Immunoreactivity of p27(Kip1), cyclin D3, and Ki67 in conventional renal cell carcinoma.

The goal of the study was to evaluate expression of the cell-cycle regulatory proteins (p27(Kip1) and cyclin D3) and proliferation marker Ki67 in normal human kidneys and renal cell carcinoma (RCC) tissues. Intensity of the markers' expression was prospectively studied and compared between normal and RCC tissue samples. Association was analyzed with cancer clinical parameters. p27(Kip1) was significantly upregulated in normal compared with in RCC samples. Immunoreactivity of the protein negatively correlated with tumor size and was associated with pathological stage and grade. Patients with symptomatic disease had significantly less marker expression than those with incidentally discovered tumors. Intensity of Ki67 staining positively correlated with primary tumor size and associated with disease stage and grade. Cyclin D3 immunoreactivity positively correlated with tumor size. Loss of p27(Kip1) expression, pathological stage, grade, and tumor size were risk factors for disease recurrence (P = 0.0072, 0.0011, and 0.0467, and P < 0.0001, respectively) and patient death (P = 0.0021, 0.0106, 0.0151, and 0.0021, respectively). With Cox multivariate analysis loss of p27(Kip1) expression (hazard ratio 9.3, P = 0.002) and tumor size (hazard ratio 5.9, P = 0.015) were the predictors of cancer-specific survival. In conclusion, intensity of the markers' expression in RCC is associated with tumour clinical parameters (size, stage, grade, and disease presentation type). Loss of p27(Kip1) expression is a risk factor for the disease recurrence and cancer-related patient death.

Expression of p27((Kip1)), cyclin D3 and Ki67 in BPH, prostate cancer and hormone-treated prostate cancer cells.

p27((Kip1)), cyclin D3 and Ki67 are the markers of DNA damage and cell proliferation. The goal of the current study was to analyze expression of the markers in benign and malignant prostate cancer tissues. Activity of p27((Kip1)), cyclin D3 and Ki67 was immunohistochemically evaluated in different cells of BPH, prostate cancer (PCa) and hormonally treated prostate cancer (HTPCa) tissues. The tissue samples were derived by means of TURP or radical prostatectomy. Intensity of the expression was compared between the groups, and association was sought with clinical parameters. Total expression of p27((Kip1)) was significantly higher in BPH as compared with PCa. Epithelial marker expression was higher in HTPCa than in PCa. Intensity of the expression in epithelial, vascular and ductal cells was negatively associated with the tumor stage and Gleason grades. Total Ki67 activity was positively correlated with patient age and serum PSA level. There was significantly higher expression in PCa and hormone-escaped PCa (HEPCa) as compared with BPH. Epithelial and vascular marker expression was positively associated with tumor stage and Gleason grades. There was a positive correlation between cyclin D3 and serum PSA level. With the increase of Gleason grades, cyclin D3 expression increased significantly. Expression of p27((Kip1)) negatively correlated with Ki67 and cyclin D3, while the latter two markers correlated positively. p27((Kip1)) is down-regulated, whereas Ki67 and cyclin D3 are up-regulated in PCa. Intensity of the markers' expression is associated with tumor stage and grades. Hormonotherapy of PCa causes activation of p27((Kip1)). HEPCa is characterized by increased Ki67 expression.

Is ultrasound of the retroperitoneum a valuable staging method in selecting testicular cancer patients for primary retroperitoneal lymph node dissection?

OBJECTIVE: In nonseminomatous testicular cancer patients with normal serum tumor markers and no distant metastasis, postorchiectomy surgery is a valid treatment option if the disease extension into the retroperitoneum is not advanced. We assessed the ability of ultrasound (US) to exclude the presence of bulky retroperitoneal disease. MATERIALS AND METHODS: One hundred and forty testicular cancer patients underwent US and computed tomography (CT) of the retroperitoneum. US results were analyzed using three cutoffs: 5 cm (conventional staging), 3 cm (based on the minimal sonographical dimension of actual bulky disease) and 0 cm ('clean retroperitoneum' or any detectable nodes), and were compared with CT data using the 5-cm cutoff ('gold standard'). RESULTS: The sensitivity, specificity, overall accuracy, positive and negative predictive values of US in detecting of bulky retroperitoneum for the 5-cm cutoff were 83, 96, 93, 88 and 94%, for the 3-cm cutoff 100, 91, 94, 80 and 100%, and for the 0-cm cutoff 100, 66, 74, 49 and 100%, respectively. CONCLUSIONS: In stage I and IIA/B marker-negative nonseminomas if the treatment strategy is surgery, US may facilitate the selection process; the report of a clean retroperitoneum safely excludes the presence of bulky disease and may be an indication for lymphadenectomy, although in case of positive findings a CT should be performed.

Loss of p27(Kip1) CDKI is a predictor of poor recurrence-free and cancer-specific survival in patients with renal cancer.

