KIT expression in chromophobe renal cell carcinoma: comparative immunohistochemical analysis of KIT expression in different renal cell neoplasms

The overexpression of c-Kit in chromophobe renal cell carcinoma (ChRCC) has been described by comparative gene expression analyses and has been proposed as a possible specific hallmark of this neoplasm. The aim of our study was to establish its immunohistochemical expression in a large series of ChRCC and to compare it with other renal neoplasms. In our study, immunohistochemical characterization of KIT was performed in 87 renal neoplasms including 25 cases of ChRCC, 13 cases of renal oncocytoma, and 39 renal cell carcinomas (21 cases of conventional RCC [CRCC], 8 cases of CRCC with granular cell differentiation, and 10 cases of papillary RCC [PRCC]). Eighty-eight percent ChRCC and 71% oncocytomas showed immunohistochemical expression of KIT, while the other types of RCC studied were all negative. The meaning of immunohistochemical expression of KIT in ChRCC and oncocytomas is still unknown, but its immunohistochemical staining appears to be useful in distinguishing ChRCC from PRCC, CRCC, and its granular cell variant. Moreover, our findings support current models that consider that there is a histopathogenic relationship between oncocytoma and ChRCC. Finally, it should be determined whether KIT plays a role in the tumorigenesis of ChRCC and oncocytoma and whether targeted therapy with STI-571, an inhibitor of KIT, could be effective in exceptional cases of ChRCC with metastatic extension or recurrence.     

Increasing expression of extracellular matrix metalloprotease inducer in renal cell carcinoma: Tissue microarray analysis of immunostaining score with clinicopathological parameters

AIM: Renal tumor cell invasion is responsible for both local tissue destruction and distant metastasis. Invasion is largely mediated by matrix metalloproteases that are thought to be induced by tumor cell-derived extracellular matrix metalloprotease inducer (EMMPRIN) in surrounding fibroblasts. We hypothesized that EMMPRIN and matrix metalloproteinase-9 (MMP-9) are over-expressed in renal cell carcinoma. METHODS: Immunohistochemical analysis of EMMPRIN and MMP-9 was performed in tissue microarrays of 79 renal cell carcinomas including 12 cases of chromophobe renal cell carcinoma (ChRCC), 53 cases of clear cell renal cell carcinoma (CRCC), 8 cases of papillary renal cell carcinoma (PRCC), and 6 cases of carcinoma of the collecting ducts of Bellini (CoRCC). RESULTS: All renal cell carcinomas showed significant immunohistochemical expression of EMMPRIN. The EMMPRIN score in ChRCC (321+/-21) was significantly higher than in other histological subtypes of RCC (166+/-19 for CRCC; 276+/-24 for PRCC; 98+/-17 for CoRCC). MMP-9 was mainly expressed in tumor stromal cells and not in non-cancerous fibrovascular regions. The percent positive staining of MMP-9 at the invasive front of tumor cells was significantly higher in CRCC than in ChRCC, PRCC, or CoRCC. Higher EMMPRIN scores in CRCC were associated with shorter survival time, and correlated with higher T staging and nuclear grading. CONCLUSIONS: Our findings demonstrate for the first time that EMMPRIN is over-expressed in renal cell carcinomas. Increased expression of EMMPRIN in tumor cells is associated with poor prognosis of patients with CRCC.     

The value of real-time contrast-enhanced ultrasound combined with CT enhancement in the differentiation of subtypes of renal cell carcinoma

