Histological Subtypes Of Renal Cell Carcinoma Research Articles

Renal Cell Carcinoma Fuhrman Grade and Histological Subtype Correlate With Complete Polymorphic Deletion of Glutathione S-Transferase M1 Gene

We outlined the putative significance of GST in renal cell carcinoma biology by investigating the influence of its deletion polymorphisms on renal cell carcinoma progression. Genomic DNA was purified from peripheral blood leukocytes. GSTM1 and GSTT1 genes were polymerase chain reaction amplified and gene fragments were separated by agarose gel electrophoresis. Intact GSTM1 and GSTT1 alleles were identified by the presence of 230 and 480 bp fragments, respectively. Genotypes were associated with clinicopathological variables and survival. Of 147 patients with renal cell carcinoma 80 (54%) had the GSTM1 null and 27 (18%) had the GSTT1 null genotype. The GST genotype distribution did not differ significantly from that in 112 controls without renal cell carcinoma. However, the GSTM1 null genotype was associated with 60% lower odds of the papillary subtype (OR 0.40, 95% CI 0.18 to 0.92, p = 0.032), lower Fuhrman grade (chi-square 9.77, p = 0.008) and a lower risk of metastatic disease in patients with the clear cell subtype (chi-square 4.48, p = 0.034). Of patients with the clear cell subtype those with the GSTM1 null genotype had improved cancer specific survival (p = 0.0412). GSTT1 did not correlate with any pathological variable except age at renal cell carcinoma onset since patients with renal cell carcinoma and the GSTT1 null genotype were significantly younger than their counterparts (mean +/- SD age 58.5 +/- 14.2 vs 65.4 +/- 12.8 years, p = 0.016). GSTM1 deletion polymorphism impacts renal cell carcinoma histological subtype, Fuhrman grade and metastatic behavior while GSTT1 deletion leads to renal cell carcinoma onset at a younger age. In patients with clear cell renal cell carcinoma the GSTM1 null genotype may be associated with better prognosis.

Obesity is associated with a higher risk of clear‐cell renal cell carcinoma than with other histologies

To investigate the association between body mass index (BMI) and histology of renal cell carcinoma (RCC) in a contemporary cohort, as obesity is increasingly prevalent in the USA and might be contributing to the increasing incidence of RCC, but little is known about the relationship of obesity with the different histological subtypes of RCC. From January 2000 to December 2007 we identified 1640 patients with renal cortical tumours undergoing surgical extirpation at our institution, and who had their BMI recorded. Multivariable logistic regression models were used to test the association of BMI with RCC histology. The median (interquartile range) BMI was 28 (25-32) kg/m(2) and 38% of patients were classified as obese (BMI >30 kg/m(2)). After adjusting for tumour size, age, gender, American Society of Anesthesiologists score, estimated glomerular filtration rate, hypertension, diabetes mellitus and smoking, the BMI was significantly associated with clear-cell histology; the odds ratios were 1.04 for each unit of BMI (95% confidence interval, CI, 1.02-1.06; P < 0.001) and 1.48 when comparing obese vs non-obese patients (95% CI 1.19-1.84; P < 0.001). In the subgroup of patients with RCC (excluding benign renal cortical tumours), BMI was still an independent predictor of clear-cell histology (odds ratio 1.04, 95% CI 1.02-1.06, P = 0.001). These results suggest that BMI is an independent predictor of clear-cell histology in patients with a renal cortical tumour. While the aetiology of this phenomenon requires further study, these findings might have implications in determining a patient's risk of harbouring a clear-cell RCC and in subsequent treatment recommendations.

