Proliferative activity of the parathyroid cells in rats with secondary hyperparathyroidism.

Proliferative kinetics of parathyroid cells in secondary hyperparathyroidism (HPT) are still unknown. We examined the histopathological changes and proliferative activity of parathyroid cells in spontaneously hypercholesterolemic (SHC) rats that exhibit secondary HPT and in normal Sprague Dawley (SD) rats from 3 weeks to 32 weeks of age. Proliferative activity [proliferating cell nuclear antigen(PCNA) labeling index], evaluated by means of immunohistochemical examination of PCNA, declined in SD rats with age from 10.8% at 3 weeks of age to 0.15% at 32 weeks of age. In SHC rats, a PCNA labeling index of 11.6% declined to 3.12% at 14 weeks of age and rebounded to 6.15% at 26 weeks of age. Parathyroid glands increased in size as determined by the maximum cross-sectional area, but in SHC rats, the increase was significantly greater, paralleling the progression of renal dysfunction, and at 32 weeks they were almost three times larger than in SD rats. Parathyroid hormone (PTH) levels in SHC rats also rose sharply after 20 weeks and reached 611 pg/ml at 32 weeks, while PTH in SD rats remained unchanged at approximately 110 pg/ml. This study showed that in the course of developing HPT in SHC rats, there is a large increase in the size of the parathyroid gland, a concomitant increase in PTH levels, and a PCNA labeling index that is higher than in normal SD rats.

[A case of bilateral renal cell carcinoma showing a rapid course of death in a long-term hemodialysis patient due to polycystic kidney].

A case of bilateral renal cell carcinoma in a 42-year-old polycystic kidney male is reported. He had been treated with hemodialysis for 22 years. An abnormal small mass was found in one of the left renal cystic lesions by screening ultrasonography and CT scan at the 19th year of the hemodialysis. Left radical nephrectomy was performed and the histological diagnosis was a renal cell carcinoma (RCC). There was no evidence of recurrence and metastasis, however, he presented with asymptomatic macrohematuria two years after the operation. CT scan demonstrated the rapidly progressing right renal tumor and multiple para-aortic lymph node swelling. Right nephrectomy and lymphadenectomy were performed and pathological examination showed the advanced RCC with multiple lymph node metastasis. Eleven months after the second operation followed by interferon therapy. he died of multiorgan metastasis of the RCC. This is the first bilateral RCC case in polycystic kidney patient treated with hemodialysis in Japan.

[Successful complete androgen blockade (CAB) therapy for prostatic cancer detected from multiple lung metastases: a case report].

Prostatic cancer is rarely diagnosed by detection of lung metastases. We report a case of prostatic cancer in a 73-year-old man detected by abnormalities in chest X-ray and serum prostate specific antigen (PSA) level. He was initially admitted to our hospital due to elevation of PSA level. On the first transperineal prostatic needle biopsy, prostatic cancer was not detected and he was followed. Seven months after the first biopsy, chest X-ray revealed multiple abnormal nodules in the lung fields bilaterally and PSA level was again elevated. A second prostatic biopsy and whole-body examination were performed, and he was diagnosed with moderately differentiated prostatic adenocarcinoma with multiple lung metastases. Complete androgen blockade therapy was performed immediately. Two months after the beginning of treatment, PSA level was normalized and the multiple lung metastases had completely disappeared. There has been no evidence of recurrence or PSA relapse 24 months after detection of the prostatic cancer. This is the 26th case of prostatic cancer diagnosed in Japan following detection of multiple lung metastases.

Immunohistochemical expression of P-glycoprotein in the rat urinary bladder and the effect of verapamil on intravesical chemotherapy.

BACKGROUND: The expression of P-glycoprotein (Pgp) is thought to be common in bladder epithelium and the multidrug resistance mediated by Pgp must be considered to improve the efficacy of chemotherapy for bladder tumors. METHODS: The expression of Pgp in normal and tumor tissue of the rat urinary bladder was first examined immunohistochemically. The effect of verapamil, an expected modulator of Pgp, on intravesical chemotherapy of the rats was then investigated. RESULTS: Pgp was immunohistochemically detected in normal epithelium and in tumor tissue of the rat urinary bladder. In those normal and tumor-bearing bladders, verapamil promoted the uptake of intravesically instilled pirarubicin, but the efflux of intracellular accumulated pirarubicin was observed subsequently in both conditions with and without verapamil. The drug concentration decreased more rapidly in the verapamil group than in the control group. CONCLUSIONS: Verapamil is thought to be useful in promoting uptake of intravesically instilled pirarubicin, but it did not appear to be so efficient at limiting the efflux of intracellular accumulated pirarubicin.

