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A blastema-associated antigen (BLA-1) was detected using a monoclonal antibody against malignant blastema from a Wilms' tumor. The localization of BLA-1 was investigated in a series of nine Wilms' cases, five fetal, one childhood, and two adult kidneys. In this series, BLA-1 antibody consistently stained cell surfaces of all Wilms' tumors containing blastemal components. The same staining pattern was maintained in tumors grown as heterotransplants in nude mice. The expression of BLA-1 antigen was examined in normal blastema of fetal kidneys. BLA-1 was immunolocalized to condensed blastemal cells in the nephrogenic zone throughout gestation. In addition, kidney samples from a young child or adults contained no blastemal cells and therefore showed no blastemal cell surface staining. Glomerular mesangial cell staining was demonstrated in kidneys from 12 weeks of gestation through adulthood. This staining in developing and mature glomeruli implies that mesangial cells may be derived from condensed blastemal cells. The finding of a cell surface antigen common to Wilms' blastema, fetal blastema, and mesangial cells has not been previously demonstrated.

A unilateral cystic renal process discovered prenatally was removed in a neonate. Dysplastic cysts were associated with diffuse (both intra- and perilobar) nephroblastomatosis. We describe a comprehensive immunohistological study confirming the transition observed on simple histology between the different structures: nephrogenic rests (CD9+, CD24+/-, CD56+/-), glomeruloid bodies (CD10++, CD35++), ducts lined by columnar epithelium (CD9+, CD24+, CD56++), cysts lined by cuboidal or thin epithelium (some cells CD10+, CD26+, others EMA+, CD24+). Although no typical S-shaped bodies are seen, small cysts and ducts with a columnar epithelium are considered similar. The dysplastic primitive ducts are KL1++, vimentin+/-, CD9+, CD24+. With a view to assessing dysplastic preneoplastic potential, the value of CD56 and Ki67 as activation antigens with possible prognostic significance is discussed.

IgG, IgA and IgM levels were examined in children treated for different malignant tumors. Chemotherapy decreased IgG and mainly IgM. There was increased incidence of infectious complications in IgG deficiency.

The localization of Thy-1, a surface membrane lipoglycoprotein, was investigated using a monoclonal antibody specific for human Thy-1 (HB-2S-1). The localization of Thy-1 during development was established in a series of five fetal, three childhood, and two adult normal kidneys. In this series, Thy-1 immunolocalization progressed from mesangial and endothelial cell staining in the 16- to 17-week fetuses to similar staining along with staining of the parietal epithelium of the capsule and proximal tubule staining in the 20- to 24-week fetuses. Glomerular mesangial cell and endothelial cell staining was absent by 9 months postnatally when the adult pattern of staining was apparent. The localization of Thy-1 during development was also compared with a series of pediatric renal tumors including 14 Wilms' tumors, 3 congenital mesoblastic nephromas, 1 clear cell sarcoma, and 1 pediatric renal cell carcinoma. Thy-1 staining was demonstrated in epithelial tubules of Wilms' tumors and in the spindle-shaped cells of congenital mesoblastic nephroma correlating with Thy-1 immunoreactivity in the kidney proximal tubule and fetal medullary stroma, respectively. Thy-1 staining was absent in the anaplastic epithelial Wilms' tumor, the renal cell carcinoma, and the clear cell sarcoma. This staining pattern fails to provide evidence that these tumors may arise from the medullary mesenchyme or the differentiated proximal convoluted tubule. These results show that Thy-1 is a renal differentiation marker and is useful in the characterization of tumors of renal development.