AimThis study aimed to evaluate the value of real-time contrast-enhanced ultrasound (CEUS) combined with contrast-enhanced computed tomography (CECT) in the differential diagnosis of clear cell renal cell carcinoma (CCRCC), papillary renal cell carcinoma (PRCC), and chromophobe renal cell carcinoma (CRCC).Materials and methodsIn the present study, 82 patients with CCRCC, 24 patients with PRCC, and 19 patients with CRCC were confirmed by pathology of the resected tumor. All patients were evaluated by CEUS and CECT before the operation. In addition, the contrast enhancement mode of CEUS and CECT and the contrast parameters of the region of interest (ROI) time-intensity curve between the lesions and the surrounding normal renal parenchyma by CEUS were compared and analyzed.ResultsCompared with the pathological results, the diagnostic accuracy of ultrasound in the 3 groups was 87.8% (72/82), 83.3% (20/24) and 73.7% (14/19). There was no significant difference between CEUS and CECT in the diagnostic accuracy of all groups (P>0.05). Meanwhile, compared with the surrounding renal parenchyma by CEUS, 82.5% (66/80) of CCRCC lesions showed “fast-forward and fast/slow-retrograde,” while 83.3% (20/24) of PRCC, and 84.2% (16/19) showed “slow-forward and fast/slow-retrograde.” Significant differences in the enhancement modes of CEUS were found among the CCRCC, PRCC, and CRCC lesions (P < 0.05). And the enhancement modes could be quantitatively analyzed by the ROI time-intensity curve of the lesion. Moreover, lesions enhanced by CECT and 74.4% (61/82) of CCRCC lesions showed “fast-forward and fast/slow-retrograde,” while 66.7% (16/24) of PRCC and 84.2% (16/19) of CRCC showed “slow-forward and fast/slow-retrograde.” The contrast modes and enhancement uniformity of CEUS and CECT showed no significant differences among the CCRCC, PRCC, and CRCC lesions (P > 0.05).ConclusionCEUS and quantitative analysis of ROI time-intensity curve can be used for differential diagnosis of the 3 RCC subtypes. The combination of CEUS and CECT can help us differentiate RCC subtypes and is of great significance for clinical treatment strategies and prognostication.     

Association of EMMPRIN and fascin expression in renal cell carcinoma: correlation with clinicopathological parameters

EMMPRIN and fascin are important factors in tumor invasion and progression. We tested the hypothesis that expression of EMMPRIN and fascin correlate with clinicopathological parameters of renal cell carcinoma (RCC). Immunohistochemical analysis of EMMPRIN and fascin were performed in tissue microarrays of 100 surgical specimens, including 35 clear-cell RCC (CRCC), 21 clear-cell RCC with granular differentiation (GRCC), 12 chromophobe RCC (ChRCC), 8 papillary RCC (PRCC), 9 carcinoma of the collecting duct of Bellini (CDC), 10 clear-cell RCC with sarcomatoid differentiation (SRCC), and 6 metastatic RCC. Average immunoscores of EMMPRIN were 100.8 in CRCC, 195.2 in GRCC, 298.4 in ChRCC, 219.2 in PRCC, 186.1 in CDC, 226.9 in SRCC, and 151.7 in metastatic RCC. Among all included cases, average EMMPRIN immunoscores were 84.6 in grade I, 130.4 in grade II, 184.3 in grade III, and 223.5 in grade IV. Additionally, average immunostaining scores of fascin were 53.6 in CRCC, 289.3 in GRCC, 193.3 in ChRCC, 151.8 in PRCC, 181.3 in CDC, 275.4 in SRCC, and 131.7 in metastatic RCC. Average fascin immunoscores were 59.3 in grade I, 91.6 in grade II, 130.2 in grade III, and 194.7 in grade IV. Higher EMMPRIN and fascin immunoscores also correlated significantly with TNM stages and survival rates in RCC. Significant correlation was found between EMMPRIN and fascin expression. In conclusion, higher expression of EMMPRIN and fascin correlate significantly with histological grades, clinical stages, and survival rates of RCC     

Cyst-associated renal cell carcinoma: Clinicopathologic characteristics and evaluation of prognosis in 27 cases

BACKGROUND: No consistent clinicopathologic characteristics of cyst-associated renal cell carcinoma (CRCC) have previously been determined. METHODS: In total, 768 patients with renal cell carcinoma (RCC) underwent radical or partial nephrectomy. Renal cell carcinoma was classified as CRCC in 27 of these patients (3.5%, subdivided into RCC originating in a cyst and cystic RCC), clear-cell RCC in 662 patients (86.2%), chromophobe cell renal carcinoma in 36 patients (4.7%) and papillary RCC in 43 patients (5.6%) according to the criteria of the World Health Organization. RESULTS: The pathologic stage and nuclear grade were usually lower in those with CRCC (low stage/low grade; 89%/96%) or chromophobe cell renal carcinoma (low stage/low grade; 89%/80%) than in those with clear-cell RCC (low stage/low grade; 59%/65%) or papillary RCC (low stage/low grade; 53%/69%). Of the 27 CRCC patients, only 19 (70%) could be diagnosed through preoperative imaging studies. Patients with CRCC showed a favorable prognosis (survival rate: 95% at 1 year, 89.7% at 3 years and 84.4% thereafter) and, especially among the patients with RCC originating in a cyst, no cancer-related death was observed. Comparing the survival among four types of RCC, a favorable outcome was observed in cases of CRCC or chromophobe cell renal carcinoma compared with clear-cell RCC or papillary RCC (clear vs chromophobe: P = 0.002; chromophobe vs papillary: P = 0.019; clear vs cyst-associated: P = 0.001; papillary vs cyst-associated: P = 0.00079). CONCLUSIONS: In cases of CRCC, the disease was usually detected at lower stages and grades and therefore the prognosis was better than in cases of other types of RCC. Preoperative diagnosis of this disease was very difficult, especially in cases of RCC originating in a cyst.     

