lewis-x-antigen and Kidney-Neoplasms

To explore the role of CD15 expression in the prognosis of clear cell renal cell carcinoma (ccRCC) in Chinese patients.. The study included 301 patients who had undergone surgery for localized ccRCC. All paraffin-embedded tumor sections were collected to make a set of tissue microarrays. CD15 expression was assessed by immunohistochemistry. The relationship between CD15 expression and survival parameters, clinicopathology features was assessed. Kaplan-Meier and Cox proportional hazards model were utilized to determine the correlation between CD15 expression and overall survival (OS).. The median follow-up time was 54.6 months (range, 3-121 months). The positive rate of CD15 expression was 81.7% (246/301). The cut-off value of CD15 expression was defined as the maximum for Youden index by plotting the receiver operating characteristic curve for survival status. As the threshold was 0.5, all cases were divided into two groups: positive expression group and negative expression group. In correlation analysis, loss of CD15 expression was correlated with female gender, higher Fuhrman nuclear grade, with sarcomatoid differentiation, with necrosis, and with vascular invasion. Kaplan-Meier analysis indicated that the OS time of patients with loss of CD15 expression was shorter than that of patients with positive CD15 expression (P = 0.013).. CD15 is a significant prognostic factor in clear cell renal cell carcinoma.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Asian People; Carcinoma, Renal Cell; Child; Child, Preschool; Female; Humans; Immunohistochemistry; Kaplan-Meier Estimate; Kidney Neoplasms; Lewis X Antigen; Male; Middle Aged; Multivariate Analysis; Prognosis; Young Adult

Changes in expression patterns of the sialyl Lewis antigens and MUC1 mucin can be considered as markers for the diagnosis of various cancers. However, there are no reports which have been devoted to analysis of differences in the sialyl Lewis antigens and MUC1 expression patterns as potential discrimination markers among different areas of clear cell renal cell carcinoma (ccRCC). The aim of this study was to determine the level of MUC1 and specific Lewis antigens on glycoproteins in three different areas: tumor (cancer tissue), intermediate zone (adjacent to tumor tissue) and normal renal cortex/medulla (uninvolved by tumor).. Study was performed on renal tissues taken from 30 patients with clear cell renal cell carcinoma. Relative amounts of sugar structures bound with proteins were determined by ELISA-like test with biotinylated lectins or monoclonal antibodies: anti-MUC1 and anti-sialyl Lewis(a/x). The study presented here provides novel information about relationship between MUC1 and sialyl Lewis antigens in the tumor, intermediate zone and noninvolved areas of normal renal tissue distant of tumor.. We have found statistically significant increase of MUC1 and sialic acid linked by α-2,3 bond with galactose in cancer tissue and in intermediate zone comparing to normal renal tissue distant of tumor. Moreover, we observed statistically significant increase of sialic acid linked by α-2,6 bond with Gal/GalNAc and sialyl Lewis(a/x) antigens in cancer tissues only, comparing to normal ones.. MUC1 and sialylated antigens can be involved in renal tumor development and can be considered as potential markers distinguishing normal renal tissue from intermediate zone and from cancer renal cells during ccRCC development.

Topics: Aged; Biomarkers, Tumor; Carcinoma, Renal Cell; Female; Humans; Kidney; Kidney Neoplasms; Lewis X Antigen; Male; Middle Aged; Mucin-1; Sialyl Lewis X Antigen

Certain carbohydrate-based biomarkers are known to correlate with cancer formation and progression. By targeting sialyl Lewis X, we have developed the first boronolectin-MS tag conjugate, which allows for MALDI-based imaging of cancer based on its cell surface carbohydrate.

Topics: Boron Compounds; Carcinoma, Renal Cell; Gene Expression Regulation, Neoplastic; Kidney Neoplasms; Lewis X Antigen; Molecular Imaging; Monosaccharides; Sialyl Lewis X Antigen; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization

To examine expression profiles of LewisX(Le(x))-related antigens, which have a possible role in hematogenous metastatic spread in various malignancies, in renal cell cancer (RCC) tissue in order to evaluate their prognostic value for patients with low-stage RCC.. Fifty-two patients with pT1-2N0M0 disease were evaluated for their expression patterns of Le(x)-related antigens using FH6 and CSLEX1 antibodies for sLe(x) and AG223 for 6-sulfo Le(x), immunohistochemically.. None of the expression levels of Le(x)-related antigens directed by the three antibodies related to the clinical outcomes of patients with low-stage RCC. However, combined use of FH6 and CSLEX1 antibodies enabled prognostic prediction, namely that patients with low intensity with FH6 and high intensity with CSLEX1 had a higher chance of disease progression and poor survival.. Expression levels Le(x)-related antigens determined by combined use of FH6 and CSLEX1 antibodies could be of value as a prognostic indicator for patients with low-stage RCC.

