Behavior Of Renal Cell Carcinoma Research Articles

Pathways of Dysregulation in Renal Cell Carcinoma: Rational Approaches to Development of Novel Treatment

Recent developments have involved a series of novel agents that produce clinical benefit in patients with advanced clear-cell renal cell carcinoma (RCC). The molecular characteristics of RCC, pathways involved in growth and progression, and development of targeted therapeutic approaches have become the focus of many investigators in the past decade. A variety of genetic abnormalities, molecular markers and drugs that target these markers or alter the genetic expression of certain regulatory proteins, have been identified and might have clinical significance for prognosis and treatment. However, specific markers associated with RCC and further development of novel single or combination targeted therapies is now required. An understanding of the complicated and unique biologic behavior of RCC and its various histologic subtypes is crucial for the continued development of novel and targeted therapies.

Isolated liver metastasis from a renal cell carcinoma 12 years after nephrectomy: report of a case and literature review.

We present a rare case of isolated liver metastasis from renal cell carcinoma 12 years after complete resection of the primary site. Such abnormal behavior of renal cell carcinoma has been reported elsewhere in the literature; thus, careful long-term surveillance should be performed in patients with a past history of renal cell carcinoma, even after radical resection of the primary site. We present also contrast-enhanced sonographic findings for this case.

Association of Mast Cells with Microvessel Density in Renal Cell Carcinomas

BackgroundGrowth of solid tumors requires angiogenesis. Evidence indicates that mast cells (MCs) play an important role in tumor angiogenesis. The aim of this study was to investigate the possible effects of angiogenesis and the presence of MCs on the prognosis of renal cell carcinoma (RCC). MethodsSeventy-one patients who underwent radical nephrectomy for RCC were included in this study. Paraffin sections from tumor and nonneoplastic kidney were stained with CD31 antibody with the standard streptavidin-biotin immunperoxidase method. Microvessels were quantified by a stereologic method. Tumors and the surrounding area were also stained with toludine blue stain to show MCs in tumor and surrounding tissue. The correlation between microvessels and MC counts was evaluated and compared with tumor stage, grade, and other clinicopathologic parameters. ResultsMCs in RCC and peritumoral areas were observed to be greater than nonneoplastic kidney tissue. No correlation was found between MC number and various clinicopathologic features such as tumor size, stage, grade, and patient survival. No association was noted between angiogenesis and clinicopathologic features. On the other hand, significant correlation was found between the number of MCs and microvessel density (p=0.034, r=0.295). ConclusionOur results suggest that MC infiltration may contribute to tumor angiogenesis and acceleration of tumor growth, whereas stereologic assessment of angiogenesis does not help to predict biologic behavior in RCC. Further research is required to confirm these observations.

Analysis of Matrix Metalloproteinase-9 Expression in Renal Cell Carcinoma

Background: Matrix metalloproteinases (MMPs) are involved in the degradation of the extracellular matrix, which is an important step in tumor invasion and metastasis. A positive correlation between the expression of MMP-9 and aggressive behavior of renal cell carcinomas (RCCs) has been reported. MMP-9 expression in RCCs and adjacent normal kidney tissues were examined in this study. Materials and Methods: Twenty-five patients pathologically diagnosed as clear cell RCCs, from specimens obtained at radical nephrectomy, between May 2003 and December 2004 were enrolled in this study. MMP-9 activity was estimated using gelatin zymography, and quantified using a laser densitometer. The results were compared with clinicopathological characteristics. Results: The expression of MMP-9 was significantly elevated in the RCC compared with non-tumor kidney specimens (p4 cm) or vascular invasion were significantly higher than in those without these clinical manifestations (p

Incidencia creciente en el carcinoma de células renales

ObjectivesTo analyze the change in the behavior of renal cell carcinoma for its presentation, treatment, histology and mortality during a 17 year period. Material and methodRetrospective study on 212 patients diagnosed with renal cell carcinoma in our Department from the year 1988 up to 2004, analyzing the clinical and demographic data and comparing them to each other according to two periods: 1988-1996 and 1997-2004. ResultsAn increase has been appreciated in the incidence of renal tumors in the second period and in a same way an increase in the incidental diagnosis and in the practice of nephron sparing surgery. Clear cell type was the most frequent in both periods and tumoral size was higher in the first period than in second. TNM stage I was the most frequent, although in first period it was higher percentage of stage IV. Cause-specific mortality has increased in the last years. ConclusionAn increase is appreciated in the incidence of renal cell tumors. Although the diagnosis is in earlier stages, a descent in the mortality has not been found.

