Biomedical subjects

Eugene D Kwon

Publications and source records attributed to Eugene D Kwon.

At least 19 recordsLinked to original sources

PubMed2007

Early effects of pharmacological androgen deprivation in human prostate cancer.

OBJECTIVES: To assess the early histological effects of pharmacological androgen deprivation (AD), which have been assessed only over longer periods, as surgical castration leads rapidly to diminished cell proliferation and enhanced cell death within the prostate. PATIENTS AND METHODS: With Institutional Review Board approval, 35 patients were randomly assigned (seven in each group) to receive 0, 7, 14, 21 and 28 days of AD (flutamide, 250 mg orally three times/day, and one injection with leuprolide acetate 7.5 mg) before radical prostatectomy. The surgical specimens were assessed by conventional histology and immunohistochemistry, while macroarray analysis and quantitative real-time polymerase chain reaction (QRT-PCR) were used to examine gene expression. RESULTS: There were morphological changes within the prostatic tissues as early as 7 days after initiating AD, similar to the response to castration. There was tumour cell vacuolization indicating cellular injury, glandular atrophy and mononuclear cell infiltration as prominent and progressive effects but, by contrast with castration studies, there were no changes in epithelial proliferation or apoptosis. Macroarray analysis, validated by QRT-PCR and immunohistochemistry, showed up-regulation of numerous and potentially counter-effective genes involved in the cell cycle and apoptosis. CONCLUSIONS: Pharmacological AD induces significant involution within prostatic tissues over 7-28 days, but allows the persistence of some viable tumour cells capable of proliferation.

Adenocarcinoma↗

PubMed2006

Outcomes of Gleason score 10 prostate carcinoma treated by radical prostatectomy.

OBJECTIVES: To evaluate the outcome of radical prostatectomy for the rarest and most poorly differentiated prostate tumors of all: those with Gleason score 10. Controversy exists as to which form of therapy is most effective for high-grade prostate cancer (PCa). METHODS: We retrospectively reviewed the charts of all patients with pathologic Gleason score 10 PCa treated at our institution with radical prostatectomy from 1977 to 1999. All pathology specimens were reviewed by a urologic pathologist, and 13 cases with true Gleason score 10 PCa were identified. The preoperative covariables (prostate-specific antigen level, biopsy Gleason score, and clinical stage), perioperative covariables (pathologic stage, margin status, and tumor ploidy), and postoperative covariables (prostate-specific antigen level and adjuvant and salvage treatments) were assessed with respect to the oncologic outcomes. RESULTS: The median follow-up was 4.2 years. Preoperatively, only 4 of the 13 cases were correctly identified at biopsy, and the median preoperative prostate-specific antigen level was 4.5 ng/mL (interquartile range 0.3 to 12.5). Pathologic examination showed a small cell component in 7 cases, seminal vesicle invasion in 11, and positive lymph nodes in 3. Six patients developed recurrent PCa: three local, two systemic, and one biochemical recurrence. The biochemical recurrence-free and cancer-specific survival rate at 5 years was 53.8% and 76.9%, respectively. CONCLUSIONS: Gleason score 10 PCa is a highly aggressive disease that is usually lethal if managed conservatively. The results of the present study have provided some evidence that radical prostatectomy may be of benefit to patients with Gleason score 10 PCa.

Aged↗

PubMed2006

Urachal carcinoma: clinicopathologic features and long-term outcomes of an aggressive malignancy.