The role of surgery in clinical management of patients with metastatic papillary renal cell carcinoma

Patients with metastatic papillary renal cell carcinoma (RCC) show special clinical behavior compared to patients with other histologic subtypes of RCC. This study aimed to assess the relevance of surgical and systemic options used in treatment of these patients prior to the recent era of targeted therapies. Retrospectively, we assessed clinical data of 61 patients with metastatic papillary RCC who were treated at eight centers in Germany. Median follow-up was 20 (range 1-114) months and median age at time of diagnosis was 62 (range 24-85) years. Men were affected predominantly (50/61; 82%). Twenty-one patients (34%) showed metastases at time of diagnosis. In the remaining 40 patients, median time to development of metastases was 30.4 (range 3-143; mean 16.5) months. Sites of metastases were lung (37; 61%), bone (24; 38%), liver (20; 33%), lymph nodes (24; 38%), and local recurrence (17; 28%). Others sites of disease were brain metastases (6 patients/10%), peritoneal carcinosis (5 patients/8%), and others. A surgical approach with potentially curative intention was performed primarily in 11 patients (18%). 31 patients received an immuno- (interferon-alpha +/- interleukin-2) or immunochemotherapy as first line treatment for metastatic disease. Overall, 42/61 patients (69%) received systemic therapy. Supportive care only was performed in 12 patients (20%) because of poor performance status. Median overall survival after diagnosis of metastatic disease was longer than 48 months in patients with tumor resection (n = 11) compared to 13.0 +/- 4.3 months 95% CI 4.5-21.5 (n = 42) months in patients without surgical approach. Complete resection of metastases represents a valid option in management of patients with relapsing or metastatic papillary RCC.

MP-14.07: Role of Ethnicity and Gender on Presentation and Survival in Papillary Renal Cell Carcinoma

Numerous studies have demonstrated that African Americans (AA) have a higher incidence and mortality rates from renal cell carcinoma (RCC) as compared to other ethnic groups. However, it is unclear which RCC histological subtypes are contributing to this disparity. In this study, we evaluated the patterns of disease presentation and outcomes among both AA and Caucasians with a papillary RCC diagnosis.

Angiogenesis of renal cell carcinoma: perfusion CT findings

To observe the perfusion CT findings of renal cell carcinoma (RCC) and prospectively correlate perfusion CT parameters with tumor MVD and VEGF expression. Dynamic contrast-enhanced multislice spiral CT was performed prospectively in 73 cases with histologically proven RCC (65 clear cell, 3 papillary, and 5 chromophobe). Blood flow (BF), blood volume (BV), mean transit time (MTT), and permeability surface-area product (PS) of RCC and normal renal cortex were measured, respectively. The tumor MVD count and VEGF expression level were determined by immunohistochemistry with specific monoclonal antibodies. There was significant difference between BF, BV, MTT, and PS of normal renal cortex (454.32 ± 110.90 mL/min/100 g, 23.53 ± 5.71 mL/100 g, 3.62 ± 1.38 s, 63.95 ± 18.85 mL/min/100 g) and RCC (261.96 ± 175.86 mL/min/100 g, 17.17 ± 8.34 mL/100 g, 7.08 ± 3.42 s, 25.07 ± 13.20 mL/min/100 g) (P < 0.01). BF and BV among RCC histologic subtypes were significantly different (P < 0.05), MTT and PS were not (P > 0.05). MVD (42.29 ± 21.00) of RCC is positively correlated with BF, BV, and PS (P < 0.01), not with MTT (P > 0.05). No relationship was found between the expression levels of VEGF and any perfusion CT parameter. Perfusion CT is a feasible technique to assess tissue perfusion in patients with RCC. BV, BF, and PS correlate positively with MVD and may reflect angiogenesis of RCC.

Does Histologic Subtype Affect Oncologic Outcomes After Nephron-sparing Surgery?