The expression of gamma/delta T cell antigen receptors (TcR) in T cell lines or clones derived from tumor-infiltrating lymphocytes (TIL) from patients with solid tumors was investigated. gamma/delta TcR T cell lines were derived from TIL from patients with Wilms tumor, sarcoma or metastatic melanoma by stimulation with autologous tumor cells alone and recombinant interleukin 2 and they exhibited nonspecific cytotoxicity against autologous and allogeneic tumor cells, or cells of the K562 or the MEL21 tumor cell lines. Two T cell lines were derived from a patient with Wilms tumor. One of them expressed a non-disulfide-linked gamma/delta TcR using the 60-kDa gamma chain, whereas, the other expressed a disulfide-linked gamma/delta TcR. A T cell line was derived from a patient with sarcoma and expressed a disulfide-linked gamma/delta TcR, whereas, a T cell line derived from a patient with melanoma expressed a non-disulfide-linked gamma chain of 62 kDa. Several T cell clones were developed from patients with metastatic melanoma or Wilms tumor and expressed either disulfide- or non-disulfide-linked gamma/delta TcR. Northern analysis of RNA from certain of these clones revealed a full-length gamma chain transcript, whereas, the alpha or beta chain transcripts were either absent or truncated. These T cell clones exhibited nonspecific cytotoxicity. Both disulfide- and non-disulfide-linked TIL T cell lines and clones expressed the delta TCS1 determinant. gamma/delta TcR+ cells in freshly prepared TIL from these patients were present in low proportions (less than 5%) and their delta TCS1/delta 1 ratios were within the range observed in the peripheral blood of normal donors. These results demonstrate that both disulfide- and non-disulfide-linked gamma/delta TcR are expressed on T cell lines and clones derived from TIL from solid tumors. Non-disulfide-linked gamma/delta TcR using the 56-66-kDa gamma chain are frequently found on TIL-derived T cell lines and clones. These 56-66-kDa gamma chains are rarely expressed on T cell lines or clones derived from peripheral blood lymphocytes of normal donors.

Tumour-infiltrating lymphocytes (TIL) of paediatric tumours obtained from 37 lesions of different histotype (12 osteosarcomas, 5 Wilms' tumours, 7 soft-tissue sarcomas, 5 neuroblastomas and 8 miscellaneous) were studied to establish their potential for therapy. Fresh isolated TIL were cultured for the first 2 weeks with low doses of interleukin-2 (IL-2) (20 Cetus U/ml) to select for "tumour-specific" lymphocytes potentially present in the neoplastic lesion, followed by culture with high doses of IL-2 (1000 Cetus U/ml) to achieve TIL expansion. TIL were grown with more than 10-fold expansion in only 9 cases (mean expansion: 58-fold, range 13.5-346). In 17 cases no viable cells were obtained. After 30 days of culture with IL-2 the proliferative ability of TIL declined sharply in the majority of cases and TIL became refractory to any further stimulus, including addition of IL-4, tumour necrosis factor alpha (TNF alpha) or interferon gamma, and activation with OKT3 in solid phase. In 20 out of 37 cases TIL were available for phenotypic and functional analysis. TIL after long-term culture were predominantly CD3+ but 2 cases of osteosarcoma showed a predominance of CD3+TcR gamma/delta cells. The CD4/CD8 ratio was more than 1 in 10 cases, without correlation with tumour histology, site of lesion or TIL growth. The number of CD16+ and CD25+ lymphocytes decreased progressively during culture, the latter concomitantly with a reduction of TIL growth rate. The lytic pattern of TIL against allogenic and autologous tumour (Auto-Tu) cells was variable, but specific lysis of Auto-Tu was seen in only one case (Wilms' tumour) after culture with TNF alpha and irradiated Auto-Tu cells. The immunohistochemical analysis of tumour lesions revealed a limited lymphocyte infiltrate, a low expression of histocompatibility leukocyte antigens (HLA) class I and of the adhesion molecules ICAM1, LFA3, and a significant production of transforming growth factor beta (TGF beta). These data indicate that TIL obtained from paediatric patients are difficult to expand at levels required for immunotherapy and lack a significant number of tumour-specific T lymphocytes. A low expression of immunomodulatory molecules on tumour cells or the production of suppressive factors may prevent activation and expansion of TIL in paediatric tumours.

HMB-45 (melanocytic cell-specific monoclonal antibody) immunoreactivity was investigated in 10 cases of angiomyolipoma (AML) (1 with massive regional lymph node involvement) of the kidney and detected in all of them. No HMB-45 immunoreactivity was found in other tumors of the region which can occasionally be confused with AML, such as renal cell carcinoma, Wilms' tumor, and retroperitoneal sarcoma (leiomyosarcoma and liposarcoma). These findings indicate that HMB-45 is not a melanocyte-restricted marker and suggest that its expression might be useful in distinguishing AML from other tumors of the kidney and retroperitoneum.