Prognostic value of the expression of Ki-67, CD44 and vascular endothelial growth factor, and microvessel invasion, in renal cell carcinoma.

To determine if use of cell proliferation, cell adhesion, level of angiogenesis-related factors and presence of microscopic vascular invasion (MVI) could better predict the biological behaviour of renal cell carcinoma (RCC), which has a widely variable clinical outcome despite the use of conventional prognostic factors (staging and grading). The expression of Ki-67, CD44H and vascular endothelial growth factor (VEGF) were assessed immunohistochemically in formalin-fixed, paraffin-embedded tissues from 48 RCCs, using a Ki-67 labelling index (LI), CD44 LI and level of VEGF expression, respectively. In addition all the pathological slides were reviewed retrospectively for the presence and absence of MVI. The prognostic value of all the variables assessed was then evaluated, and correlated with the usual prognostic variables and cancer-specific survival. Univariate analysis of cancer-specific survival showed that tumour stage (P < 0.001), tumour size (P = 0.005), metastasis, MVI, Ki-67 LI, CD44H LI and VEGF expression (all P < 0.001) were predictors of tumour-related death. There was a statistical correlation between CD44H LI and each of Ki-67 LI (r = 0.61), expression level of VEGF (r = 0.72) and presence of MVI (r = 0.71). Independent predictors of cancer-specific survival in a multivariate analysis were: in all patients with RCC, the MVI (P = 0.003) and VEGF expression (P = 0.01); in those with no metastases, MVI (P = 0.01); in patients with no MVI, VEGF (P = 0.04); and in patients with MVI, Ki-67 LI (P = 0.003). No independent predictor was identified in patient with metastases. This study suggests that cell proliferation, cell adhesion, the level of VEGF expression and the presence of MVI represent a complex tumour-host interaction that may favour the progression of RCC. Cell proliferation, CD44H and VEGF expression appear to be powerful markers for identifying patients with an adverse prognosis.

Basic biology and clinical behavior of renal cell carcinoma.

Renal cell carcinoma (RCC) accounted for over 31,000 new cases of cancer and led to approximately 12,000 deaths in the United States in 2001.1Nearly one-third of RCC cases present with metastatic disease and approximately 30% of those treated for localized disease eventually relapse.2Renal cell carcinoma occurs twice as often in men and most commonly occurs during the fifth through seventh decades of life, but has been reported in younger patients.2

Renal cell carcinoma in acquired cystic kidney disease: Volume growth rate determined by helical computed tomography

The aim of this study is to determine the growth rate and behavior of renal cell carcinoma in chronic hemodialysis patients with acquired cystic kidney disease (ACKD). Renal cell carcinomas in 17 hemodialysis patients (mean age, 52 ± 11 years; mean hemodialysis duration, 7.2 ± 3.3 years) with ACKD were examined with helical computed tomography (CT) for 0.5 to 6.0 years (mean, 2.1 ± 1.9 years). The 17 renal cell carcinomas were histologically proven and graded after nephrectomy (16 patients) or autopsy (1 patient). Tumor volume was estimated by counting the number of pixels in the tumor and a 1-cm2 area on helical computed tomographic scan using a personal computer. Estimated volume growth rates and doubling times of the carcinoma were correlated with histological grades. Fifteen of the 17 neoplasms (88%) were less than 3 cm in diameter at initial CT. The overall volume growth rate was 0.07 to 17.34 cm3/y (mean, 4.14 ± 5.66 cm3/y), and the estimated volume-doubling time was 0.08 to 23.31 years (mean, 5.09 ± 6.99 years). The mean growth rate of the 3 grade 3 carcinomas was 6.01 ± 4.50 cm3/y (range, 0.88 to 9.28 cm3/y), which was significantly greater than that of the 9 grade 1 carcinomas (0.40 ± 0.40 cm3/y; range, 0.09 to 1.37 cm3/y) or the 5 grade 2 tumors (0.79 ± 0.74 cm3/y; range, 0.12 to 2.00 cm3/y). Eleven of the 17 carcinomas (65%) had more than a 1-year volume-doubling time. The 3 grade 3 neoplasms and 1 of the grade 2 lesions had less than a 0.5-year doubling time.

Absence of correlation of MUC1 expression to malignant behavior of renal cell carcinoma in experimental systems.

A correlation between MUC1 expression in renal cell carcinomas (RCCs) and the clinical stages was previously demonstrated. To assess whether MUC1 expression is causally related to malignant tumor behavior, MUC1 cDNA was stably transfected into a renal carcinoma cell line SN12C that expresses trace levels of MUC1. MUC1 with sialylated carbohydrate chains was detected on the surface of transfected cells in two independent experiments. There was no correlation between MUC1 expression and in vitro growth and motility. In vivo growth of the transfectants at the site of orthotopic transplantation in nude mice was slower than mock transfected cells. Therefore, MUC1 alone did not seem to confer a malignant phenotype to RCCs.