To test whether renal cell carcinoma (RCC) histologic subtypes (HSs) affect cancer-specific mortality after nephron-sparing surgery (NSS). HSs are considered of prognostic value in RCC. For example, the papillary HS might confer a worse prognosis, and, at some centers, only radical nephrectomy is performed for the papillary HS. We used univariate and multivariate Cox regression models to study patients with Stage T1N0M0 RCC treated with NSS (n = 1205) from 1988 to 2004. The data were taken from 9 Surveillance, Epidemiology, and End Results registries. At 36 months after NSS, the cancer-specific mortality rate was 97.8%, 100%, and 97.4% for a clear cell, chromophobe, and papillary RCC HS, respectively. On univariate and multivariate analyses, no statistically significant differences were recorded with regard to the HS. Despite the suggested more aggressive phenotype of the papillary HS, we found no difference among the papillary, chromophobe, and clear cell variants. Thus, the diagnosis of one HS vs another HS should not deter from the use of NSS when cancer-specific mortality is considered as an endpoint.

The role of the ADC value in the characterisation of renal carcinoma by diffusion-weighted MRI

The purpose of this study is to evaluate the role of diffusion-weighted imaging (DWI) in combination with T(1) and T(2) weighted MRI for the characterisation of renal carcinoma. The institutional review board approved the study protocols and waived informed consent from all of the patients. 47 patients (32 male and 15 female; age range, 21-85 years; median age, 65 years) who had suspected renal lesions on abdominal CT underwent MRI for further evaluation and characterisation of the lesions from April 2005 to August 2007 in our university hospital. A region of interest was drawn around the tumour area on apparent diffusion coefficient (ADC) maps. Final diagnosis was confirmed by histological examination of surgical specimens from all patients. The ADC value was significantly higher in renal cell carcinoma (RCC) than in transitional cell carcinoma (2.71+/-2.35 x 10(-3) mm(2) s(-1) vs 1.61+/-0.80 x 10(-3) mm(2) s(-1); p = 0.022). While analysing the histological subtypes of RCC, a significant difference in ADC values between clear cell carcinoma and non-clear cell carcinoma was found (1.59+/-0.55 x 10(-3) mm(2) s(-1) vs 6.72+/-1.85 x 10(-3) mm(2) s(-1); p = 0.0004). Similarly, ADC values of RCC revealed a significant difference between positive and negative metastatic lesions (1.06+/-0.38 x 10(-3) mm(2) s(-1) vs 3.02+/-2.44 x 10(-3) mm(2) s(-1); p = 0.0004), whereas intensity on T(1) and T(2) weighted imaging did not reach statistical significance. In conclusion, DWI has clinical value in the characterisation of renal carcinomas and could be applied in clinical practice for their management.

Renal Lesions: Characterization with Diffusion-weighted Imaging versus Contrast-enhanced MR Imaging

To compare the diagnostic performance of diffusion-weighted (DW) magnetic resonance (MR) imaging with that of contrast material-enhanced (CE) MR imaging and to assess the performance of these examinations combined for the characterization of renal lesions, with MR follow-up and histopathologic analysis as the reference standards. The institutional review board waived the requirement of informed patient consent for this retrospective HIPAA-compliant study. One hundred nine renal lesions in 64 patients (46 men, 18 women; mean age, 60.7 years) were evaluated with CE MR imaging and breath-hold DW imaging performed with various b values. Renal lesions were characterized with use of CE MR criteria, and apparent diffusion coefficients (ADCs) were measured. The ADCs of benign and malignant lesions were compared at Mann-Whitney testing. Receiver operating characteristic (ROC) analysis was performed to assess the accuracy of DW imaging and CE MR imaging in the diagnosis of renal cell carcinoma (RCC). The 109 renal lesions--81 benign lesions and 28 RCCs--had a mean diameter of 4.2 cm +/- 2.5 (standard deviation). The mean ADC for RCCs (1.41 x 10(-3) mm(2)/sec +/- 0.61) was significantly lower (P < .0001) than that for benign lesions (2.23 x 10(-3) mm(2)/sec +/- 0.87) at DW imaging performed with b values of 0, 400, and 800 sec/mm(2). At a cutoff ADC of less than or equal to 1.92 x 10(-3) mm(2)/sec, the area under the ROC curve (AUC), sensitivity, and specificity of DW imaging for the diagnosis of RCCs (excluding angiomyolipomas) were 0.856, 86%, and 80%, respectively. The corresponding AUC, sensitivity, and specificity of CE MR imaging were 0.944, 100%, and 89%, respectively. Combined DW and CE MR imaging had 96% specificity. The AUC for the DW imaging-based diagnosis of solid RCC versus oncocytoma was 0.854. Papillary RCCs had lower ADCs than nonpapillary RCCs. DW imaging can be used to characterize renal lesions; however, compared with CE MR imaging, it is less accurate. DW imaging can be used to differentiate solid RCCs from oncocytomas and characterize the histologic subtypes of RCC.

