Microsatellite allelotyping differentiates chromophobe renal cell carcinomas from renal oncocytomas and identifies new genetic changes.

AIMS: The diagnosis of renal oncocytomas (ROs) and chromophobe renal cell carcinomas (RCCs) based on histological features is often uncertain. To assess the value of genetic analysis in their differential diagnosis we analysed 27 ROs and 21 chromophobe RCCs by microsatellite allelotyping. METHODS AND RESULTS: Markers at the short and long arms of chromosomes specifically involved in the genetic changes of the four main types of renal cancers were selected. Allelic changes were identified by automated sequencing. Allelic changes at chromosome 1p occurred in 8/26 (31%) and at chromosome 14q in 4/27 (15%) ROs. Loss of heterozygosity (LOH) at chromosomes 1, 2, 6, 10, 13, 17 and 21 were seen in 90%, 90%, 96%, 86%, 85%, 90% and 72% of the chromophobe RCCs, respectively. Alterations of at least three of these chromosomal sites were detected in each chromophobe RCC. In addition, we found recurrent LOH at chromosomes 9p23 (43%), 18q22 (30%), 5q22 (28%) and 8p (28%) in chromophobe RCCs. CONCLUSIONS: Chromophobe RCCs can be differentiated from ROs by analysing specific chromosomal regions with microsatellites.

Prognostic histological and immune markers of renal cell carcinoma.

Recent development on the fields of molecular genetics and immunology of human renal cell carcinoma (RCC) have resulted in more successful treatment of advanced and metastatic RCCs. Re-evaluation of the prognostic/predictive data aim the initial tumor staging of RCC patients to achieve better patient selection for immune and gene therapy. 125 RCC patients diagnosed according to the Heidelberg histological classification, graded, Robson staged, immune treated (Interferon-a a+ Vinblastine or Broncho-Waxom/Decaris) were followed-up clinically for 36 months. Tumor immunity markers by immunohistochemistry of tumor infiltrating lymphocytes (TIL) were detected by immunoperoxidase methods using monoclonal antibodies. Tumoral immune complexes (TIC) were visualized by fluorescent polyclonal antibodies. Histologically oncocytomas defined a better (p<0.02) and sarcomatous RCCs a worse (p<0.01) follow-up prognosis. Basically, the metastatic status (related with the stage and grade) determined the clinical outcome (p<0.00002) of the RCC patients. Tumoral immune complexes (TIC) were weak positive, while tumor infiltrating lymphocytes (TIL) weak negative predictors of the succes of Broncho-Waxom/Decaris immune therapy. Molecular genetic based histological classification, grade, stage and metastatic status parameters together with some tumor immunity parameters (TIL, TIC) can predict the success of immunotherapy of RCC patients.

Specific von Hippel-Lindau protein expression of clear cell renal cell carcinoma with "immunogenic" features.

Human clear cell renal cell carcinoma (CCRCC) is characterized by specific von Hippel-Lindau (VHL) gene alterations and immunogenic features. In the present study, the immunohistochemical expression of the von Hippel-Lindau gene protein (pVHL) was compared with the presence of major histocompatibility complex (MHC I-II), tumor infiltrating lymphocytes (TIL) and tumoral immune complexes (TIC) in CCRCC. Native tumor tissues of 132 RCC patients (95 with the common clear cell subtype), diagnosed according to the Heidelberg classification, were obtained for immunohistochemistry. Tumor stainings with pVHL, MHC I-II and tumor infiltrating lymphocytes (T and B lymphocytes, monocytes) were detected by immunoperoxidase methods using monoclonal antibodies. Tumoral immune complexes (IgG, IgA, IgM and C1q, C3 complement proteins) were visualized by fluorescent polyclonal antibodies. Immune stainings were semiquantitatively evaluated. Specificity and sensitivity of these markers in relation to the common histological subtype of RCC (CCRCC) were calculated. CCRCC was characterized by specific pVHL expression. At the same time, CCRCC was associated with constitutional MHC I-II expression and highly specific degree of TIL and TIC. It is concluded that specific pVHL expression of CCRCC is frequently associated with immunogenic features. Immunohistochemical analysis aims the initial tumor staging of RCC patients to achieve better patient selection for immunotherapy. However, the association of pVHL expression with the immunogenic CCRCC is statistically relevant, the mechanism and its clinical relevance in immunotherapy still remains to be tested.

Renal cell carcinoma and paraneoplastic IgA nephropathy.