Renal tumour size measured radiologically before surgery is an unreliable variable for predicting histopathological features: benign tumours are not necessarily small

OBJECTIVE: To compare histopathological findings as a function of radiological tumour size, as published data suggest that small renal tumours are often benign and large tumours are renal cell cancer (RCC). PATIENTS AND METHODS: Data from 543 surgically treated patients with solid renal tumours were analysed retrospectively. Tumour size measured by computed tomography (CT) before surgery was stratified into seven subgroups (cm): 0-2, 2.1-3, 3.1-4, 4.1-5, 5.1-6, 6.1-7 and >7, and correlated with final histology. RESULTS: In all, 80 lesions (14.7%) were benign on final histology; tumour size did not correlate with benign histology (P=0.660). Histopathological tumour size was not statistically significant different (P=0.521) from measured tumour size on CT, and there was no statistical significance between CT and histopathological tumour size (P=0.528). Only 13 (17%) of lesions were correctly defined as benign on CT before surgery, whereas 67 (83%) were considered to be suspicious for malignant disease. Only one patient with a tumour correctly defined as benign had a radical nephrectomy; by contrast, 28 of 67 (42%) had a radical nephrectomy for benign lesions not correctly identified as benign on CT before surgery (P<0.001). CONCLUSION: Substantially many renal masses are benign, independent of tumour size. Radical nephrectomy could potentially have been avoided in 42% of patients with benign renal tumours. These data provide a good argument for the use of a more refined preoperative diagnostic evaluation, in particular needle biopsy.     

Partial nephrectomy for renal tumours: the Singapore General Hospital experience.

From January 1991 to August 1998, 220 radical nephrectomies were performed for renal cell carcinoma (RCC). During the same period, 27 patients underwent partial nephrectomy for their renal tumours. These included 19 male and 8 female (mean age, 54; range, 35-75). Their clinical presentation, diagnostic modalities and surgical outcome were evaluated. The lesions included 18 RCCs, 7 angiomyolipomas (AMLs), 1 oncocytoma and 1 dysoncogenetic renal tumour. Only 8 patients had specific urological symptoms. Computerised tomography (CT) scan was diagnostic in 78% of cases. Tumour size ranged from 15-50 mm for RCC and 30-190 mm for AML, respectively. Operative time averaged 92 minutes (range: 35-145). The hospital stay ranged from 3 to 25 days (mean 11). Complications occurred in four cases (14.8%); there was one death (3.7%). No tumour recurrence was detected during a mean follow up of 20 months. None of the patients developed significant renal impairment. Partial nephrectomy is feasible in small RCC and some large AML, and can be offered in selected patients.     

Hemodialysis case in which RCC was identified after disappearance of perirenal hematoma following spontaneous renal rupture treated by transcatheter arterial embolization

A 55-year-old man who had been undergoing hemodialysis for 9 years visited our institution after the sudden onset of severe left flank pain. He presented with hypotension and was admitted immediately because computed tomography (CT) revealed a massive perirenal hematoma. Renal arteriography showed contrast media leakage at the lower branch of the left renal artery, and spontaneous renal rupture was diagnosed. Five months after the bleeding was stopped by selective transcatheter embolization of the branch of renal artery, CT showed an enhanced mass at the upper pole of left kidney and renal cell carcinoma (RCC) was suspected. Radical nephrectomy was performed, the pathological diagnosis was clear cell carcinoma, and the man has not experienced recurrence within 36 months after the surgery. RCC did not appear to be the cause of the original hemorrhage because there was a small residual hematoma in the middle of the renal parenchyma that was separated from the RCC. In cases of spontaneous renal rupture, re-evaluation by imaging studies is mandatory after disappearance of perirenal hematoma because imaging studies at the time of the rupture sometimes do not reveal the cause of the hemorrhage.     