Pathological tumour diameter predicts risk of conventional subtype in small renal cortical tumours

To examine whether pathological tumour diameter assists in predicting conventional vs other histological subtypes in renal cortical tumours (RCTs) of <or=4 cm diameter. In all, 393 patients from Columbia University's Comprehensive Urologic Oncology Database who underwent radical or partial nephrectomy between 1988 and 2005 and had RCTs of <or=4 cm were analysed. Logistic regression analysis using tumour diameter as a continuous variable was used to determine whether size predicted histological subtype. Odds ratios (ORs) were calculated to estimate the likelihood of having conventional histology based on diameter. The median patient age at surgery was 64.3 years and median tumour diameter was 3 cm, In all, 256 (65.1%) of the RCTs were conventional subtype and 137 (34.9%) were nonconventional. Logistic regression analysis showed that for every 1 cm increase in diameter up to 4 cm, the RCT was 1.27 times more likely to be conventional (P = 0.020). The ORs showed that a 4-cm RCT was 2.06 times more likely to be conventional than tumours of 0.6-1.5 cm. There was a positive association between RCT diameter and the risk of having conventional renal cell carcinoma (RCC). Given that RCC histological subtype is a prognostic indicator for outcome, these findings may be applied in the selection of treatment options. Further studies investigating tumour size and other variables predictive of tumour histology will help clinicians better predict the RCC subtype.

Differences in Organ System of Distant Metastasis by Renal Cell Carcinoma Subtype

The majority of the published data regarding the rates of renal cell carcinoma metastasis to specific locations has examined renal cell carcinoma as a whole. We evaluated site of distant metastasis by renal cell carcinoma histological subtype. We studied 910 patients treated with radical nephrectomy for clear cell, papillary or chromophobe renal cell carcinoma at the Mayo Clinic between 1970 and 2000 who had distant metastasis at nephrectomy or who had metastasis during followup. The sites of metastases were compared by histological subtype using the chi-square and Fisher exact tests. There were 853 (94%) patients with clear cell, 39 (4%) with papillary and 18 (2%) with chromophobe renal cell carcinoma. Median followup for the 65 patients who were still alive at last followup was 11.6 years. Patients with clear cell renal cell carcinoma were more likely to have metastasis to the lungs (53.6%) compared to those with papillary (33.3%) and chromophobe (33.3%) renal cell carcinoma (p = 0.012). Patients with chromophobe renal cell carcinoma were more likely to have metastasis to the liver compared to those with clear cell renal cell carcinoma (33.3% vs 9.7%, p = 0.007), but there was not a statistically significantly difference in the incidence of liver metastases between patients with chromophobe and papillary renal cell carcinoma (33.3% vs 18.0%, p = 0.308). Site of distant metastasis varies significantly by renal cell carcinoma histological subtype. Patients with clear cell renal cell carcinoma are more likely to have metastasis to the lungs while patients with chromophobe renal cell carcinoma are more likely to experience liver metastasis.