Paraneoplastic nephropathy is rarely associated with human tumors. Little is known about the pathogenetic background of this relationship. To our knowledge, no conclusive study of the association of potentially 'immunogenic' renal cell carcinoma (RCC) and paraneoplastic nephropathy has been published. For this reason, we performed an immunohistochemical analysis of native resected kidneys of 60 patients with RCC, paying special attention to their pre- and postoperative records. Sixteen (27%) of the 60 tumor patients had immune complex nephropathy (11 IgA nephropathy [IgA NP] and 5 focal segmental glomerulosclerosis [FSGS]). Preoperative proteinuria and/or hematuria observed in 11 of 16 cases disappeared in 6 IgA NP patients within a 2- to 3-month follow-up after nephrectomy. Eleven of 16 tumors stained with the anti human immunoglobulin (IgA or IgM) of the same isotype as that present in glomerular immune complexes. In 3 IgA NP patients RCC-associated von Hippel-Lindau (VHL) protein and IgA staining were found simultaneously in the tumor and glomeruli, with the clinical and laboratory findings disappearing after nephrectomy. Immune injury of the glomeruli due to a tumor-induced antigen-antibody response was demonstrated in these 3 IgA NP patients.

[Paraneoplastic nephropathy associated with adult renal carcinoma (immunologic and clinicopathologic study)]. / A felnöttkori vesecarcinomát kísérö paraneoplasiás nephropathia (immunológiai és klinikopatológiai tanulmány).

Rare "paraneoplastic nephropathies" are associated with a wide variety of human tumors. Little is known about the pathogenetical background. To our knowledge no systematic study about the association of potentially "immunogenic" renal cell cancer (RCC) and "paraneoplastic nephropathy" has been published so far. An immunohistochemical analysis of native kidneys and a nephrological follow up of 60 patients with renal cell cancer (RCC) treated at the Department of Urology, medical University, Pécs (Hungary) between 1993-1998 has been performed. Cellular and humoral immunity was analysed by immunohistochemistry. Clinical/laboratory parameters of the patients with tumor associated nephropathy were pre- and postoperatively registered. Eleven IgA-nephropathy (IgA-NP) and 5 focal segmental glomerulosclerosis (FSGS), manifested in preoperative clinical signs in 11 out of 16 cases were found. Clinical symptoms disappeared in 6 out of 8 IgA-NP patients by tumor nephrectomy in a follow up of 38.7 (18-51) months. Eleven out of 16 tumors were stained with the identical anti human immunoglobulin (IgA or IgM) present in the glomerular immune complexes. The RCC-associated VHL (von Hippel-Lindau) protein was detectable in 3 out of 8 IgA-NP patients as an antigen component of their nephritogenic immune complexes. Tumor infiltrating lymphocytes (TIL) considered as a local sign of cellular tumor immunity were more frequently present in tumors associated with nephropathy than without it (69% vs 25%). Pathogenetic correlation between the tumor immunity in renal cell carcinoma and "paraneoplastic IgA-nephropathy" has been demonstrated in some of the cases. Tumor nephrectomy excluding the need of post-operative single kidney biopsies should be a safe tool in the differential diagnosis of tumor-associated nephrological conditions.

[Results of ambulatory mono- and combined interferon therapy in advanced kidney tumors]. / Ambulanter végzett interferon mono- és kombinációs terápia eredménye elórehaladott vesedaganat esetén.

The authors summarized their experiences during interferon alpha 2b treatment for RCC of advanced stage with special respect to the changes in general condition of patients. Since 1991 ambulantory interferon treatment was carried out on 35 patients. An account is given about the observations on treatment of 31 patients from this a group. After setting up three treatment-groups 4 patients received monotherapy, alpha interferon 2b subcutaneous injection in the first 3 days of the week, in 6-10 mill.i.u.dose. In combination with alpha interferon treatment 7 patients received a daily dose of 500 mg of medroxyprogesteron acetate, while in 20 cases 0.1 mg/body weight vinblastin infusion was given every three weeks with combination of alpha interferon treatment. In four cases complete (CR), in 5 cases partial remission was achieved (PR) while 10 patient remained in an unchanged state (NC). In 12 cases progression can be experienced. Ten patients died during the observation period. The clinical response time was 15 months (3-26), the remission period was in an average 9 months (5-14) and the remission rate (CR + PR) was 29% (31/9). According to the authors, the interferon treatment, despite its significant side effects, can be considered important and remarkable treatment.

Immunohistochemistry of complement response on human renal cell carcinoma biopsies.