Using an indirect immunoperoxidase technique, we tested frozen specimens from 12 Wilms' tumors with monoclonal antibodies (MoAbs) reacting against a large panel of molecules including laminin, fibronectin, cytokeratin, vimentin, villin, CD24, CALLA/CD10, CR1, CD26, class I and class II major histocompatibility complex (MHC) molecules, and endothelium factor VIII. These molecules were chosen because they are markers of specific segments of the mature kidney and because their loss or acquisition is indicative of different steps of human nephrogenesis. KI67 MoAb was used to evaluate the proliferating activity of the cells. The blastemal component (cell compact areas) of Wilms' tumors consisted of vimentin-positive cells with a fibronectin network. However, signs of epithelial maturation were present in compact areas where cytokeratin-positive cells producing laminin were observed. The cells exhibited a high degree of proliferating activity. The tubule formations consisted of cytokeratin-positive cells and had a defined laminin border. All the cells, whether in compact areas or in tubules, were strongly CD24-positive. Some tubular formations showed signs of proximal maturation with the presence of CALLA, CD26, and even villin. In four cases class I-MHC molecules were expressed by some tubular cells. Large cystic cavities present in five cases were edged by cytokeratin, CD24-positive cells, or by vimentin, CALLA, CR1-positive cells. Some glomeruloid bodies, present in two cases, were also composed of vimentin, CALLA, and CR1-positive cells which correspond to the mature podocyte phenotype. The interstitial tissue contained mainly laminin and fibronectin network with macrophages and few CD3 lymphocytes. The presence of large cells with muscular differentiation was noted; round vimentin and CD26-positive cells were also seen. The endothelial cells of the vessels exhibited vimentin, factor VIII, and class I and class II MHC molecules as do mature cells, but in some cases the endothelial cells lacked class II molecule expression and were CALLA-positive. These results which confirmed and extended those previously described show that cell differentiation in Wilms' tumor mimics that observed during metanephros development. Moreover, this study shows that tumoral cells in nephroblastoma share several antigens with cells from lymphoid lineage (CD24, CALLA, and CD26) as do developing and mature kidney cells. Such cell phenotype dissection provides a useful and reliable tool for testing the influence of various factors on the development of hetero-transplanted or cultured Wilms' tumors.

Fifty-six primary childhood renal tumours, 14 normal and 12 fetal kidneys were examined for their staining reaction with xenogeneic anti-Wilms' antiserum. The antiserum was raised by injecting Wilms' tumour extracts into 6-month-old rabbits which had been rendered tolerant in utero with pooled normal kidney extracts. Renal carcinomas, mesoblastic nephroma and a large proportion of tubular wilms' tumours were stained by the antiserum. In contrast, 6 of 7 bone-metastasising renal tumours of childhood (BMRTC) failed to fluoresce when treated with the antiserum, suggesting that the BMRTC has a different origin from the other childhood renal tumours studied.

The carbohydrate antigen termed Lex (Gal beta 1----4[Fuc alpha 1----3]GlcNAc beta 1----R), its di- or trimeric form, and their sialylated antigens have been characterized as developmentally regulated, tumor-associated antigens in human gastrointestinal epithelia. In this paper, remarkable changes of these antigens, defined by respective monoclonal antibodies FH3, FH4, and FH6, in fetal kidney (mesonephros and metanephros) and other urogenital organs, as well as in various types of kidney tumors, have been investigated. During the development of each organ and tissue, the antigens were found to be maximally expressed at a defined period of organogenesis, and a shifting of expression from one locus to another was observed. Each antigen showed a slightly but clearly different stage of maximum expression. The following changes in metanephros development are of particular interest. Expression of the antigen defined by FH3 followed by the antigen defined by FH4 appeared only after six weeks of gestation in the convoluted tubuli at the central region of metanephros, and propagated rapidly into those at the peripheral cortex region with a simultaneous regression at the central region. The regression of FH4 antigen was more rapid than that of FH3. All three antigens were expressed in the medullar thin tubuli, which develop into the thin-limb of Henle's loop, in which only the antigens defined by FH3 and FH4 persisted and FH6 antigen disappeared. Well-differentiated, but not undifferentiated, renal adenocarcinomas strongly expressed the antigens defined by FH4 and FH6, although the antigen defined by FH6 was expressed in more differentiated tumor cells than the antigen defined by FH4. Well-differentiated cells organized into tubular structures showed a strong expression of these differentiation antigens. However, some tumor cells that were organized into tubular structures, but were characterized by undifferentiated cytomorphology (larger nucleus and smaller volume of cytoplasm), did not express FH4 and FH6 antigens. Thus, cytodifferentiation and histotypic differentiation proceed independently within kidney tumors. The fucosylated type 2 chain structures defined by these three monoclonal antibodies are useful markers that indicate the degree of tumor differentiation.