Topics: Antibodies, Monoclonal; Biomarkers, Tumor; Carcinoma, Renal Cell; Female; Humans; Immunoenzyme Techniques; Kidney Neoplasms; Lewis X Antigen; Male; Middle Aged; Neoplasm Staging; Oligosaccharides; Prognosis; Sialyl Lewis X Antigen

Mucinous tubular and spindle cell carcinoma is a rare and newly described type of renal cell carcinoma (RCC) with a relatively indolent behavior. However, its histogenetic origin or line of differentiation remains unclear. Twelve cases of mucinous tubular and spindle cell carcinoma were identified and retrieved from the files of 3 institutions. Detailed morphological features, as well as their immunohistochemical profile established with markers of proximal renal tubules (RCC marker antigen, CD15, and alpha-methylacyl-CoA racemase) and of distal renal tubules (kidney-specific cadherin and cytokeratin 7), were studied. The age range of the patients was 35 to 73 years with a median of 56 years. The male to female ratio was 1:3. All of the patients were alive with follow-up between 4 and 38 months. All the tumors were confined to the kidney with a mean tumor size of 6.9 cm (range, 1.8-17 cm). The tumors were composed of variable proportions of tubular and spindle cell areas with focal to prominent mucinous or myxoid stroma. Foamy macrophages were seen in 10 cases and were prominent in 4 cases. A focal compressed tubulopapillary growth pattern was seen in 10 cases. The tumor cells were uniformly cuboidal with ovoid to round nuclei and inconspicuous nucleoli (Furhman nuclear grade 3 in 6 cases). Focal necrosis was seen in 3 cases. Immunostains showed that tumors were positive for RCC marker antigen (11/12), alpha-methylacyl-CoA racemase (11/12), CD15 (8/12), CD10 (2/12), kidney-specific cadherin (1/12), and cytokeratin 7 (11/12). Its morphological features as well as a strong preferential expression of proximal tubule markers suggest that this tumor is a type of RCC with proximal tubular differentiation, which appears closely related to or represents a morphological variant of papillary RCC.

Topics: Adenocarcinoma; Adenocarcinoma, Mucinous; Adult; Aged; Antigens, Neoplasm; Biomarkers, Tumor; Cadherins; Carcinoma; Carcinoma, Papillary; Carcinoma, Renal Cell; Female; Humans; Keratin-7; Kidney Neoplasms; Lewis X Antigen; Male; Middle Aged; Mitogen-Activated Protein Kinases; Necrosis; Neprilysin; Racemases and Epimerases

We report a rare tumor called low-grade renal collecting duct carcinoma. Grossly, the tumor consisted of multiple cysts and solid white nodules, measuring 10 cm in diameter and occupying most of the renal parenchyma. Histologically, the tumor was characterized by well-differentiated tubules lined by eosinophilic cells without papillary projections, abundant predominantly extracellular mucin, minimal cellular atypia, no desmoplasia, and rare mitoses. This tumor occurs in collecting ducts and the tumor cells were positive for epithelial membrane antigen, high-molecular-weight keratin, CD15, and mitochondrial antibody and negative for CD10. Few cells stained weakly positive for ulex europaeus. Ultrastructural study showed a large number of mitochondria according to the eosinophilic cells seen in light microscopy.

Topics: Aged; Autoantibodies; Biomarkers, Tumor; Carcinoma, Renal Cell; Humans; Immunohistochemistry; Kidney Neoplasms; Kidney Tubules, Collecting; Lewis X Antigen; Male; Microvilli; Mitochondria; Mucin-1