Early stage of urolithiasis formation in experimental hyperparathyroidism.

PURPOSE: We have previously noted marked acceleration in the proliferative activity of parathyroid cells in rats with spontaneous hypercholesterolemia and secondary hyperparathyroidism. Using this proliferative potential we investigated whether transplantation of these enlarged parathyroids into normal rats would induce hyperparathyroidism and renal stones. MATERIALS AND METHODS: We used 26-week-old male rats with spontaneous hypercholesterolemia as donors, and 5-week-old normal male Sprague-Dawley rats and rats with spontaneous hypercholesterolemia as recipients. Enlarged parathyroid glands were transplanted into group 1--Sprague-Dawley rats with no treatment, group 2--Sprague-Dawley rats that received FK-506 as an immuno-suppressor, group 3--rats with spontaneous hypercholesterolemia rats that underwent parathyroidectomy plus FK-506 administration and group 4--Sprague-Dawley rats that underwent parathyroidectomy plus FK-506 administration. Parathyroidectomy was performed in recipients before transplantation to ensure a low calcium condition. RESULTS: Grafts were rejected within 11 and 15 weeks in groups 1 and 2, respectively. In group 3, 78% of the grafts were successful even after 19 weeks. In group 4 graft survival was 30% at 15 weeks with complete rejection at 19 weeks. In group 3 gradually elevated serum parathyroid hormone was observed as well as stone plaques containing calcium oxalate and calcium phosphate in renal tubules located mainly in the corticomedullary junction. An increased number of plaques was associated with higher parathyroid hormone. CONCLUSIONS: Our study shows that transplanted parathyroid glands function with an immunosuppressive agent and the maintenance of hypocalcemic conditions, and they secrete sufficient parathyroid hormone to demonstrate hyperparathyroidism. Plaque in these kidneys indicates an early stage of urolithiasis caused by hyperparathyroidism.

[A case of Sertoli cell tumor of the testis].

A 24-year-old man was admitted to our hospital with the complaint of a painless mass in the left testis. Gynecomastia was not present. The serum levels of alpha fetoprotein and human chorionic gonadotropin-beta were not elevated. Ultrasound sonography showed a hypoechoic lesion in the left testis. There was no evidence of retroperitoneal lymph node enlargement or distant metastasis on computerized tomography. With a diagnosis of left testicular tumor, left high orchiectomy was done. The tumor measured 10 x 11 mm in size within the testis and was histologically diagnosed as benign Sertoli cell tumor. Immunohistochemcal analysis revealed negative findings with the tumor markers inhibin, CAM 5.2, pancytokeratin, EMA, and PLAP. No adjuvant therapy was performed. Twenty-six cases of Sertoli cell tumor of the testis in the Japanese literature are reviewed.

[Localized amyloidosis of the ureter and bladder treated effectively by occlusive dressing technique therapy using dimethyl sulfoxide: a case report].

We report here the first case of localized amyloidosis of the ureter and bladder to be treated effectively by occlusive dressing technique therapy using dimethyl sulfoxide. The patient was a 48-year-old woman whose chief complaint was macrohematuria and right back pain. Ultrasound sonography demonstrated right hydronephrosis and an intravesical mass in the region of the right ureteral orifice. Retrograde pyelography revealed severe stricture of the right lower ureter. Cystoscopy demonstrated a yellow submucosal tumor around the right ureteral orifice. We suspected urinary tract amyloidosis, and transurethral biopsy and resection of the intravesical mass were performed under right ureteral stenting. Histopathological diagnosis was amyloidosis. There was no evidence of systemic amyloidosis. To treat residual amyloidosis of the ureter and bladder, we performed occlusive dressing technique therapy using dimethyl sulfoxide every day. After 6 months of therapy, the right hydronephrosis disappeared, and there was no evidence of a recurrence of amyloidosis. We concluded that this therapy was very effective and safe for urinary tract amyloidosis.

[A case of bilateral testicular tumors with congenital adrenal hyperplasia].