Small Renal Tumors: Correlation of Clinical and Pathological Features With Tumor Size

We analyzed the association between tumor diameter and pathological stage, histological subtype, tumor grade and the incidence of metastases in renal cell carcinoma with a diameter of up to 4 cm (clinical stage T1a). We analyzed a consecutive series of 663 patients with renal tumors 4 cm or less who underwent surgery at our institution between 1990 and 2006. After excluding 115 patients (17.3%) with benign tumors 548 with renal cell carcinoma were included in the study. Tumor size on preoperative imaging was correlated with pathological stage, tumor grade, histological subtype and incidence of metastases at diagnosis. For data analysis tumors were stratified by tumor diameter into 3 groups, including 2 cm--99 patients with tumors up to 2 cm, 3 cm--234 with tumors between 2.1 and 3.0 cm, and 4 cm--215 with tumors between 3.1 and 4.0 cm in diameter. Median clinical diameter of renal cell carcinoma in the whole series was 2.93 cm (range 0.8 to 4.0). Tumor stage was pT1a, pT1b and pT3 in 84.5%, 8.0% and 7.5% of cases, respectively. Tumor grade was 1 to 3 in 24.5%, 65.0% and 10.6% of cases, respectively. The renal cell carcinoma histological subtype was clear cell carcinoma in 77.9% of patients, papillary carcinoma in 15.3% and chromophobe carcinoma in 6.8%. Advanced tumor stage (pT3) was found in 3.0%, 5.1% and 12.1% of the patients in the 2, 3 and 4 cm groups, respectively (p <0.05). Grade 3 was found in 7.1%, 9.0% and 14.0% of the patients in the 2, 3 and 4 cm groups, respectively (p <0.05). Metastases at diagnosis were found in 3.0%, 2.6% and 6.0% of the patients in the 2, 3 and 4 cm groups, respectively. Negative prognostic features increase with tumor diameter and they are associated with even small tumors. However, above a tumor size of 3.0 cm there is a sharp increase in the incidence of negative prognostic parameters. New diagnostic tests are warranted to better stratify patients with respect to treatment aggressiveness for small incidental renal tumors.

Renal cell carcinoma sub‐typing by histopathology and fluorescence in situ hybridization on a needle‐biopsy specimen

To determine the subtype of renal cell carcinoma (RCC) on needle-core biopsies of renal masses using histopathology and fluorescence in situ hybridization (FISH), and to evaluate the use of interphase FISH to augment the accuracy of needle-core biopsies. Histology correlates with prognosis in RCC but, historically, biopsies are inaccurate for histological subtype. As histological subtypes of RCC have distinct cytogenetic abnormalities (loss of 3p in clear cell, trisomy 7 or 17 in papillary and widespread chromosomal losses in chromophobe), we hypothesized that FISH would improve the accuracy of biopsies. Forty patients with renal masses underwent nephrectomy, yielding 42 tumours. Needle-core biopsies were taken of the mass immediately after surgery. Interphase FISH was performed on one core for chromosomes 3, 7, 10, 13, 17, and 21 and the locus 3p25-26. Histopathology was performed on a second core. Results were compared in a 'blinded' fashion with final pathology. In all, 36 of 42 masses were RCC or oncocytoma. Histopathology of the biopsy correctly identified the tumour subtype in 27 (75%), while four (11%) were incorrectly classified and five (14%) were inadequate for diagnosis. With the addition of FISH, 31 (86%) were correctly subtyped, while two (6%) were incorrect and three (8%) were inadequate. In cases with adequate tissue, histology alone was 87% accurate, while the combined method was 94% accurate. Needle-core biopsy of renal tumours provides adequate material for evaluation of histological subtype. Adding FISH to histopathology might improve the accuracy of kidney tumour biopsies, providing important prognostic information that can guide management decisions.