BACKGROUND: Urachal carcinoma (UrC) is a rare malignancy, and patients with this disease have a poor prognosis. In this article, the authors report 50 years of experience with this tumor at the Mayo Clinic. METHODS: A urachal mass was described in 130 patients, and 66 of those masses were malignant. The authors identified multivariate predictors of malignancy in clinically diagnosed urachal masses and predictors of UrC-specific survival. This report presents a novel 4-category staging system for UrC along with the treatment history of this tumor and the results of salvage therapy. RESULTS: Twenty women and 46 men were identified with UrC. The strongest predictors of malignancy in a urachal mass were hematuria and age older than 55 years. The 5-year cancer-specific survival rate was 49%. The new Mayo staging system was less complicated than the Sheldon system, although both systems predicted cancer-specific mortality equally well. Positive surgical margins (hazard ratio [HR], 4.7), high tumor grade (HR, 3.6), positive local lymph nodes (HR, 5.1), metastases at diagnosis (HR, 3.3), advanced tumor stage (HR, 4.8), failure to perform umbilectomy (HR, 3.0), and primary radiation therapy (HR, 2.9) were all univariately associated with death (P <.05). Only grade and margins were significant in the multivariate analysis. No survival benefit was noted for lymphadenectomy or adjuvant therapy. Salvage surgery resulted in a long-term cure for 50% of patients who had local recurrences. No effective treatment was identified for patients with metastatic UrC. CONCLUSIONS: Early and complete extended partial cystectomy, including umbilectomy, is critical to the survival of patients with UrC. The authors recommend using the Mayo staging system in future studies because of its simplicity. The current results indicated that the most important predictors of prognosis were tumor grade and surgical margin status.

Cohort Studies↗

PubMed2006

Mononuclear cell infiltration in clear-cell renal cell carcinoma independently predicts patient survival.

BACKGROUND: The impact of mononuclear cell infiltration on renal cell carcinoma (RCC) biology has been controversial, previously reported to be associated with either a favorable or unfavorable prognosis. The objective of the current study was to evaluate associations between mononuclear cell infiltration in routinely prepared paraffin-embedded specimens with survival in patients with clear-cell RCC. METHODS: A total of 306 patients were identified treated with nephrectomy for clear-cell RCC between 1990 and 1994. A single urologic pathologist, blinded to patient outcome, reviewed the specimens and quantified the extent of mononuclear cell infiltration as absent, focal, moderate, or marked. Cancer-specific survival was estimated using the Kaplan-Meier method. Associations of mononuclear cell infiltration with death from RCC were assessed using Cox proportional hazards regression models. RESULTS: At last follow-up, 173 of the 306 patients studied had died, including 96 patients who died from RCC. Mononuclear cell infiltration was absent in 165 (54%), focal in 70 (23%), moderate in 53 (17%), and marked in 18 (6%). Univariately, patients with specimens that had mononuclear cell infiltration were over 2 times more likely to die from RCC compared with patients whose specimens exhibited no mononuclear cell infiltration (risk ratio, 2.63; P < .001). After adjusting for the Mayo Clinic SSIGN (stage, size, grade, and necrosis) score, patients with specimens that had mononuclear cell infiltration exhibited a significantly increased likelihood of dying from RCC compared with patients whose specimens had no mononuclear cell infiltration (risk ratio, 1.61; P = .028). CONCLUSIONS: Mononuclear cell infiltration is associated with death from RCC even after multivariate adjustment. Routine documentation of mononuclear cell infiltration is recommended during the pathologic assessment of RCC.

Carcinoma, Renal Cell↗

PubMed2006

High expression levels of survivin protein independently predict a poor outcome for patients who undergo surgery for clear cell renal cell carcinoma.

BACKGROUND: In a previous study of gene array data, the authors identified survivin as a candidate marker of aggressiveness in clear cell renal cell carcinoma (ccRCC). What remained in question was whether survivin expression at the protein level is an independent predictor of disease progression and cancer-specific survival. METHODS: Between 1990 and 1994, 312 patients underwent nephrectomy for ccRCC at Mayo Clinic Rochester and had paraffin tissue available. The authors performed immunohistochemistry with antisurvivin antibody, quantitated the expression by using an image-analysis system, and analyzed the association of survivin expression with disease progression and cancer-specific survival. RESULTS: Within the cohort, 97 patients (31.1%) had high levels of survivin expression. Patients who had high survivin expression levels were at significantly increased risk of death from RCC compared with patients who had low expression levels (risk ratio [RR], 5.3; 95% confidence interval [95% CI], 3.5-7.9). The 5-year cancer-specific survival rate was 43.0% for patients with high survivin expression and 87.2% for patients with low survivin expression. In multivariate analysis, survivin expression remained associated with death from RCC even after adjusting for the Eastern Cooperative Oncology Group performance status; 2002 Tumor, Lymph Node, Metastases (TNM) stage groupings and nuclear grade (RR, 2.4; 95%CI, 1.5-3.8); and the Mayo Clinic composite TNM stage groupings, tumor size, nuclear grade, and tumor necrosis (SSIGN) score (RR, 1.8; 95%CI, 1.1-2.9). Among 273 patients who had localized ccRCC, survivin expression was associated significantly with cancer progression (RR, 3.9; 95%CI, 2.4-6.2). CONCLUSIONS: Survivin expression is an independent predictor of ccRCC progression and death from RCC. Thus, survivin has the potential to offer additional prognostic information and to provide a novel target for the development of new adjuvant therapies.