Cultured and noncultured human solid tumors were analyzed for expression of Ia-like antigens with the use of two monoclonal antibodies and a rabbit antiserum against human Ia-like antigens. Of 27 tumor cells tested, 3 melanomas bound antibodies [e.g., 21,563 cpm 131I-labeled staphylococcal protein A ([131I]SpA) with monoclonal antibody Q5/6], but 24 others (1 melanoma, 9 neuroblastomas, 1 medulloblastoma, 3 gliomas, 4 sarcomas, 2 colon carcinomas, 2 transitional cell carcinomas of the bladder, 1 teratoma, and 1 squamous cell carcinoma of the lung) did so minimally or not at all (0-427 cpm [131I]SpA with antibody Q5/6. Monoclonal antibody Q5/6 was quantitatively absorbed with homogenates of 32 noncultured tumors to determine if Ia-like antigens were expressed by neoplastic cells in vivo. Ten milligrams (wet wt) each of 5 of 7 noncultured melanomas removed more than 83% (median, 85%) of the antibody. In contrast, 10 mg each of 10 neuroblastomas, 7 carcinomas, 4 sarcomas, and 4 Wilms' tumors removed less than 47% (median, 19%) of the antibody; even 100 mg of these tumors removed less than 68% (median, 44%) of the antibody.

Immunophenotypic features of human sarcomatous Wilms' tumor (SWT) were studied using a newly established mouse monoclonal antibody (5H10, IgG1). 5H10 was produced against CR-SW2, one of several transplanted SWT lines in nude mice, and defines a 200-kDa cell surface protein. The antibody was found to react equally with all subtypes of SWT; clear cell sarcoma of the kidney, malignant rhabdoid tumor of the kidney, and unclassified sarcoma. Furthermore, it reacted equivalently with surgically resected tumors, transplanted tumors in nude mice, and cell lines in vitro. On the other hand, 5H10 was entirely negative for any of the components of nephroblastic Wilms' tumor (NBW). Considering these results, 5H10 appears to recognize the antigen expressed preferentially on SWT, and therefore the subtypes of SWT may be closely related to one another immunophenotypically. In normal human tissues, however, 5H10 only reacted with fetal kidneys, its reactivity being restricted to the lower limbs of S-bodies in both the metanephros and mesonephros. No reactivity was identified in any other tissues including adult kidney. These results indicate that 5H10 detects an oncofetal antigen expressed preferentially in both SWTs and fetal kidney and that the histogenesis of SWT should be considered in connection with nephrogenesis.

Wilms' tumor, renal cell carcinoma, and neuroblastoma in animals were transplanted from donors to recipients with strong histocompatibility differences. No strong evidence of the privileged site theory was found in this study and no obvious evidence of an immunosuppressive effect of testosterone was found. The most important factor noted in these studies was that the take of tumor transplant seems to be related more to the type of tumor itself. Further studies of transplant results of such different types of tumors are warranted and are being conducted. An interaction between the hormonal supportive concept and the privileged site seems tenable.

A comparative evaluation of radioimmunoassay (RIA), indirect immunofluorescence, fluorescent antibody to membrane antigen, competitive inhibition RIA, and complement fixation methods for determining the immune status to varicella-zoster virus (VZV) showed that RIA was the most sensitive test. However, this test is still not regarded as being entirely satisfactory and possible reasons are discussed. To date, 28 children, mainly with solid tumours, have been inoculated with the Oka-strain live varicella vaccine. Two of these vaccinees developed minor reactions, but only 62% developed a RIA-detectable humoral response. Approximately 46% of the responders had lost induced antibody within 12 months of vaccination. None of the 6 vaccinees that have subsequently been in contact with varicella developed any illness suggesting that they had been protected.

HLA antigen distribution was determined in thirty patients with Wilms' tumour, and their frequencies compared with those of an ethnically matched control population. No statistically significant association was found between any single HLA antigen and Wilms' tumour disease. The value of prospective HLA typing studies, with special respect to genetic aspects, histopathological subgrouping and survival rate of Wilm's tumour patients is discussed.