We report a case of congenital adrenal hyperplasia (CAH) occurring in a 21-year-old man. He was found to have 21-hydroxylase deficiency shortly after birth in search for the cause of vomiting and adrenal insufficiency, and placed on steroid therapy. He had an uneventful childhood with normal onset of puberty. At the age of 21 years he was hospitalized with bilateral testicular masses. They were non-tender, firm and nodular on palpation. The levels of adrenocorticotrophic hormone (ACTH), 17 alpha-hydroxyprogesterone (17 alpha-OHP) were found to be elevated. Testicular biopsy revealed that the nodule comprised mainly eosinophilic sheets and nests and polygonal cells with abundant, granular cytoplasm, but no crystals of Reinke were seen. Testicular tumor with congenital adrenal hyperplasia is typically bilateral and develops in untreated or inadequately treated males with CAH.

[Renomedullary interstitial cell tumor: a case report].

Renomedullary interstitial tumor is a common tumor in the renal medulla, present in 26-41% of consecutive autopsy specimens. However clinically evident case is infrequent because this lesion is usually small (less than 3 mm). We report a case of renomedullary interstitial tumor in a 76-year-old woman. Ultrasonogram incidentally revealed a mass in the left kidney while she visited to the hospital for hypertension and unstable angina. A CT scan showed a 2 cm mass that was not clearly enhanced. MR images showed low signal intensity in both T1 and T2 images. Arteriography demonstrated no neo-vascularity. Those findings showed that this lesion was benign one or hypovascular carcinoma. So Left nephrectomy was performed and histological examination revealed a renomedullary interstitial tumor.

Roles of p53 and MDM2 in tumor proliferation and determination of the prognosis of transitional cell carcinoma of the renal pelvis and ureter.

BACKGROUND: The significance of p53 overexpression for the prognosis of transitional cell carcinoma (TCC) of the renal pelvis and ureter remains controversial. Simultaneous evaluation of p53 and MDM2 may enable better prediction of tumor proliferation and patient prognosis than that obtained with evaluation of p53 alone. METHODS: Immunohistochemical detection of p53 protein, MDM2 protein and Ki-67 antigen as proliferation markers was performed for tissue samples obtained from 74 patients with TCC of the renal pelvis and ureter. The correlations of p53/MDM2 overexpression with conventional pathological features, Ki-67 labelling index (LI) and patient survival were studied. RESULTS: Overexpression of p53 was related to progression of each of the pathological features examined (grade, stage, type of infiltration, vascular invasion and lymphatic invasion) and Ki-67 LI was significantly higher with high p53 expression than with low p53 expression. However, overexpression of MDM2 was related to neither disease progression nor Ki-67 LI. Survival analyses were performed for 66 patients. Univariate analysis showed p53 to be a useful prognostic indicator, but in a multivariate analysis only type of infiltration and Ki-67 LI were independent survival markers, while p53 was not. Overexpression of MDM2 was unrelated to patient survival, and the combination of p53 and MDM2 for survival indication was found not to be useful. CONCLUSIONS: Overexpression of p53 is related to disease progression, increased tumor proliferation and patient survival for TCC of the renal pelvis and ureter, but the independent prognostic value of p53 did not reach statistical significance. Combined analysis of MDM2 with p53 cannot be recommended for examination of the malignant potential of TCC of the renal pelvis and ureter.

[A case of neurogenic bladder due to neuro-Behçet disease].

Behçet disease is a systemic vasculitis of unknown cause with variable clinical features. The central nervous system may also be involved in about 10% of the patients with Behçet disease. Half of them show marked central nervous system symptoms and are diagnosed as neuro-Behçet disease. Voiding symptom is seen in about 5% of the patients with neuro-Behçet disease. We report a case of neuropathic vesico-urethral dysfunction in a 39-year-old man with neuro-Behçet disease. Its radiological and urodynamic features and treatment are also presented with some discussion.

Effect of sex hormones on oxalate-synthesizing enzymes in male and female rat livers.

PURPOSE: We studied the effect of changes in sex hormones on oxalate metabolism in rats. MATERIALS AND METHODS: Adult male and female rats were administered a precursor of oxalate, and the relationship between dose and urinary oxalate was examined. Levels of sex hormones were varied in rats and glycolate oxidase (GO) and serine pyruvate aminotransferase (SPT) activities were measured under the conditions of being fed tap water or loading with 0.5% ethylene glycol. In addition, urinary oxalate excretion was evaluated. RESULTS: Ethylene glycol and glycolate increased urinary oxalate concentration in male rats dose-dependently but less in female rats. There was almost no change during glycine loading in either male or female rats. GO activity was significantly lower in intact female and gonadectomized male rats. SPT activity was slightly higher in the female than in the male controls. There were no differences in urinary oxalate excretions between male and female rats. During ethylene glycol loading, GO and SPT activities were similar to those with tap water intake. However, urinary oxalate excretion increased to two times the control value in male rats but only slightly increased in female rats. CONCLUSIONS: Sex-related differences exist in the metabolic conversion of glycolate to oxalate in rats, and GO activity is promoted by testosterone. Although difference in GO activity has no physiological effect on oxalate synthesis, GO activity affects urinary oxalate excretion during ethylene glycol loading. We could also conclude that estrogen decreases GO activity in male rats from our results.