Aged↗

PubMed2006

B7-H4 expression in renal cell carcinoma and tumor vasculature: associations with cancer progression and survival.

B7-H4 is a recently described B7 family coregulatory ligand that has been implicated as an inhibitor of T cell-mediated immunity. Although expression of B7-H4 is typically limited to lymphoid cells, aberrant B7-H4 expression has also been reported in several human malignancies. To date, associations of B7-H4 with clinical outcomes for cancer patients are lacking. Therefore, we examined B7-H4 expression in fresh-frozen tumor specimens from 259 renal cell carcinoma (RCC) patients treated with nephrectomy between 2000 and 2003 and performed correlative outcome analyses. We report that 153 (59.1%) RCC tumor specimens exhibited B7-H4 staining and that tumor cell B7-H4 expression was associated with adverse clinical and pathologic features, including constitutional symptoms, tumor necrosis, and advanced tumor size, stage, and grade. Patients with tumors expressing B7-H4 were also three times more likely to die from RCC compared with patients lacking B7-H4 (risk ratio = 3.05; 95% confidence interval = 1.51-6.14; P = 0.002). Additionally, 211 (81.5%) specimens exhibited tumor vasculature endothelial B7-H4 expression, whereas only 6.5% of normal adjacent renal tissue vessels exhibited endothelial B7-H4 staining. Based on these findings, we conclude that B7-H4 has the potential to be a useful prognostic marker for patients with RCC. In addition, B7-H4 represents a target for attacking tumor cells as well as tumor neovasculature to facilitate immunotherapeutic treatment of RCC tumors. Last, we demonstrate that patients with RCC tumors expressing both B7-H4 and B7-H1 are at an even greater risk of death from RCC.

Aged↗

PubMed2006

Tumor B7-H1 is associated with poor prognosis in renal cell carcinoma patients with long-term follow-up.

B7-H1 participates in T-cell costimulation functioning as a negative regulator of immunity. Recent observations suggest that B7-H1 is expressed by renal cell carcinoma (RCC) tumor cells and is associated with poor prognosis. However, outcome analyses have been restricted to patients with fresh-frozen tissue and limited follow-up. We report the clinical effect of B7-H1 in RCC patients with a median of 10 years of follow-up. Between 1990 and 1994, 306 patients underwent nephrectomy for clear cell RCC and had paraffin tissue available for review. We did immunohistochemistry with anti-B7-H1 and conducted outcome analyses. Among the 306 patients, 73 (23.9%) harbored tumors with B7-H1 expression. Patients with tumor B7-H1 were at a significantly increased risk of both death from RCC [risk ratio (RR), 3.92; P < 0.001] and overall mortality (RR, 2.37; P < 0.001). The 5-year cancer-specific survival rates were 41.9% and 82.9% for patients with and without tumor B7-H1, respectively. In a multivariate model, tumor B7-H1 remained associated with cancer-specific death even after adjusting for tumor-node-metastasis stage, grade, and performance status (RR, 2.00; P = 0.003). In the subset of 268 patients with localized RCC, tumor B7-H1 was significantly associated with metastatic cancer progression (RR, 3.46; P < 0.001) and death from RCC (RR, 4.13; P < 0.001) even after adjusting for stage, grade, and performance status (RR, 1.78, P = 0.036). RCC patients with tumor B7-H1 are at significant risk of rapid cancer progression and accelerated rates of mortality. B7-H1 may function as a key determinant in RCC, abrogating immune responses directed against this immunogenic tumor.

Antigens, CD↗

PubMed2006

The preoperative erythrocyte sedimentation rate is an independent prognostic factor in renal cell carcinoma.