Common and Uncommon Histologic Subtypes of Renal Cell Carcinoma: Imaging Spectrum with Pathologic Correlation

Renal cell carcinoma (RCC) is a cause of significant morbidity and mortality, with an estimated 35,000 new cases and 12,480 deaths in the United States in 2003. Recent advances in imaging technology, pathology, urology, and oncology permit early diagnosis of RCC and facilitate optimal management. The 2004 World Health Organization classification for renal neoplasms recognizes several distinct histologic subtypes of RCC. These subtypes include clear cell RCC, papillary RCC, chromophobe RCC, hereditary cancer syndromes, multilocular cystic RCC, collecting duct carcinoma, medullary carcinoma, mucinous tubular and spindle cell carcinoma, neuroblastoma-associated RCC, Xp11.2 translocation-TFE3 carcinoma, and unclassified lesions. Different histologic subtypes of RCC have characteristic histomorphologic and biologic profiles. Clear cell RCC is the most common subtype and has a less favorable prognosis (stage for stage) than do papillary RCC and chromophobe RCC. Collecting duct carcinoma and renal medullary carcinoma are associated with aggressive clinical behavior and a poor prognosis.

Gender discrepancies in the diagnosis of renal cortical tumors

Renal cell carcinoma (RCC) is more common in men than women although the relationship between sex and histologic sub-type of RCC is unknown. The Columbia University Urologic Oncology Database of 1,105 patients who underwent nephrectomy from 1990-2005 was reviewed. 1,018 patients were included who underwent renal surgery with complete demographic data and post-operative pathologic information; 49 with incomplete information and 36 with "granular" histology were excluded. Differences in histology, size and volume of primary tumor, laterality, chief complaint, age, pathologic stage and status were evaluated by sex using ANOVA techniques. The cohort included 671 (66.1%) men and 344 (33.8%) women. There were no differences in age (61.0 vs. 60.7 years, P = 0.36), size (6.22 vs. 5.53 cm, P = 0.08) or volume (305 vs. 129cc, P = 0.07) of primary tumor. Men were more likely to have bilateral tumors (9.6 vs. 3.5%, P = 0.003). A greater percentage of men had malignant pathologic histology at nephrectomy (90.9 vs. 84.0%, P = 0.002). The rate of malignancy for women increased from 44.5% for tumors < 1 cm to 92.7% for tumors greater than 10 cm; there was no trend noted in men. Women had a greater percentage of conventional RCC (77.2 vs. 70.5%, P = 0.04). When analyzed by histologic sub-type, men were more likely to have papillary histology than women (17.4 vs. 4.5%), women were more likely to have chromophobe histology (11.2 vs. 5.0%; P = 0.006). Differences in demographics, pathologic parameters and histologic sub-typing are observed between men and women treated for renal masses.

Second Primary Malignancies Associated With Renal Cell Carcinoma Histological Subtypes

Renal cell carcinoma has been linked to numerous secondary malignancies. We evaluated the risk of secondary malignancies by renal cell carcinoma histological subtype in patients with clear cell, papillary and chromophobe renal cell carcinoma. We studied 2,722 patients who underwent nephrectomy for sporadic renal cell carcinoma at our institution between 1970 and 2000. All specimens were reviewed by a single urological pathologist for histological subtype. Associations of second primary malignancies by histological subtype were evaluated using the chi-square and Fisher exact tests. Of the patients studied 2,188 (80.4%) had clear cell, 378 (13.9%) had papillary and 128 (4.7%) had chromophobe renal cell carcinoma. Patients with papillary renal cell carcinoma were significantly more likely to have colon cancer (p = 0.041), prostate cancer (p = 0.003), any second malignancy (p <0.001) and multiple malignancies (p <0.001) compared with patients with clear cell renal cell carcinoma. In addition, patients with chromophobe renal cell carcinoma were significantly more likely to have colon cancer than patients with clear cell renal cell carcinoma (p = 0.020). Although patients with papillary renal cell carcinoma were more likely to have bladder cancer, the incidence did not differ significantly compared with that in patients harboring clear cell and chromophobe renal cell carcinoma (p = 0.193). We did not find a significant difference in the incidence of breast cancer, lung cancer, rectal cancer or lymphoma among histological subtypes. Our data indicate that patients with papillary renal cell carcinoma are more likely to harbor secondary malignancies, including colon and prostate cancer, than patients with clear cell renal cell carcinoma. These results may have important implications for patient education and followup evaluation, and they should prompt mechanistic investigations.