The distribution in renal tumours of 3-fucosyl-N-acetyl lactosamine has been studied by using the monoclonal antibodies AGF 4.36 and AGF 4.48 and immunoperoxidase methods on tissue sections. Seven of 19 nephroblastomas and 12 of 30 renal cell carcinomas contained the epitope. In nephroblastomas the epitope was found on the terminals of type B tubules in six cases and in one case on the type A or neoplastic tubules. In renal carcinoma the antigen was found on the surface of tumour cells. The results suggest that in kidneys bearing nephroblastomas ureteric bud elements may grow into the tumour from the adjacent kidney.

An antigen was detected in pooled human nephroblastomas using antiserum prepared in rabbits against an ethylemediaminetetra acetic acid (EDTA) extract of the tumors. This antigen was not found in normal human plasma or kidney extracts, and was not related to the ABO or Forssman blood groups. The antigen was detected in extracts of cultured nephroblastoma cells, but was not present in extracts of normal human fetal kidney cell cultures. The antigen is believed to be present at the cell surface, as cell viability was not significantly lowered during the extraction procedure. A reaction of complete identity was demonstrated by Ouchterlony double diffusion experiments with this antigen and purified bovine fetuin. The antigen was not found in extracts of human fetal spleen, thymus or kidney, nor in human fetal serum. Furthermore, the antigen does not possess determinants in common with the human alpha-fetoprotein of hepatomas, nor was it detected in human renal clear cell carcinoma. Initial characterization of the antigen showed it to be nondialysable, not sedimentable at 100,000 times g for 2 h, stable to repeated freeze-thawing and to incubation at 56 degrees C for 1 h, and water soluble over a wide pH range. The antigen was susceptible to digestion with pronase and trypsin and possibly hyaluronidase, but not to ribonuclease or neuraminidase. The protein portion is therefore of major importance to the structural integrity of this antigen. The relationship between this antigen and other abnormal materials reported previously in nephroblastoma patients is being studied.

Monoclonal antibodies (mAb) for rapid diagnosis and detection of invasive bacteria and identification of pathogenic factors in infectious disease are equally important in medical microbiology and clinical pathology and may even provide a breakthrough in basic medical and cell biology research. Such a situation evolved from the application of a unique mAb against the poorly immunogenic homopolymers of alpha 2,8-linked sialic acid of Escherichia coli K1 and meningococci group B capsules which could be derived from immune-hyperreactive NZB-autoimmune mice. The cross-reactivity of this mAb with identical polysialic acid (polySA) units of the neural cell adhesion molecule (N-CAM) revealed antigenic mimicry as the basis for the escape of the above-mentioned bacteria from host immune response and immune defense. The mAb proved to be a specific and sensitive diagnostic reagent as well as a very efficient therapeutic agent in experimental E. coli K1 and meningococcal group B infections in mice. Furthermore, the mAb was found to react exclusively with long-chain polySA units characteristic of the embryonic form of N-CAM. This led to the discovery that the embryonic form of N-CAM is present outside neural tissue in the mesodermally derived kidney where it is specifically expressed during embryonic organ differentiation and reexpressed under conditions of malignant growth in nephroblastoma. Therefore, the embryonic form of N-CAM represents an onco-differentiation antigen in kidney.

Four individual tissue proteins were studied both in normal and tumoral tissue of kidney (hypernephroma, Wilms tumor) using immunochemical analysis. Occurrence of an antigen, which was absent in definitive tissue of homologous origin, as well as a decrease in biosynthesis of some homologous antigens were found in malignant tissue.

Stage-specific embryonic antigen-1 (SSEA-1) was localized on paraffin embedded, formalin fixed specimens of human renal tumors by immunoperoxidase staining using a monoclonal antibody. Of 19 renal cell carcinoma (RCC) samples tested, 12 were positive for SSEA-1; SSEA-1 was also found on distinct elements in two samples of Wilms' tumor. No correlation was found between expression of SSEA-1, and RCC morphology or pattern of growth. Because SSEA-1 is found on proximal tubules in the normal kidney, these results support the hypothesis that RCC arises from the cells of the proximal tubule. Furthermore, since greater than 60% of the RCCs examined expressed SSEA-1, this antigen may prove to be a useful target for immunolocation or therapy of metastatic RCC.

A case of a nephroblastoma harbouring numerous endocrine cells is reported. Endocrine cells were immuno-characterized as serotonin and somatostatin cells. In addition, a small group of pigmented cells, probably melanin-containing, was observed. This tumor could belong to the teratoid variety of nephroblastoma.