BACKGROUND: Prognostic nomograms are used increasingly in clinical trials and to guide surveillance for patients with renal cell carcinoma (RCC). An elevated erythrocyte sedimentation rate (ESR) reportedly has been associated with a poor prognosis among patients with RCC, but the ESR is not incorporated into existing nomograms. Hence, the current study was conducted to expand on prior observations pertaining to the ESR as a prognostic indicator in patients with RCC. METHODS: The authors identified 3008 patients who underwent nephrectomy for RCC between 1970 and 2002. Disease-specific survival was estimated using the Kaplan-Meier method, and its association with the ESR and other clinical and pathologic features was evaluated using Cox proportional hazards regression analysis. RESULTS: A preoperative ESR was available for 1075 patients (35.7%), 501 of whom (46.6%) exhibited an elevated ESR, including 437 of 881 patients (49.2%) with clear cell RCC, 41 of 134 patients (30.6%) with papillary RCC, and 20 of 48 patients (41.7%) with chromophobe RCC. An elevated ESR was associated with adverse clinical, laboratory, and pathologic profiles for all three histologic subtypes. The risk ratios (RRs) and 95% confidence intervals (95% CIs) for death because of clear cell RCC, papillary RCC, and chromophobe RCC for patients with an elevated ESR were 3.6 (95% CI, 1.1-1.9), 3.8 (95% CI, 1.4-10.6), and 10.3 (95% CI, 1.2-89.5), respectively. The association between an elevated ESR and death from clear cell RCC persisted even after multivariate analysis (RR of 1.5; 95% CI, 1.2-2.0). CONCLUSIONS: An elevated ESR in patients with RCC suggested the presence of aggressive disease and poorer outcomes after surgical treatment. For patients with clear cell RCC, the ESR provided useful information above and beyond traditional prognostic algorithms, and it may be valuable for preoperative prognostication.

Adult↗

PubMed2006

Second primary malignancies associated with renal cell carcinoma histological subtypes.

PURPOSE: 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. MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Carcinoma, Renal Cell↗

PubMed2006

The role of nephron sparing surgery for metastatic (pM1) renal cell carcinoma.

PURPOSE: Studies have demonstrated increased time to progression when cytoreductive nephrectomy is performed for metastatic renal cell carcinoma. We evaluated the role of nephron sparing surgery in these patients. MATERIALS AND METHODS: We selected all patients with pM1 renal cell carcinoma treated with nephron sparing surgery or radical nephrectomy, and all patients with pM0 renal cell carcinoma undergoing nephron sparing surgery for solitary kidney from 1970 to 2002 from the Mayo Clinic Nephrectomy Registry. RESULTS: We identified 16 patients who underwent nephron sparing surgery for pM1 renal cell carcinoma. Solitary kidney was present in 12, 3 had bilateral synchronous disease and 1 had elective nephron sparing surgery. Cancer specific survival rates at 1, 3 and 5 years were 81%, 49% and 49%, respectively. We identified 404 patients who underwent radical nephrectomy for pM1 renal cell carcinoma. Cancer specific survival rates at 1, 3 and 5 years were 51%, 21% and 13%, respectively. The pM1 nephron sparing surgery for solitary kidney cases were more likely to have early (33% vs 10%, p = 0.009) or late (50% vs 19%, p = 0.018) complications compared with pM1 radical nephrectomy cases. There were no significant differences in early (p = 0.475) or late (p = 0.350) complications between pM1 nephron sparing surgery cases and 139 pM0 nephron sparing surgery cases. CONCLUSIONS: Cancer specific survival rates in pM1 nephron sparing surgery cases were comparable to pM1 radical nephrectomy cases. Although there were differences in early and late complications between the pM1 nephron sparing surgery and pM1 radical nephrectomy groups, there were no differences when compared with imperative pM0 nephron sparing surgery cases. This study demonstrates that nephron sparing surgery can achieve adequate cytoreductive therapy while preserving renal function, with postoperative complication rates similar to those of pM0 nephron sparing surgery cases.

Aged↗

PubMed2006

Extranodal extension in regional lymph nodes is associated with outcome in patients with renal cell carcinoma.