Neuropathic bladder dysfunction in patients with ossification of the posterior longitudinal ligament.

BACKGROUND: Ossification of the posterior longitudinal ligament (OPLL) may cause neuropathic bladder dysfunction due to spinal cord involvement. OPLL, unlike a traumatic spinal cord lesion, progresses insidiously and sometimes affects longer cord segments. As the manifestation of bladder dysfunction may depend on the development of OPLL, we studied the relationship between bladder function and roentgenographic changes in the spinal canals of OPLL patients. PATIENTS AND METHODS: Eighteen surgical candidates (11 males and 7 females, 34 to 85 years old) were studied urodynamically. Sixteen underwent CO2-filling cystometry, uroflowmetry and measurement of their residual urine volume. Cystometry was omitted in the remaining 2 patients. The vertical extent of OPLL and the degree of stenosis in the spinal canal was estimated by x-ray films and CT. RESULTS: The cystometric study revealed detrusor hyperreflexia in 2 patients and areflexic or underactive detrusors in 5 patients. Intermittent flows or considerable amounts of residual urine were also observed in the arefilexia/underactive group. Uroflowmetry showed a normal flow with little residual urine in both patients in whom cystometry was omitted. Bladder sensation was maintained in all patients. The occurrence of abnormal detrusor activity had no relationship to the degree of canal stenosis, while the occurrence of an areflexic or underactive detrusor correlated with the vertical extent of OPLL. CONCLUSION: Although detrusor hyperreflexia is common in an upper spinal cord lesion, attention should also be paid to the development of detrusor underactivity in patients with a wide vertical extent of OPLL.

[A case of accessory spleen presenting as retroperitoneal tumor].

We report the 13th case of accessory spleen in the retroperitoneum in the world literature. A 53-year-old man visited our hospital complaining of lassitude. Laboratory studies revealed significant anemia. Several imaging studies revealed a large retroperitoneal tumor (70 x 63 x 48 mm) in the medial aspect of the lower pole of the left kidney. The tumor was supplied arterially from the first and second lumbar arteries. Since the tumor adhered tightly to the left kidney, the kidney was resected as well as the tumor. The tumor was very hemorrhagic. On histological examination, the tumor exhibited a structure typical of splenic tissue. The retroperitoneal accessory spleen is very rare, and the literature on it is reviewed here.

[A study of the differences between the sexes in epidemiology of urolithiasis].

PURPOSE: Uroithiasis seems to be the dominant disease for male. In the recent Japanese epidemiological report, the sexual ratio was reported 2.3:1. This sexual ratio is almost stable from 1960. We studied epidemiologically based on age and stone components the differences between the sexes. PATIENTS AND METHOD: From 1977 to 1996 the upper urinary tract stones which spontaneous excretion or surgical removal in our hospital were the subjects of study, Stone analysis was carried out infrared spectrometer. The statistical analyses were performed by the chi-square test and Mann-Whitney's U test. Significance was declared for a probability value of less than 0.05. RESULTS: In the epidemiology of our treated patients sexual ratio was 1.83:1. We studied sexual ration in age and stone components. The sexual ratio of the patients, 60 years and over was decreased compared with that of the patients under 60 years of age. We found the tendency that the sexual ratio was decreased at 60 years old and over. In the female urolithiasis patients less than 60 years old the frequency of calcium oxalate contained stone patients was predominantly smaller than male. In the female urolithiasis patients of 60 years and over the stone component ratio was similar to male urolithiasis patients. CONCLUSION: In point of frequency sexual ratio was decreased at 60 years old and over. In the female patients less than 60 years old the frequency of calcium oxalate contained stone was predominantly small. This low frequency of calcium oxalate contained stone in the female less than 60 years old seemed to be a factor of the sex differences of frequency.

Pelvic nerve grafts restore bladder function in denervated rats.