Assessment of proliferating cell nuclear antigen expression and prognosis in patients with renal cell carcinoma with pulmonary metastases.

The presence of proliferating cell nuclear antigen (PCNA) has been suggested as a more important prognostic marker than either grade or mitotic index in the prognosis of patients with renal cell carcinoma. We assessed the immunoreactivity of PCNA in primary lesions and pulmonary metastases from patients with renal cell carcinoma and correlated the results with various histopathologic features and prognostic factors. We studied the relationship between PCNA expression and clinical prognostic factors from resected primary lesions and pulmonary metastases from 10 patients and primary lesions from 32 patients with renal cell carcinoma without metastases. The cells were immunohistochemically stained with PCNA monoclonal antibody (PC-10) and 1000 nuclei were counted. The results were expressed as a ratio of stained to total cells (PCNA labeling index, LI %). The PCNA LI of pulmonary metastatic nuclei was significantly higher than the PCNA LI of renal lesions either from patients with (P < 0.05) or without (P < 0.01) metastases. Also, the mean PCNA LI of the pulmonary lesions in patients dying within 3 years of diagnosis was higher than the mean PCNA LI of patients surviving greater than 3 years. Our findings suggest that the PCNA LI, which was determined by immunohistochemical analysis, is an important marker reflecting the biologic behavior of renal cell carcinomas. The degree of PCNA expression in this study was of prognostic significance.

Renal cell carcinoma in autosomal dominant polycystic kidney disease.

To provide information on the clinical presentation, diagnosis, pathology, and biologic behavior of renal cell carcinoma in patients with autosomal dominant polycystic kidney disease (ADPKD), three cases seen at this institution between 1955 and 1992, as well as the cases reported in the literature, were reviewed in detail. No male predominance was observed (12 men, 13 women) in the 25 patients who met the inclusion criteria. The age of presentation was earlier than that seen in the general population (45 versus 61 yr). Fever, night sweats, and weight loss were prominent at presentation. Fever is a more common presenting symptom of renal cell carcinoma in ADPKD (32%) than in the general population (7%). Twenty percent of the patients had metastatic disease at presentation. Even with computed tomography and magnetic resonance, the diagnosis was difficult and often delayed, and the accumulation of 111In-labeled white blood cells can wrongly suggest a cyst infection. Renal cell carcinoma in ADPKD is more often concurrently bilateral (12 versus 1 to 5%), multicentric (28 versus 6%), and sarcomatoid in type (33 versus 1 to 5%) than in the general population. Because previous studies have failed to demonstrate a higher prevalence of renal cell carcinoma in ADPKD, this information suggests either a malignant potential restricted to a small subset of patients with this disease or an alteration in the biologic behavior of renal cell carcinoma when it develops in the setting of ADPKD.

Ten years survival after recurrent intracranial metastases from a renal cell carcinoma

The clinical behaviour of renal cell carcinoma is often unpredictable. We report a patient who underwent three palliative resections over 10 years for recurrent intracerebral metastases from a renal cell carcinoma.

Renal cell carcinoma.

The behavior of renal cell carcinoma remains one of the most unpredictable of the genitourinary neoplasms. Once this disease has spread beyond the confines of the kidney, it is extremely difficult to control. This year, emphasis has focused on the characteristic cytogenetic and chromosomal changes that are seen in this tumor that help to explain partially its enigmatic behavior. Immunotherapy remains the mainstay of nonsurgical therapy. Recent studies have examined the efficacy of using combinations of interferons, interleukin-2, or specific subpopulations of lymphoid cells to control metastatic renal cell carcinoma. The role of surgery in metastatic disease, tumor extending into the vena cava, and parenchyma-sparing operations continues to be examined. This review examines the most recent literature on each of these aspects in the treatment of this difficult and challenging tumor.