The Wilms' tumour is a solid childhood tumour of the kidney, consisting of blastema, tubules and mesenchyme. Embryonic tumours, such as Wilms', may arise as a result of a developmental disturbance in differentiation. The expression of class I and II major histocompatibility complex (MHC) antigens was investigated on 6 Wilms' tumours and related to that in the developing human kidney in this immunohistological study, using a panel of monoclonal antibodies. The Wilms' tumour blastemal cells were class I MHC antigen negative, but differentiated structures were positive. Class II MHC antigens were not observed in Wilms' tumours. In the developing human kidney class I MHC antigen expression was observed on glomeruli from 8 weeks and on tubules from 13 weeks gestational age. Class II MHC antigen expression was observed on glomeruli from 11 weeks and on tubules from 13 weeks gestation. These results suggest that the blastemal cells within the Wilms' tumour may reflect an early stage of development with respect to the expression of MHC antigens.

In a total of 35 children affected with malignant sufferings (except leucaemias) the haematological-immunological parameters of children surviving for a short time are compared with those surviving for a long time. Compared with children surviving for a short time those surviving for long time had a more "normal" finding initially and during the control examination made after more than 5 years of a survival time which was free of complaints and recidives. The immunologically intact condition of the organism is assumed to be decisive for this course of disease.

The presence of neonatal (cord) lymphokine-activated killer (LAK) cell activity toward natural killer cell resistant Raji and Daudi cell lines has recently been reported from our laboratory. We investigated the future therapeutic use of LAK adoptive immunotherapy by examining LAK in vitro cytotoxicity from both neonatal and adult mononuclear cells against solid tumor cell lines of relevance to pediatric oncology: SH-SY5Y (neuroblastoma), SK-NM-C (neuroblastoma-neuroepithelioma), NEP-1 (Wilms' tumor), SK-ES-1 (Ewing's sarcoma), and A-204 (rhabdomyosarcoma). Cord and adult mononuclear cells were activated by recombinant IL-2 (100 mu/ml) for 5-7 days and added in an effector:target ratio of 40:1 to 51Cr-labeled target cells. Specific cell lysis was determined after a 4-h incubation. There was a significantly high level of cord and adult LAK cytotoxicity against Wilms' (76.4 +/- 9.8 versus 77.3 +/- 6.8%) and Ewing's (84.2 +/- 5.5 versus 71.1 +/- 6.5%) cell lines and significant but moderate LAK activity against neuroepithelioma (52.0 +/- 6.6 versus 55.4 +/- 4.5%) and rhabdomyosarcoma (46.6 +/- 5.7 versus 43.9 +/- 5.2%) cell lines. There was no difference between cord and adult LAK activity toward these targets. However, a differential response toward the more classical neuroblastoma cell line, SH-SY5Y, was noted with significantly more LAK cytotoxicity from cord mononuclear cells than adult mononuclear cells (51.2 +/- 6.9 versus 28.5 +/- 8.2%) (p less than or equal to 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Of 31 patients with solid, malignant tumours, 15 were shown to have over 0.5 mg/100 ml Serum concentration of alpha-2 pregnancy-associated glycoprotein (alpha2-PAG). These increased values were found for patients with neuroblastomas, Wilms tumours and rhabdomyosarcomas. However, for several different lymphomas and haemoblastoses, alpha2-PAG could not be demonstrated with the electroimmunodiffusion technique used (Laurell). From 230 children with non-neoplastic diseases, 62 had demonstrable concentrations of alpha2-PAG, of 38 healthy children, 2 were positive, while from 50 newborn infants, with different illnesses no increased values were found. Post-operative controls using repeated determination of d2-PAG are complicated by the slow change in concentration, and by the influence of chemotherapy. The determination of alpha2-PAG for the initial diagnosis of malignant diseases in childhood and for post-operative monitoring of the disease, is therefore of only limited value at least until further investigations have been carried out.

Peripheral blood lymphocytes were studied in 22 pediatric patients suffering nephroblastoma and neuroblastoma. Monoclonal antibodies were used. Failure of T-cell immunity was registered in both groups. Nephroblastoma patients revealed high levels of natural killer cells. Immunity was studied versus clinical stage, duration of disease and response. Immunocorrection modalities are discussed.

