL gene. RESULTS: Direct forward and reverse sequencing showed that three tumours possessed VHL gene mutations (713delG, 500-504del5-bp and 709A>G). These three mutations were identified in clear cell carcinomas occurring in association with end-stage renal disease undergoing dialysis for 194, 147 and 125 months. None of the non-tumour tissues or other carcinoma tissues analysed, including dialysis-specific carcinoma, possessed VHL gene mutations. CONCLUSION: These results indicate that VHL tumour-suppressor gene mutation is involved in clear cell carcinoma in association with long-term dialysis. Mutation of the VHL gene was not found in any of the dialysis-specific RCCs studied herein.