PURPOSE: The 2002 American Joint Committee on Cancer pN classification for renal cell carcinoma is based on the number of positive regional lymph nodes. We examined the associations of pathological features of lymph node metastases with patient outcome to improve the prognostic accuracy of the current classification. MATERIALS AND METHODS: We studied the records of 2,076 patients treated with radical nephrectomy for unilateral, sporadic pM0 renal cell carcinoma between 1970 and 2000. There were 34 patients with metastasis in a single regional lymph node (pN1) and 35 with metastases in more than 1 lymph node (pN2). Pathological features of lymph node metastases, including the number and percent of positive lymph nodes, total number of lymph nodes removed, grade, necrosis, extranodal extension, and largest dimension and surface area of metastases were determined by 2 urological pathologists (HHD and JCC). RESULTS: There was no statistically significant association between the pN classification and death from renal cell carcinoma (pN2 vs pN1 RR 1.05, 95% CI 0.62 to 1.79, p = 0.846). However, patients with extranodal extension were twice as likely to die of renal cell carcinoma than patients in whom metastases did not extend outside of the lymph node capsule (RR 2.02, 95% CI 1.18 to 3.45, p = 0.010). The 5-year cancer specific survival rate was 18% and 35% in patients with and without extranodal extension, respectively. CONCLUSIONS: We believe that a pN classification based on the presence or absence of lymph node metastases with a notation regarding the presence or absence of extranodal extension represents a significant improvement in the prognostic accuracy of the current pN classification.

Carcinoma, Renal Cell↗

PubMed2006

Rare expression of KIT and absence of KIT mutations in high grade renal cell carcinoma.

PURPOSE: RCCs with sarcomatoid differentiation have been reported to frequently express KIT protein, suggesting that imatinib mesylate (STI-571 or Gleevectrade mark) may be effective treatment for these aggressive tumors. We determined the frequency of KIT expression and mutation in a large series of high grade RCCs. MATERIALS AND METHODS: We identified 194 patients who underwent nephrectomy for unilateral, sporadic nuclear grade 4 RCC between 1970 and 2002, including 123 with sarcomatoid differentiation. Sections from representative paraffin embedded tissue blocks were immunostained in an autostainer using ethylenediaminetetraacetic acid antigen retrieval, a polyclonal KIT antibody and the avidin-biotin peroxidase complex method. Mutational analysis was performed in all immunopositive and select negative cases by polymerase chain reaction amplification of KIT exons 9, 11, 13 and 17. RESULTS: Only 7 tumors (3.6%) showed KIT expression, including 5 of the 123 (4.1%) with sarcomatoid differentiation. Four of the 7 tumors showed focal staining only. No mutations were identified in the 7 positive cases or in 8 randomly selected negative samples. Death from RCC occurred in all 7 patients with KIT positive tumors at a median of 0.6 years (range 0.3 to 2.3) and in 139 of 187 with KIT negative tumors at a median of 0.8 years (range 0 to 10.2). CONCLUSIONS: KIT expression was identified in less than 5% of high grade RCCs with or without sarcomatoid differentiation but none of the tumors showed KIT mutations. These findings indicate that imatinib therapy is unlikely to be effective in patients with high grade RCC.

Carcinoma, Renal Cell↗

PubMed2006

Immunotherapy for prostate cancer.

The absence of curative therapies for advanced or recurrent forms of prostate cancer has prompted a vigorous search for novel treatment strategies. Immunotherapy encompasses one particularly promising systemic approach to treat prostate cancer. Immune-based strategies to treat prostate cancer have recently been facilitated by the identification of a number of prostate tissue/tumor antigens that can be targeted, either by antibody or T cells, to promote prostate tumor cell injury or death. These same prostate antigens can also be used for the construction of vaccines to induce prostate-specific T cell-mediated immunity. Greater insight into specific mechanisms that govern antigen-specific T cell activation has brought with it a number of innovative methods to induce and enhance T cell-mediated responses against prostate tumors. For instance, autologous dendritic cells loaded with prostate antigens have proved useful to induce prostate-specific T cell activation. Similarly, in vivo manipulations of the T cell costimulatory pathway receptors can greatly facilitate tumor-specific T cell activation and potentiate T cell-mediated responses against a number of malignancies, including prostate cancer. Therefore, in this review we summarize recent advances pertaining to immunotherapeutic approaches to treat prostate cancer.