In 45 patients with Wilms' tumor of the kidney the IgG, IgA, and IgM serum immunoglobulin levels were quantitated and 23 antigens of HLA-A and HLA-B locues were typed on the same patients' lymphocytes. In 22 individuals with increased IgA immunoglobulin level a more frequent incidence of HLA-A 1 antigen was found. This antigen was established in 62.5% of patients with IgA levels higher than 200 IU/ml. Considering the fact that 86.35% of the patients survive two years, and 16 of 22 patients (= 72.72%) are practically cured, it is suggested that the simultaneous occurrence of increased levels of IgA immunoglobulin and of HLA antigen A 1, is a favourable prognostic sign.

A hyaluronidase-sensitive component of human peritoneal fluid from a patient with Wilms' tumor when injected into rabbits has been shown to suppress the formation of humoral precipitating antibodies to certain major classes of proteins present in the fluid. Furthermore, it has been found that hyaluronic acid, when included with certain test antigens (serum albumin, fetuin) or antigen mixtures (tumor isolates or mixtures of albumin, immunoglobulin G and immunoglobulin M), produces a marked distortion or complete blockage of immunoelectrophoresis precipitin arcs, as well as altered gel chromatography elution profiles. These findings that hyaluronic acid can interfere profoundly with both the elicitation of a complete antibody response and the formation of "normal" patterns of antigen-antibody precipitates in laboratory tests supports the possibility that this polysaccharide may play an immuno-regulatory role by masking potential immunogens. Consideration of the mechanisms for these in vivo and in vitro effects suggests that there may be some common basis in an "excluded volume" property of the hyaluronate, but this does not appear sufficient to explain the complexity and selectivity of the observed phenomena.

Several monoclonal antibodies against human leukocyte differentiation antigens have been shown to react with normal kidney. Four monoclonal antibodies with different patterns of reactivity on normal kidney were tested against 20 renal epithelial neoplasms and 5 Wilms' tumors. In general, the expression of these antigens on renal tumors was faithful to their presence on normal kidney; this finding suggested that most renal tumors may be derived from proximal tubule epithelium. There was, however, both intertumor and intratumor heterogeneity of expression of these antigens, but the different phenotypes encountered did not correlate in any simple way with histologic subclassification. In contrast, the five Wilms' tumors were phenotypically different from the epithelial neoplasms, consistent with an origin from a more primitive renal cell.

A procedure for ethylenediaminetetraacetate extraction of minced Wilm's tumor was assessed as a method for isolating Wilm's tumor antigens. An antigen was detected by immunodiffusion using an adsorbed antiserum to this extract. This antigen was also found in ethylenediaminetetraacetate extracts of in vitro cultures of nephroblastoma cells.

Previous investigations on polysialic acid of the neural cell adhesion molecule NCAM in human kidney have demonstrated its presence during nephrogenesis in embryonic kidney, absence in normal adult kidney, and reexpression in Wilms' tumor. These data showed that polysialic acid of NCAM is an onco-developmental antigen in human kidney and provided more direct evidence for the metanephric origin of Wilms' tumor. In the present study, five cases of Wilms' tumor associated with nephroblastomatosis complexes were immunohistochemically investigated with a monoclonal antibody for the presence of polysialic acid. Regardless of the type of nephroblastomatosis complex, ie, renal nodular blastema, simple tubular metanephric hamartoma, sclerosing metanephric hamartoma with adenoma, or incipient Wilms' tumor, immunoreactivity for polysialic acid was found in the blastemal cells, but was undetectable in all other structural elements. Because only blastemal cells exhibited a characteristic feature of embryonal differentiating metanephric derivatives, it appears that Wilms' tumor has its origin not exclusively in nodular renal blastema but rather in blastemal cells present in the various forms of nephroblastomatosis complex. The presence of polysialic acid of NCAM in blastemal cells in such lesions indicates that further events in addition to the expression of the embryonic form of this cell adhesion molecule may be involved in the pathogenesis of Wilms' tumor.

Using a rabbit antiserum to a synthetic undecapeptide deduced from a cloned human retroviral gag-gene-related DNA sequence, we found a specific immunohistochemical reaction in all of 42 tested renal cell adenocarcinomas (RCC), while none of 17 similarly tested Wilms' tumors and 65 carcinomas at other sites were positive. The RCC included two cases that presented with distant metastases. It had not been possible to establish the origin of these until immunohistochemical staining revealed this typical reaction. Subsequent renal angiography disclosed the primary. In immunoblotting the antiserum detected an Mr 75,000 protein in RCC tissue, and this reaction was blocked by the undecapeptide. The usefulness of this protein as a tumor marker for RCC is discussed.