乳头状肾细胞癌的临床特征分析（附7例报告）

目的：观察乳头状肾细胞癌的临床特点,提高对其诊断要点、治疗及预后的认识。方法：回顾性分析7例乳头状肾细胞癌患者的临床资料,复习相关文献,并对患者进行随访。结果：7例患者均经病理证实为乳头状肾细胞癌,1例并发肾上腺腺瘤;首发症状主要以腰痛、血尿、消瘦、低热为主;CT影像均提示肿瘤密度在肾髓质期强化程度明显弱于肾皮质,且在肾髓质期和排泄期呈均匀强化;6例经腹行根治性肾切除,1例经腰行根治性肾切除,术后均辅以免疫治疗,未行放化疗;6例获随访,随访时间为3个月～2年,1例于术后6个月出现急性肾衰死亡,1例于12个月因肝及淋巴结转移死亡,其余4例在随访期间未出现复发和转移,无瘤生存至今。结论：乳头状肾细胞癌与其它肾细胞癌在临床表现上基本相同,但在影像学表现,病理形态及生物学行为上均与其他类型的肾细胞癌不同,诊断主要依靠CT影像,确诊有赖于病理和免疫组织化学检查,早期手术是首选治疗方式,其预后可能与分期及转移有关。     

Tumours in End-Stage Kidney

Objective

Patients with end-stage kidney disease (ESKD) show a greater risk for renal cell carcinoma (RCC), which tends to be multifocal and bilateral. The malignant potential is unclear. The question is whether to remove both kidneys in patients with a tumor on one side only diagnosed by computed tomography (CT).

Materials and Methods

Kidney tumors were found in 14 patients with ESKD from January 2002 to December 2006. One was unfit for surgery. Thirteen patients underwent nephrectomy and 6 a bilateral procedure of whom only 2 had bilateral tumors on CT, 3 multiple tumors on the contralateral side, and 1 uncontrollable hypertension with tumors as an incidental finding. Tumors were found in all 19 specimens.

Results

In 13 kidneys (68.4%), the tumors were multiple; in 6 (31.6%), solitary. The types of tumor were: 13 (68.4%) papillary RCCs (PRCC), 9 (47.4%) clear RCCs (CRCC), a combination of PRCC and CRCC in 4 (21.0%), and myxoid liposarcoma (with solitary PRCC contralaterally). The mean follow-up was short (19 ± 15 months; maximum, 54 months). Only 1 patient died due to a tumor at 16 months after operation.

Conclusions

There is a high risk for bilateral involvement. Patients who undergo unilateral nephrectomy must be regularly followed and contralateral nephrectomy carefully considered, mainly in transplanted patients on immunosuppression. Further studies are needed to give a definitive answer about the indications for surgery and the indications for contralateral nephrectomy as well. To date, prophylactic contralateral nephrectomy should not be a therapeutic standard.     

Expression of cortactin and survivin in renal cell carcinoma associated with tumor aggressiveness

Purpose  We tested the hypothesis that the expression of cortactin and survivin in renal cell carcinomas (RCCs) correlates with more advanced stages of the disease. Methods  Immunohistochemical analysis of cortactin and survivin expression (scored on a scale of 0–400) was performed in 124 renal cell carcinomas including clear cell renal cell carcinoma (CRCC), papillary RCC (PRCC), CRCC with sarcomatoid differentiation (SRCC), chromophobe RCC (ChRCC), and CRCC with granular cell differentiation (GRCC). Results  Higher cortactin scores in CRCC were significantly correlated with higher T (p = 0.021) and N stages (p = 0.036), and nuclear grade (p = 0.012). Higher cortactin immunostaining scores were associated with higher mortality (p = 0.035). In addition, the survivin scores were significantly higher in the more aggressive GRCC and SRCC than in CRCC, suggesting a significant role of survivin expression in transformation of tumor cells to a more malignant phenotype. Conclusions  Higher expression of cortactin and survivin significantly correlated with advanced clinicopathological stage. Our findings support the potential targeting of survivin and cortactin for the development of novel therapeutic strategies for renal cell carcinoma.     

Hybrid tumour ‘oncocytoma‐chromophobe renal cell carcinoma’ of the kidney: a report of seven sporadic cases

OBJECTIVES

To determine whether renal hybrid tumours (HT) appear as a specific clinical and radiological entity, as HT are characterized by the association of both oncocytes and chromophobe cells within the same tumour, and have been described in patients with oncocytosis and Birt‐Hogg‐Dube syndrome.