Expression of Hypoxia Inducible Factor-1α and 2α in Genetically Distinct Early Renal Cortical Tumors

The role of the HIF class of transcription factors has been implicated to be a critical step in clear cell kidney tumorigenesis. To assess if HIF over expression is a prominent feature of other renal cell carcinoma histological subtypes we characterized the expression of HIF-1alpha and HIF-2alpha in genetically distinct early renal cortical tumors. Nascent renal tumors of distinct histology from patients with a hereditary renal tumor syndrome were characterized for HIF expression using high amplification immunohistochemistry. In addition, indirect immunofluorescence and confocal microscopy were used for subcellular localization of HIF-1alpha and 2alpha in clear cell renal carcinoma cells. Clear cell RCC tumors from patients with von Hippel-Lindau disease strongly expressed HIF-1alpha and HIF-2alpha (10 of 12 and 12 of 12 tumors, respectively). Chromophobe tumors from patients with Birt-Hogg-Dubé syndrome expressed predominantly HIF-2alpha with weaker HIF-1alpha expression (12 of 12 and 6 of 12 tumors, respectively). Consistent HIF-1alpha expression was not seen in type I papillary tumors from patients with hereditary papillary renal carcinoma (3 of 12 tumors). However, half of the type I papillary tumors (6 of 12) expressed HIF-2alpha. Differential patterns of HIF-1alpha and HIF-2alpha protein over expression were found among the 3 human kidney tumor types associated with multifocal hereditary kidney tumor syndromes. Consistent, simultaneous over expression of HIF-1alpha and HIF-2alpha appears to be specific to VHL negative clear cell renal cell carcinoma. Consistent HIF-2alpha expression was found in all 3 renal cortical tumor subtypes, suggesting a pivotal role in renal cortical tumorigenesis. Differential function of HIF-1alpha vs HIF-2alpha is suggested by the distinct subcellular localization pattern of HIF-1alpha and HIF-2alpha in clear cell renal carcinoma cells.

Prognostic Value of Histologic Subtypes in Renal Cell Carcinoma: A Multicenter Experience

To analyze to what extent histologic subtype is of prognostic importance in renal cell carcinoma based on a large, international, multicenter experience. Four thousand sixty-three patients from eight international centers were included in this retrospective study. Histologic subtype (1997 International Union Against Cancer [UICC] criteria of tumor response), age, sex, TNM stage, Fuhrman grade, tumor size, Eastern Cooperative Oncology Goup performance status (ECOG PS), and overall survival were determined in all cases. The prognostic values of clear cell, papillary, and chromophobe histologic features were assessed by uni- and multivariate analysis using the Kaplan-Meier method and Cox model, respectively. Clear cell, papillary, and chromophobe carcinomas accounted for 3,564 (87.7%), 396 (9.7%) and 103 (2.5%) cases, respectively. In univariate analysis, a trend toward a better survival was observed when clear cell, papillary, and chromophobe histologies were considered prognostic categories (log-rank P = .0007). However, in multivariate analysis, TNM stage, Fuhrman grade and ECOG PS, but not histology, were retained as independent prognostic variables (P < .001). The stratification in three main renal cell carcinoma histologic subtypes as defined by the 1997 UICC-American Joint Committee on Cancer consensus should not be considered a major prognostic variable comparable to TNM stage, Fuhrman grade and ECOG PS.