Streptozotocin によるマウス腎化学発癌過程の病理組織学的検討

Renal adenocarcinoma was induced in CBA/H/T6J mice by a single intraperitoneal injection of 250 mg/kg of streptozotocin (STZ). Light and electron microscopic examination revealed that the carcinoma was a granular cell type-adenocarcinoma with abundant microvilli, basal lamina and intermediate junction indicating an epithelial cell origin. In histopathological analysis of the process of this carcinogenesis, all of the kidneys examined had a dilatation of proximal tubules in the second month and thereafter. In the fifth month, one of eight kidneys developed an adenoma. The adenoma was found in all the kidneys after the ninth month. An adenocarcinoma developed in one of the 14 kidneys in the twelfth month and in all others in the fifteenth month. In vivo labeling of bromodeoxyuridine on the cells in various stages demonstrated an increase of the labeling index which paralleled with progression of the carcinogenesis process. This finding in in vivo analysis of cell proliferation also supports the idea that serial changes of the kidney which are histopathologically proven correspond to the carcinogenesis process. The original carcinoma (STZ-RCC) has serially been passed in vivo at the present. Intrasplenic injection of STZ-RCC yielded multiple macroscopic foci of metastasis in the liver. This indicates that STZ-RCC has a malignant potential. Thus, STZ-induced mouse renal adenocarcinoma can be applied to the model system to investigate carcinogenesis and biological behaviors of renal cell carcinoma.

Metastatic patterns of renal carcinoma: an analysis of 687 necropsies.

The metastatic behaviour of renal cell carcinoma has been studied in a series of 687 necropsies. The observations were consistent with the concept of "metastatic inefficiency", in that in 295 cases, including 25 with renal vein invasion, there were no detectable metastases. In the present series, renal vein involvement was not an important prognostic factor in stage 1 or 2 disease. In 73% of cases without lung metastases there were none in other sites, and in 84% of those with lung metastases there were others elsewhere, consistent with a metastatic "cascade" in which metastases first developed in the lungs and were later detected in other organs. However, the observations did not permit discrimination between anatomic cascades, in which other organs were seeded from metastasizing pulmonary metastases, and temporal cascades, in which the other were seeded at the same time as the lungs, but with fewer cancer cells. The patterns of arterial metastasis were consistent with the "seed-and-soil" hypothesis, and a novel index was developed to quantify differential organ "soils". The contralateral kidney was not the best soil for metastases from renal carcinoma. Given the presence of lymph node metastasis, the probability of heamatogenous metastasis is 90%. However, in the absence of nodal metastasis, approximately half the cases had haematogenous metastasis.

Solitary Late Recurrence of Renal Cell Carcinoma

Solitary late recurrence is an unpredictable behavior pattern of renal cell carcinoma. We describe a patient with recurrence at the cranial bone 10 years after surgical management and another with recurrence at the sacral bone 13 years after treatment with radiotherapy and alpha-interferon. Both patients have been followed satisfactorily for 9 months. Unpredictable behavior of renal cell carcinoma makes lifelong followup of patients necessary. If a solitary recurrence is detected operative management definitely should be considered depending on the site of recurrence.

Prognostic significance of nuclear sizing in renal cell carcinoma

Nuclear grading has been reported to be a useful prognostic indicator in renal cell carcinoma (RCC). One of the components of nuclear grading, the size or cross-sectional area of cancerous nuclei, might by itself be a determinant of biologic behavior in RCC. To examine this possibility, a retrospective qualitative analysis of clinical and histopathologic parameters in 32 patients with Robson Stage 3 RCC was conducted. Patients with disproportionately larger nuclei in their RCC cells had a statistically shorter median survival (p < 0.009). The examination of the relative areas of cancerous nuclei, herein termed nuclear sizing, appears to be a prognostic discriminant in primary RCC.

Organ-preserving surgery in renal cell carcinoma: tumor enucleation versus partial kidney resection.

Organ-preserving surgery is attempted in cases of small renal cell carcinoma, especially when such tumors occur bilaterally or in an anatomical or functional solitary kidney. It is still a matter of debate how much of the peritumoral renal tissue has to be removed for optimal cure rates. Enucleation of the neoplasm as well as partial nephrectomy have been advocated. The relation of renal cell carcinomas to their pseudocapsule and to the adjacent renal parenchyma was examined using microangiographic and histopathologic techniques. In a number of cases in our series a total or partial enucleation ex situ permitted an investigation of the enucleate and tumor bed. The pseudocapsule of all tumors was invaded by neoplastic cells and the surrounding renal parenchyma was often infiltrated by the carcinoma, even around some of the smallest tumors. Comparison of tumor vascularization with the histologic features led to the suggestion of a more aggressive behavior of renal cell carcinomas once they have exceeded a certain size. Thus, in contrast to larger carcinomas, tumors with a diameter of less than 6 cm most often show a radial vascular pattern and lack central necrosis. These parameters can be evaluated by noninvasive investigative techniques. Smaller tumors appear amenable to conservative surgical treatment; however, in view of our histopathologic findings, a sufficiently wide margin of adjacent renal parenchyma should always be removed with the tumor.