BACKGROUND: Autonomic nerve preservation techniques for use during surgery for rectal cancer have improved. Nevertheless, in some patients pelvic nerves must be sacrificed to excise all tumor. For these patients, nerve reconstruction at the time of operation by using nerve grafting would be useful. A rat model of this type of nerve reconstruction is described. METHODS: Animals were divided into three groups. In the sham control group, a pelvic exploration was conducted without division of the pelvic nerves. In the nerve ablation group, both pelvic nerves were excised segmentally. In the graft group, both pelvic nerves were excised and genitofemoral nerves were interposed bilaterally. At 2-week intervals postoperatively, animals from each group underwent cystometry under urethane anesthesia and neuronal tracing using fragment C of tetanus toxin for demonstration of axonal transport via regenerated nerves. RESULTS: At 6 weeks postoperatively, 60% of the grafted animals produced rhythmic contractions of the bladder. In neuronal tracing studies at weeks 4 and 6, respectively, 40% and 100% of the nerve-grafted rats had labeled neurons in the sacral parasympathetic nucleus. CONCLUSIONS: These findings suggest that pelvic nerve grafting in rats can successfully restore bladder function after surgical injury. Clinical use of pelvic nerve grafting may be indicated for patients whose pelvic nerves must be sacrificed to excise all tumor.

[A clinicopathological study on carcinoma of the renal pelvis and ureter].

We investigated the clinicopathological features of 62 patients with transitional cell carcinoma of the renal pelvis and ureter. Four patients had been treated for bladder cancer. Among 58 patients without precedent bladder cancer, 6 had coexistent bladder cancer and bladder cancer subsequently developed in 13. The 5-year cause-specific survival rate was 33% in cases with coexistent bladder cancer, 75% in those with subsequent bladder cancer and 62% in patients without association of bladder cancer. Distant metastases were found in 23 of 62 (37%) cases, the most frequent site being lymph nodes. The site of the primary tumor (renal pelvis and/or ureter) and the pathological findings such as grade, stage, type of infiltration, venous and lymphatic invasion, were significantly correlated to cause-specific survival. Multivariate analysis showed the most influential factors to be the type of infiltration and the site of the primary tumor. Therefore, patients with INF beta or gamma tumors both in the renal pelvis and ureter had a poor prognosis. However, association of bladder cancer was not related to survival.

Analysis of proliferative activity of the parathyroid glands using proliferating cell nuclear antigen in patients with hyperparathyroidism.

To elucidate the cellular proliferative kinetics of the parathyroidal gland in patients with hyperparathyroidism, we investigated the expression of proliferating cell nuclear antigen (PCNA) in parathyroidal tissues using an immunohistochemical procedure. The PCNA labeling index (LI; maximum LI, maximal stained area; average LI, evenly distributed stained area) indicating cellular proliferative activity was defined as the number of PCNA-positive cells per 1000 parathyroid cells in the region of interest. We used these indexes to compare and investigate the proliferative activity of parathyroid cells under various conditions. The specimens used for the study were 42 parathyroid glands from 21 patients with primary hyperparathyroidism (19 cases of adenoma and 2 cases of primary hyperplasia due to multiple endocrine neoplasia type 1) and 129 parathyroid glands from 32 patients with secondary hyperparathyroidism. An additional 40 parathyroid glands resected during thyroid surgery of 30 normocalcemic patients were used as normal controls. In normally functioning parathyroids, a small number of cells in the growth phase were found. In primary hyperparathyroidism, proliferative activity was highest in the adenoma followed by primary hyperplasia. In contrast, the PCNA LIs showed a low value in the normal rim of the adenoma and normal glands resected as biopsy specimens from adenoma patients. We, therefore, assumed that proliferative activity was suppressed in these cells compared with that in normally functioning glands. In secondary hyperparathyroidism, when the cell component of the parathyroid tissues was divided into five types, PCNA immunoreactivity was lowest in the dark chief cells. Proliferative activity in cells of the oxyphil series was the same or higher than that in the clear chief cells or vacuolated chief cells. When classified according to the structure of the parathyroid glands, cell proliferation was significantly higher in the nodular type than in the diffuse type (maximum LI, 176 +/- 231 vs. 38.3 +/- 55.7; average LI, 120 +/- 188 vs. 24.8 +/- 43.5; mean +/- SD; P < 0.001). More PCNA-immunoreactive cells were found in autotransplanted glands with recurrence than in glands resected during the initial surgery. To summarize the PCNA expression classified according to the pathological types of hyperparathyroidism, the PCNA LIs were highest in secondary hyperplasia (maximum LI, 144 +/- 212; average LI, 96.0 +/- 169) and adenoma (maximum LI, 102 +/- 81.7; average LI, 67.5 +/- 67.7), followed by primary hyperplasia (maximum LI, 25.0 +/- 25.4; average LI, 19.2 +/- 22.2) and normal glands (maximum LI, 13.6 +/- 23.9; average LI, 4.40 +/- 8.90). These findings suggest that the cellular proliferative kinetics of the parathyroid gland differ depending on the type of hyperparathyroidism, glandular structure, and cell components. As the detection method of intranuclear expression of PCNA in cells is too sensitive, we should be careful not to overestimate the number of cells in the proliferative cycle. However, these results could not have been obtained using a conventional method such as DNA analysis by flow cytometry.