Altered messenger RNA and protein expressions for insulin‐like growth factor family members in clear cell and papillary renal cell carcinomas

The purpose of the present paper was to describe the pattern of expression of insulin-like growth factor (IGF-I) and its regulatory binding proteins (IGFBP) in renal cell carcinoma (RCC). The expressions of mRNA and protein for various IGF members were assessed in 24 paired normal and malignant human renal tissues (16 clear cell and 8 papillary RCC) using semiquantitative reverse transcription-polymerase chain reaction and immunohistochemistry. Paired tissue samples were also obtained from six patients with oncocytoma in order to compare the specificity of changes in IGF/IGFBP expression between tumors derived from proximal (RCC) and distal (oncocytoma) tubular epithelium. Clear cell RCC were characterized by significant increases in the mRNA expression of IGF-I, IGFBP-3 and IGFBP-6 while papillary RCC exhibited down-regulated expression of IGF-I, IGFBP-4 and IGFBP-5. The IGFBP-2, IGFBP-4 and IGFBP-5 mRNA were down-regulated in oncocytomas. Semiquantitative assessment of immunohistochemical staining demonstrated significant increases in epithelial associated IGF-I and IGFBP-3 in clear cell RCC, increased IGFBP-5 protein in papillary RCC and no significant changes in IGF/IGFBP protein expression in oncocytoma. The expression of IGF-I and certain IGFBP is significantly altered in RCC compared with normal renal tissue and oncocytomas. This altered expression is differentially regulated according to the histologic subtype of RCC, and suggests that the IGF/IGFBP axis may play an important role in determining the malignant phenotype of RCC.

Renal Cell Carcinoma in the Solitary Kidney: An Analysis of Complications and Outcome After Nephron Sparing Surgery

We evaluated surgical techniques, pathological features and extended outcomes in patients with renal cell carcinoma in a solitary kidney treated with surgical excision. Between 1970 and 1998, 76 patients underwent nephron sparing surgery for sporadic renal cell carcinoma in a solitary kidney, including 63 with tissue specimens available for pathological review who comprised the cohort. Six (9.5%) patients had a congenitally absent kidney and 57 (90.5%) had previously undergone contralateral nephrectomy for renal cell carcinoma. The clinical and pathological features examined were patient age at nephron sparing surgery, sex, type of nephron sparing surgery (enucleation, partial nephrectomy or ex vivo resection), tumor size, nuclear grade, histological subtype and 1997 tumor stage. Overall cancer specific, local recurrence-free and metastasis-free survival as well as early (within 30 days of nephron sparing surgery) and late (30 days to 1 year after nephron sparing surgery) complications were assessed. Univariate and multivariate analyses were done to test for the associations of clinical and pathological features with outcome. Most patients were treated with enucleation (36.5%), standard partial nephrectomy (38.1%) or the 2 procedures (11.1%) and in 8 (12.7%) ex vivo tumor resection was done. The renal cell carcinoma histological subtypes were clear cell in 82.5% of cases, papillary in 15.9% and chromophobe in 1.6%. Grade was 1 to 3 in 10 (15.9%), 42 (66.7%) and 10 (15.9%) tumors, respectively. At 5 and 10 years the overall survival rate was 74.7% and 45.8%, the cancer specific survival rate was 80.7% and 63.7%, the local recurrence-free survival rate was 89.2% and 80.3%, and the metastasis-free survival rate was 69% and 50.4%, respectively. Tumor stage and nuclear grade were significantly associated with death from any cause, death from renal cell carcinoma and distant metastases on multivariate analysis. Notably no patient with papillary or chromophobe renal cell carcinoma died of renal cell carcinoma, or had recurrence or metastasis. The type of nephron sparing surgery was not significantly associated with outcome, although there were too few patients with recurrence to assess the association of the type of nephron sparing surgery with local recurrence. The most common early complication was acute renal failure in 12.7% of cases, while the most common late complications were proteinuria in 15.9% and renal insufficiency in 12.7%. The 1997 tumor stage and nuclear grade were significant predictors of death from any cause, death from renal cell carcinoma and distant metastases in patients treated with nephron sparing surgery for renal cell carcinoma involving a solitary kidney. Nephron sparing surgery in a solitary kidney can be performed safely and with minimal morbidity.