Humans↗

PubMed2005

Costimulatory molecule B7-H1 in primary and metastatic clear cell renal cell carcinoma.

BACKGROUND: Cancer cell expression of costimulatory molecule B7-H1 has been implicated as a potent inhibitor of T-cell-mediated antitumoral immunity. The authors recently reported that B7-H1 is aberrantly expressed in primary renal cell carcinoma (RCC). Blockade of B7-H1, as demonstrated in several murine cancer models, now represents a promising therapeutic target in RCC. However, the potential expression of B7-H1 in metastatic RCC has not been investigated. In the current study, the authors updated their primary RCC results with additional follow-up and investigated the potential role of B7-H1 in metastatic RCC. METHODS: Between 2000 and 2004, 196 patients underwent nephrectomy and 26 patients had resection of RCC metastases for clear cell RCC. Immunohistochemical analysis was performed on tumor cryosections using a B7-H1 monoclonal antibody (clone 5H1). A urologic pathologist quantified the percentage of B7-H1-positive tumor cells and lymphocytes. RESULTS: Variable levels of B7-H1 were expressed on primary RCC tumor cells (n = 130 [66.3%]) and primary tumor-infiltrating lymphocytes (n = 115 [58.7%]). Patients with high expression of B7-H1 on primary tumor cells and/or lymphocytes were significantly more likely to die of RCC compared with patients with low B7-H1 expression (risk ratio [RR] = 4.17; 95% confidence interval [95% CI], 1.97-8.84; P < 0.001) and this risk persisted in multivariate analysis after adjusting for the Mayo Clinic stage, size, grade, and necrosis score (RR = 2.63; 96% CI, 1.23-5.64; P = 0.013). Of the 26 metastatic specimens, cancer cell and lymphocyte B7-H1 expression were demonstrated in 17 (65.4%) and 18 (69.2%) specimens, respectively. In total, 14 (54.3%) metastatic specimens had high aggregate B7-H1 levels compared with 44.4% in primary RCC specimens. CONCLUSIONS: Patients with RCC with high B7-H1 expression were significantly more likely to die even after multivariate analysis. The authors also demonstrated that a high percentage of RCC metastases similarly harbored B7-H1. The authors surmised that B7-H1 blockade may augment current immunotherapy, including patients treated for metastases after cytoreductive nephrectomy.

Antigens, CD↗

PubMed2005

Prostate cancer immunology: biology, therapeutics, and challenges.

A number of recently developed and promising approaches to antitumoral immunotherapy are being investigated as potential treatments for advanced prostate cancer. These approaches largely revolve around strategies to increase antigen-specific T-cell activation against prostate tumors as well as precise manipulations of critical co-regulatory receptors that help to maintain and prolong the activity of antigen-presenting cells and T cells that are capable of mediating tumor regression. Herein, we describe the experience with the most recent and promising approaches pertaining to prostate cancer immunotherapy. Additionally, we discuss the mechanistic basis for these approaches as well as current limitations that must still be addressed in order to propel immunotherapy into the forefront of prostate cancer treatment.

Humans↗

PubMed2005

Histologic coagulative tumor necrosis as a prognostic indicator of renal cell carcinoma aggressiveness.

BACKGROUND: Prognostic markers for renal cell carcinoma (RCC), such as patient symptoms, tumor stage, tumor size, and tumor grade, are useful for determining appropriate follow-up and selecting patients for adjuvant therapy. Histologic coagulative tumor necrosis, also reported to be a prognostic marker for RCC, has not previously been extensively described or investigated. Hence, the objective of the current study was to characterize tumor necrosis as a prognostic feature of RCC. METHODS: The authors of the current study identified 3009 patients treated surgically for RCC between 1970 and 2002 from the Mayo Clinic Nephrectomy Registry (Rochester, MN). Associations of tumor necrosis with clinical, laboratory, and pathologic features were examined with chi-square, Fisher exact test, and Wilcoxon rank-sum tests. Cancer-specific survival was estimated with the Kaplan-Meier method, and associations with outcome were assessed with Cox proportional hazard models. RESULTS: Tumor necrosis was present in 690 of 2445 (28%) clear cell, 196 of 421 (47%) papillary, and 28 of 143 (20%) chromophobe RCCs. The risk ratio for death from RCC in patients with necrotic compared with non-necrotic tumors was 5.27 (95% confidence interval [CI]: 4.56-6.09; P < 0.001) for clear cell, 4.20 (CI: 1.65-10.68; P < 0.001) for chromophobe, and 1.49 (CI: 0.81-2.74; P = 0.199) for papillary RCC. The survival difference for clear cell RCC persisted even after multivariate adjustment for tumor stage, size, and grade (risk ratio 1.90; P < 0.001). CONCLUSIONS: Histologic coagulative tumor necrosis is an independent predictor of outcome for clear cell and chromophobe RCC, and it should be routinely reported and used in clinical assessment.