The importance of cyclin-dependent kinase inhibitors (CDKI) in benign and malignant urological diseases is a subject of intense ongoing investigation. The goal of the current study was to analyze the expression of p27((Kip1))CDKI in benign and malignant renal cells and assess their possible association with different clinical parameters. Expression of p27((Kip1)) was evaluated and compared in 24 normal human kidneys and in 52 renal cell carcinoma (RCC) tissue samples. Intensity of the expression was compared between the groups and association was analyzed with cancer clinical parameters. The expression of the marker was significantly higher in normal than in RCC samples (P = 0.0045). Intensity of p27((Kip1)) expression in RCC was negatively correlated with tumor size (Rho = -0.438, P = 0.0051) and associated with pathological stage and grade (P = 0.0488 and < 0.0001, respectively). The patients with symptomatic disease had significantly less marker expression than incidentally discovered tumors (P = 0.0301). Loss of p27((Kip1)) expression, pathological stage, grade and tumor size were the risk-factors for disease recurrence (P = 0.0072, 0.0011, 0.0467 and < 0.0001, respectively) and patient survival (P = 0.0021, 0.0106, 0.0151 and 0.0021, respectively). With Cox multivariate analysis loss of p27((Kip1)) expression (hazard ratio 9.3, P = 0.002) and tumor size (hazard ratio 5.9, P = 0.015) were the predictors of cancer-specific survival. Expression of p27((Kip1)) is significantly decreased in RCC as compared with normal kidney tissue. Intensity of the expression is associated with clinical parameters: tumor size, stage, grade and disease presentation. Loss of p27((Kip1)) expression is a risk-factor for disease recurrence and the strongest predictor of cancer-specific survival.

Three cycles of etoposide and cisplatin chemotherapy in clinical stage IS nonseminomatous testicular cancer.

PURPOSE: To assess the efficacy of three cycles of etoposide and cisplatin (EP) chemotherapy in the patients with serological disease only after orchiectomy. MATERIALS AND METHODS: Fifteen patients with nonseminomatous germ cell tumors of the testis and elevated serum tumor markers as the only evidence of persistent disease following radical orchiectomy (clinical stage IS cancer), were treated at our institution from March 1995 to February 2003. All patients received three cycles of EP chemotherapy. The toxicity was compared with that in control group consisting of 93 patients treated with three standard cycles of cisplatin, etoposide and bleomycin for good-prognosis metastatic diseases. RESULTS: The markers normalized in all patients after one (in 11 cases) or two (in 4 cases) cycles. One patient required subsequent surgery for recurrent retroperitoneal mature teratoma. All patients remained disease-free during the median follow-up period of 85 months (range: 33-128). In patients receiving EP chemotherapy less number of treatment cycles was associated with grade IV leukopenia compared to control group (p=0.04). CONCLUSIONS: A treatment program that consists of three cycles of EP caused complete disease control in all patients. The applied regimen may be considered as a therapeutic option with reduced toxicity in clinical stage IS nonseminomatous testicular cancer patients. More evidence, however, needs to be accumulated.

Retroperitoneal lymph node dissection for high-risk stage I and stage IIA seminoma.

INTRODUCTION: The clinical results of radiotherapy in low-stage seminoma are excellent with negligible early morbidity. However, in a long-term follow-up various complications may occur. On the other hand, experience in nonseminomas shows that surgical morbidity has decreased markedly after invention of a nerve-sparing technique. These issues served as a rationale for us to perform the primary retroperitoneal lymph node dissection (RPLND) in seminoma patients. MATERIALS AND METHODS: Fourteen pure seminoma patients (10 high-risk stage I and four with clinical stage IIA) underwent nerve-sparing RPLND from September, 1997 to December, 2002. RESULTS: Pathological evaluation revealed lymph node involvement in three out of 10 clinical stage I and in all four stage IIA cases. The patients' acceptance of the surgery was good. Minor intra- and early postoperative complications were observed in two cases. Antegrade ejaculation was preserved in all patients. No retroperitoneal or distant recurrences have been observed. All patients were free of disease with the mean follow-up period of 56 months. CONCLUSION: The excellent results and minimum morbidity of nerve-sparing RPLND together with the increased concerns on late complications of radiotherapy may turn the preference of surgery in low-stage seminoma into the subject of future discussion.

One cycle of bleomycin, etoposide and cisplatin plus two cycles of etopeside and cisplatin chemotherapy in selected patients with low-volume stage II nonseminomatous germ cell tumor of the testis.

OBJECTIVE: To assess the feasibility of bleomycin omission from second and third cycles of bleomycin, etoposide and cisplatin (BEP) chemotherapy in low-volume stage II nonseminomatous germ cell tumor patients who achieve a normal tumor marker level after the first cycle of treatment. MATERIALS AND METHODS: Out of 59 nonseminomatous testicular cancer patients with low-volume retroperitoneal disease, serum markers normalized after the first cycle of treatment in 30 cases. 12 patients completed 3BEP (group 1; years 1994-1998) and other 18 patients received etoposide and cisplatin (EP) as second and third cycles of chemotherapy (group 2; years 1998-2004). RESULTS: All patients from each group achieved complete response with chemotherapy alone or by subsequent resection of teratoma or necrosis. There was no relapse with active cancer after the treatment. All patients remained disease-free during the median follow-up period of 97 and 48 months for groups 1 and 2 respectively. CONCLUSIONS: One cycle of BEP plus two cycles of EP chemotherapy was as effective as three standard cycles of BEP. The regimen can be suggested as a less toxic therapeutic alternative in these selected patients. More cases, however, in a prospective randomized setting are required to further verify these data.