The goal of the study was to characterize the complement humoral and cellular antitumor responses on primary renal cell carcinoma biopsies. As an original observation, complement activation was found on 11/22 cases. Classical complement pathway activation was characterized by tumor C1q complement protein and IgG deposition (5/22 cases). Alternative or nonimmune complement pathway activation was seen as tissue deposition of C3 (6/22 cases). The membrane attack complex was present in cases with alternative complement pathway activation at the sites of tumor necrosis. Renal cell carcinomas with complement activation overexpressed at least one of the complement regulatory factors (membrane cofactor protein, decay accelerating factor, membrane attack complex inhibitor) and major histocompatibility complex class II molecules. Tumor infiltrating lymphocytes were present in most of the renal cell carcinomas with complement activation (8/11). However, the number of tumor-infiltrating lymphocytes was correlated with the intensity of major histo-compatibility complex-II expression in 18/22 cases. Detection of complement activation and immune cell infiltrates on renal cell carcinoma primary biopsies may serve as a new predictive factor for immunotherapy.

Renal angiomyolipoma: report of three cases with regional lymph node involvement and/or with renal cell carcinoma.

AIMS AND BACKGROUND: Angiomyolipomas (AMLs) are benign hamartoid tumors which frequently occur in tuberous sclerosis (TS). They may be manifest at different organ sites such as kidneys, lymph nodes, liver and lung and may be associated with renal cell carcinoma (RCC). The nature of multiple organ involvement in AML (metastasis versus multicentric synchronous tumors), the malignant transformation and the relation of AML to RCC have not been sufficiently clarified. STUDY DESIGN: Three cases of renal AMLs in patients with tuberous sclerosis associated with lymphangioleiomyomatosis of the paraaortic lymph nodes and/or with RCC are reported. The concise clinical history of the patients as well as the findings of histology, immunohistochemistry and quantitative DNA analysis are presented. RESULTS: The multicentric form of AML and coincidence of renal AML and RCC were observed in 2 patients. AML and RCC were found within the same focus in one of the cases. RCCs were either aneuploid or "near diploid", whereas one of the multicentric AMLs showed a discordant DNA ploidy pattern, namely aneuploidy in the kidney and diploidy in the lymph nodes. CONCLUSIONS: The presented cases (all of them underwent periaortic lymphadenectomy) suggest that lymph node involvement in renal AML may be more frequent than expected (1-2% of all AMLs) on the basis of the few reported cases. The discordant DNA ploidy (renal versus lymph node lesions) observed in one of the cases with multicentric AML implies synchronous tumor growth at different sites rather than metastatic disease. The intimate coexistance of RCC and AML (RCC revealed by immunohistochemistry within a larger mass of renal AML) may indicate that malignant transformation of an AML should only be accepted, if such a coincidence is unequivocally excluded.

Catheter types and their abdominal implantation in peritoneal dialysis.

In the period 1976-1990 a total of 282 chronic uraemic patients were put to peritoneal dialysis by means of abdominally implanted Tenckhoff catheters, out of which 170 had to be replaced. Description of the catheter types is followed by a summary of the rules of surgical implantation and postoperative treatment that should be observed for the peritoneal dialysis to be effective. Discussed are the causes and percentage distribution of changes that call for catheter replacement, finally the alternatives of conservative therapy.

[Complications of peritoneal dialysis: sclerosing peritonitis]. / A peritonealis dialízis szövödménye: a sclerotizáló peritonitis.

One chronic uraemic patient was treated with intermittent peritoneal dialysis. During the 9th month decreasing of ultrafiltration and increasing of the blood level of low-molecular weight substances was observed. Laparotomy was performed twice because of increased intraperitoneal bleeding. During the operation peritoneal thickening, intestinal adhesion and diffuse bleeding was noticed. The patient died because of ileus. The most probable cause of sclerosing peritonitis was due to the formalin solution, which was used for the disinfection of the Tenckhoff catheter. The causes and prevention of sclerosing peritonitis has been summarised.

Sclerosing peritonitis caused by disinfectant in a patient under peritoneal dialysis.

An uraemic patient under intermittent peritoneal dialysis was found in the 9th month of treatment to present ultrafiltration drop and increase of low-molecular weight substances. Two instances of laparotomy for heavy abdominal bleeding revealed peritoneal thickening, laminar intestinal concrescence and diffuse haemorrhage. The patient died in the 13th month of treatment under symptoms of ileus. Other reasons excluded, sclerosing peritonitis was attributed to the formalin solution employed as disinfectant for the abdominal catheter. The causative factors are listed together with the chances of prevention.