Adenocarcinoma, Clear Cell↗

PubMed2005

Reclassification of patients with pT3 and pT4 renal cell carcinoma improves prognostic accuracy.

BACKGROUND: The significance of adrenal invasion and tumor thrombus in renal cell carcinoma (RCC) has been debated recently. The authors evaluated the associations of direct adrenal invasion, perinephric fat invasion, and tumor thrombus level with outcome to determine whether reclassification would improve the prognostic accuracy of the current primary tumor classification. METHODS: The authors studied 697 patients treated with nephrectomy for pT3 and pT4 RCC between 1970 and 2000. Associations with outcome were evaluated using Cox proportional hazards regression and prognostic accuracy was measured using the c index. RESULTS: Among patients with pT3 RCC, direct adrenal invasion was significantly associated with death from RCC (risk ratio, 2.11; P = 0.004). No significant difference in survival was found between patients with pT4 RCC and pT3 tumors with direct adrenal invasion (P = 0.490). Among patients with pT3b RCC, those with level I-III tumor thrombus were significantly more likely to die of RCC compared with patients harboring level 0 tumor thrombus (risk ratio, 1.62; P < 0.001). In addition, patients with fat invasion were more likely to die of RCC compared with pT3 patients without fat invasion (risk ratio, 1.87; P < 0.001). Therefore, patients with pT3 RCC were reclassified into 4 prognostic groups, and this reclassification significantly improved prediction of death from RCC compared with the current classification (c indices of 0.61 vs. 0.55, respectively). CONCLUSIONS: Direct adrenal invasion from RCC should be reclassified as pT4. In addition, the proposed reclassification for patients with pT3 RCC improved prognostic accuracy.

Adrenal Gland Neoplasms↗

PubMed2005

B7-H1 glycoprotein blockade: a novel strategy to enhance immunotherapy in patients with renal cell carcinoma.

Cancer cell expression of the B7-H1 glycoprotein has been implicated as a potent inhibitor of T cell-mediated antitumoral immunity. We recently reported that B7-H1 is aberrantly expressed in renal cell carcinoma (RCC) and suggested that blockade of B7-H1, as demonstrated in several murine cancer models, represents a promising therapeutic target in RCC. Herein, we update our results with tumor-associated B7-H1 and discuss future clinical applications. Between 2000 and 2002, 196 patients underwent nephrectomy for clear-cell RCC and had fresh-frozen tissue available for review. Immunohistochemical analysis was performed on tumor cryosections, and outcome was obtained from the Mayo Clinic Nephrectomy Registry (Rochester, MN). At last follow-up 38 of the 196 patients died of RCC. The median duration of follow-up for patients still alive was 2.7 years. Among the 196 RCC specimens, 130 (66.3%) demonstrated aberrant tumor-associated B7-H1 expression. Patients with tumor-associated B7-H1 expression were significantly more likely to die of RCC compared with patients whose specimens did not have aberrant tumor-associated B7-H1 expression (risk ratio, 3.34; 95% confidence interval [CI], 1.30 - 8.55; P = 0.012). This risk persisted in multivariate analysis even after adjusting for the Mayo Clinic SSIGN (stage, size, grade, and necrosis) score (risk ratio, 3.52; 95% CI, 1.35-9.15; P = 0.010). Tumor-associated B7-H1 expression is significantly associated with poor prognosis among patients with clear-cell RCC. Manipulation of B7-H1 with therapeutic intent remains a realistic and viable therapeutic option.

Antigens, CD↗