PATIENTS AND METHODS

We reviewed the medical charts of 67 patients who had a partial or radical nephrectomy in our institution for renal oncocytoma (RO, 24), chromophobe renal cell carcinoma (CRCC, 36) and HT (seven), from January 2006 to October 2007. We report the clinical, radiological and pathological characteristics of the seven cases of HT.

RESULTS

The mean (range) age of the patients was 56 (41–68) year. None of the seven patients had any suspicion of RO, based on computed tomography (CT). Two patients had a history of kidney cancer. Five patients had partial and two a radical nephrectomy. The mean (range) maximum tumour diameter was 5.5 (1.8–9) cm. Two tumours were pT1a, two were pT1b and three were pT2. Pathological analysis showed RO‐like and CRCC‐like cells intermixed (six patients) or distinct (one). After a median (range) follow‐up of 20 (8–25) months, none of the patients had any evidence of disease recurrence.

CONCLUSIONS

In a large series of patients with sporadic RO and CRCC, 10% of the tumours had hybrid morphological features, as described in oncocytosis and Birt‐Hogg‐Dube syndrome. We were unable to identify any specific clinical characteristic. Most importantly, none of these HT showed any of the radiological characteristics of RO.     

Computerized contrast angiosonography: a new diagnostic tool for the urologist?

OBJECTIVES: To evaluate the diagnostic potential of echo-enhanced ultrasonography (US) for depicting the vascularization pattern of renal cell carcinoma (RCC), and calculating the first-pass effect using harmonic imaging, against that obtained by triphasic helical computed tomography (CT). PATIENTS AND METHODS: Sixty patients with surgically confirmed RCC underwent US using B-mode and power Doppler methods with or without an intravenous microbubble echo-enhancing agent. After depicting and defining the tumour extent by B-mode US, the first-pass effect/enhancement by the echo-enhancing agent within the lesion, and that of a reference area of unaffected renal cortex, were recorded on-line by calculating the mean pixel intensity. Time-intensity curves, i.e. the rise time and gradient of both the suspected tumour and reference areas, were constructed. RESULTS: Using B-mode US, the extent of all tumours was delineated (mean tumour size 3.8 cm, SD 0.6). After applying the microbubble agent all tumours were enhanced, whereas the perfusion was decreased (in 48%), increased (in 16%) or similar (in 36%) compared with the cortical reference area. Using the Hounsfield classification, these results correlated well with the hypo/hypervascularity shown on CT. CONCLUSION: Ultrasonography has considerable potential in diagnosing RCC, if combined with echo-enhancing methods, harmonic imaging and computer-based calculation of tumour vascularization. Dynamic US studies should provide a diagnostic yield similar to that of CT.     

Tubulocystic renal carcinoma: a clinical perspective

Introduction

Tubulocystic renal carcinoma (TCRC) is a recently described neoplastic entity. To date, clinicopathological features on less than hundred cases of these rare tumours have been characterized exclusively in the pathological literature. Herein, we present five additional cases emphasizing clinical aspects on these rare renal neoplasms.

Material and method

Cases diagnosed as TCRC were retrieved and reviewed from the routine and consultation files of the Pilsen tumour registry comprising over 20,000 cases of renal tumours.

Results

All patients were men, mean age 56 years (range 29–70). Features on computed tomography (CT) were in two cases Bosniak III, one IV and two were solid tumours. In four patients, nephrectomy was performed, and one patient underwent resection. At the time of surgery, two patients had metastases. In one case, both primary tumour and metastases were active on FDG positron emission tomography (PET)/CT. Both patients with metastatic disease were treated with sunitinib with partial response. One patient died 26 months postoperatively and the other patient is alive 5 months after surgery. Three patients with localized tumours are without evidence of disease 31, 28 and 7 months after surgery. In one case, the resected tumour was histologically combined with a papillary renal cell carcinoma (PRCC).

Conclusion

TCRC occurs predominantly in men with a wide age range. TCRC frequently displays a cystic component which may render a radiological classification of Bosniak III or IV. FDG PET/CT is helpful in the detection of metastases. TCRC has definitive malignant potential. Our findings support a possible relationship to PRCC. The tyrosine kinase inhibitor sunitinib may be used a therapeutical agent with partial response and temporary effect.     