[Transurethral microwave thermotherapy for benign prostatic hyperplasia].

BACKGROUND: We studied the clinical efficacy of transurethral microwave thermotherapy (TUMT) using Endotherm UMW system (OLYMPUS). METHODS: TUMT was performed in 28 patients with benign prostatic hyperplasia (BPH). Three patients of them were catheterized because of urinary retention. The treatment was performed in a single session for an hour. The urethral surface temperature was set at 39 degrees C, and the coolant flow of the urethral applicator (21 Fr balloon catheter) was set at 30 ml/min, to heat up the broad area of the prostate up to 45 degrees C. The clinical efficacy was evaluated by analyzing subjective responses, using the International Prostate Symptom Score (I-PSS) scale (S) and QOL score (L), and objective responses, using peak urinary flow rate (Qmax), average flow rate (Qave), residual urine volume and prostate volume following the treatment. RESULTS: At 24 weeks after the treatment, significant improvement were observed in S score (41%), L score (37%), Qmax (53%) and Qave (62%). Although there was no significant decrease in residual urine and prostate volume. The three patients, with a catheter indwelled because of urinary retention, were all free of the catheter within 4 weeks after the treatment. During and after the treatment, no severe adverse effects, including transient urinary retention needed for indwelling a catheter, was detected. CONCLUSION: A single session of TUMT by Endotherm UMW considered to be safe and useful for symptomatic BPH patients, even who are not indicated for transurethral resection of the prostate (TUR-P) because of underlying disorders.

[Overexpression of c-erbB-2 and p53 oncoprotein in renal pelvic and ureteral carcinomas with reference to the expression of Ki-67 antigen as a proliferation marker].

PURPOSE: We determine the significance of c-erbB-2 and p53 gene in the progression of renal pelvic and ureteral carcinomas. METHODS: Overexpression of c-erbB-2 and p53 oncoprotein was investigated using immunohistochemical staining with reference to pathological features. The expression of Ki-67 antigen was also studied as a proliferation marker. RESULTS: Forty-seven cases were examined, and the overexpression of c-erbB-2 oncoprotein was revealed in 25 (53%) cases. It was not related both tumor grade (G) and tumor stage (pT). The overexpression of p53 oncoprotein was revealed in 29 (62%) cases. There were 13 p53 positive cases in 27 low grade (G1, G2) tumors, and 16 in 20 high grade (G3) tumors. There were also 8 p53 positive cases in 21 low stage (pTa, pT1) tumors, and 21 in 26 high stage (pT2-4) tumors. Thus, p53 oncoprotein was more frequently overexpressed in high grade tumors (p < 0.05) and in high stage tumors (p < 0.01). Ki-67 labelling index (LI, mean +/- SD) was 10.7 +/- 8.9 in low grade tumors and 26.3 +/- 12.5 in high grade tumors. It was also 9.0 +/- 8.1 in low stage tumors and 24.0 +/- 12.4 in high stage tumors. Thus, Ki-67 LI was higher in high grade tumors (p < 0.01) and in high stage tumors (p < 0.01). The c-erbB-2 status and Ki-67 LI were not correlated, while the LI of p53 positive cases (21. 7 +/- 13.6) was significantly higher (p < 0.01) than it of p53 negative cases (10.3 +/- 8.5). The difference of LI between p53 positive cases and p53 negative cases was significant (p < 0.05) in low grade tumors, but in high grade tumors LI was higher than it of low grade tumors independently of p53 expression. CONCLUSION: p53 but not c-erbB-2 was considered to be associated with rapid tumor progression in renal pelvic and ureteral carcinoma and play an important role in its progression especially in low grade tumors.