Spontaneous rupture of renal cell carcinoma: a case report

A 45-year-old man felt sudden pain in the left abdomen while taking a bath. Computed tomography (CT) showed a huge hematoma above the left kidney, which was diagnosed as spontaneous rupture of the kidney. Two months later, several low-density areas were observed in the liver on CT. Suspecting renal cell carcinoma (RCC) with multiple liver metastasis, we performed left radical nephrectomy and partial hepatectomy. A pathological study revealed a small RCC of 2 cm in diameter in the middle of the left kidney. In spontaneous renal rupture secondary to renal tumors, imaging studies such as CT or MRI sometimes fail to demonstrate primary lesions.     

Genetic identification of bilateral primary or metastatic nonpapillary renal cell carcinoma

OBJECTIVE: To clarify the clonality of bilateral tumours by genetic analysis of bilateral renal cell carcinomas (RCCs) using the VHL gene, which is inactivated in approximately 60% of RCCs and which plays a causal role in the development of most cases of nonpapillary RCC. PATIENTS AND METHODS: The study included 20 patients; seven had von Hippel-Lindau disease, three had papillary RCC and 10 had nonpapillary RCC. Paraffin-embedded blocks of tumour tissue were obtained from two of the three patients with papillary RCC and from nine of 10 with nonpapillary disease; all three exons of VHL were examined by direct sequencing. RESULTS: As reported previously, no VHL mutations were found in papillary tumours. However, in five of the nine nonpapillary cases, VHL mutations were identified in tumours on one or both sides. Three of the tumours had the same mutation on both sides, confirming a common origin. In the remaining two patients, the mutation status differed between the sides, confirming a bilateral primary origin. The former cases were characterized by a relatively large tumour on one side and multiple tumours on the other. CONCLUSIONS: In nonpapillary RCC multiplicity may suggest a metastatic origin. Such genetic information will be useful in treating and following patients with bilateral renal tumours.     

肾错构瘤自发性破裂出血的外科诊治(附5例报告)

目的:探讨肾错构瘤破裂出血的诊断和治疗方法。方法:回顾性分析2003年7月～2007年3月收治的5例肾错构瘤破裂出血患者的临床资料,4例急诊行手术治疗,1例行保守治疗后1周行手术治疗。手术方式均选择患肾切除术。结果:5例术后恢复良好,术后病理检查报告为肾错构瘤,无恶变。结论:B超和CT检查对诊断肾错构瘤破裂出血有帮助。肾错构瘤的治疗应全面考虑,手术仍为主要的治疗方法。     

A case of cystic renal cell carcinoma: clinical usefulness of CT arteriography

We report a case of cystic renal cell carcinoma (CRCC). In general, computed tomography (CT) and magnetic resonance imaging (MRI) are sufficient for diagnosing renal cell carcinoma (RCC). However, we often have difficulty in diagnosing CRCC based on these modalities alone. In the present case, to assess the contrast-enhancement of the cyst wall and the septum, we evaluated the usefulness of CT arteriography (CTA) by selective injection of contrast material into the renal artery. We believe that CTA could be a valid option for preoperative radiological differentiation of CRCC.     

Unclassified renal cell carcinoma: an analysis of 85 cases

OBJECTIVES: To compare cancer-specific mortality in patients with unclassified renal cell carcinoma (URCC) vs clear cell RCC (CRCC) after nephrectomy, as URCC is a rare but very aggressive histological subtype. PATIENTS AND METHODS: Eighty-five patients with URCC and 4322 with CRCC were identified within 6530 patients treated with either radical or partial nephrectomy at 18 institutions. Of 85 patients with URCC, 55 were matched with 166 of 4322 for grade, tumour size, and Tumour, Node and Metastasis stages. Kaplan-Meier and life-table analyses were used to address RCC-specific survival. Subsequently, multivariate Cox regression analyses were used to test for differences in RCC-specific survival in unmatched samples. RESULTS: Of patients with URCC, 80% had Fuhrman grades III or IV, vs 37.8% for CRCC. Moreover, 36.5% of patients with URCC had pathologically confirmed nodal metastases, vs 8.6% with CRCC. Finally, 54.1% of patients with URCC had distant metastases at the time of nephrectomy, vs 16.8% with CRCC. Despite these differences in the overall analyses, after matching for tumour characteristics, the URCC-specific mortality rate was 1.6 times higher (P = 0.04) in matched analyses and 1.7 times higher (P = 0.001) in multivariate analyses. CONCLUSIONS: These findings indicate that URCC presents with a higher stage and grade, and even after controlling for the stage and grade differences, predisposes patients to 1.6-1.7 times the mortality of CRCC.