To investigate the clinical significance of nm23-H1 gene product in sarcomatous cancer cells, because this is known as a tumor-metastasis suppressor. Renal cell carcinoma with sarcomatoid cancer cells is characterized by high malignant potential and a poor prognosis.. We investigated the expression of nm23-H1 gene product in the carcinomatous and sarcomatous component (CC and SC) of renal cell carcinoma using immunohistochemical techniques and the relationships between the expression and clinicopathologic features. We also examined the expression of matrix metalloproteinase (MMP)-2, MMP-9, sialyl Lewis X, and c-erbB-2 in the SC because these proteins are regulated by the nm23-H1 gene or its products.. We examined 20 renal cell carcinoma specimens that contained an SC and CC. The CC of 12 of the 20 tumors stained positively for nm23-H1 gene product. In contrast, the SC of only 3 of the 20 stained positive. The reduced expression of nm23-H1 gene product in the SC correlated significantly with tumor invasion (P <0.01), but not with tumor size or metastasis. In contrast, the expression of the nm23-H1 gene product in the CC was not associated with these pathologic features. Expression of the nm23-H1 gene product correlated negatively with MMP-2 expression (r = -0.48, P = 0.03). Other factors did not show such significant correlations with nm23-H1 gene product expression.. Our results suggest that low expression of nm23-H1 gene products may play important roles in tumor invasion, and that this process is mediated in part by overexpression of MMP-2.

Topics: Aged; Antigens, Neoplasm; Carcinoma, Renal Cell; Female; Gene Expression; Humans; Kidney Neoplasms; Lewis X Antigen; Male; Matrix Metalloproteinase 2; Matrix Metalloproteinase 9; Middle Aged; Neoplasm Invasiveness; NM23 Nucleoside Diphosphate Kinases; Nucleoside-Diphosphate Kinase; Oligosaccharides; Receptor, ErbB-2; Sarcoma; Sialyl Lewis X Antigen

Carbohydrate antigens and E-selectin play important roles in the invasion and metastasis of cancers. We examined the expression of these antigens and their ligand protein, E-selectin, in urothelial carcinomas to evaluate whether their staining is correlated with the grade and stage of cancer. We studied the expression of carbohydrate antigens (type 1 and type 2 blood-group antigens) and E-selectin in urothelial carcinomas of the renal pelvis, ureter, and urinary bladder in 52 patients by staining SSEA-1 (LeX), sialyl LeX (sLeX), DU-PAN-2, CA19-9, and E-selectin with 5 different monoclonal antibodies (MAbs) to evaluate whether their staining correlated with cancer grade and stage. The differences between organs with regard to the degree of expression of these antigens were not evident. Type 2 antigens (SSEA-1 and sialyl LeX) are frequently expressed in the tumor cells regardless of atypical grade. The expression level of type 1 antigens (DU-PAN-2 and CA19-9) is lower than that of type 2 antigens. However, the presence of DU-PAN-2 tends to correlate with the grade of atypia; however, that of CA19-9 is inversely proportional to the grade of atypia. The lack of CA19-9 and appearance of DU-PAN-2 in urothelial carcinoma implies a high malignant potential. The expression of E-selectin can be correlated with stage and grade of tumor atypia. Type 2 antigen and E-selectin may be involved in tumor invasion and metastasis.

Topics: Aged; Aged, 80 and over; Antigens, Neoplasm; Biomarkers, Tumor; CA-19-9 Antigen; E-Selectin; Female; Humans; Immunohistochemistry; Kidney Neoplasms; Lewis X Antigen; Male; Middle Aged; Oligosaccharides; Sialyl Lewis X Antigen; Ureteral Neoplasms; Urinary Bladder Neoplasms; Urologic Neoplasms; Urothelium

Immunoperoxidase analysis was performed to evaluate the phenotypic expression of eight renal differentiation antigens in five nephroblastomas, one clear cell sarcoma of the kidney (CCSK), one rhabdoid tumor of the kidney (RTK), and four related tumors. A total of 19 fetal and pediatric kidneys, including two 6th-week mesonephric tissues, were comparatively studied. All the specimens were fixed in formalin and embedded in paraffin. Neural cell adhesion molecule (NCAM), a marker of the nephrogenic zone of the developing kidney, was consistently expressed in the epithelial and blastematous components of nephroblastomas of the common type. The epithelial components also commonly expressed NK1 and Leu 7 (CD57), and the findings may reflect that both were positive in immature proximal tubules directly differentiating from the NCAM-positive immature fetal tubuloglomerular buds. In two cases, the epithelial component was immunoreactive for CD10 and WT1 gene product (WT1-GP). Leu M1, epithelial membrane antigen and CA15-3 were only focally expressed in nephroblastomas. Rhabdomyoblasts in the stroma were positive for WT1-GP. CCSK was featured by the expression of NCAM and CD10. In RTK, focal epithelial differentiation was discerned, with focal positivity of WT1-GP and negativity of NCAM. In congenital mesoblastic nephroma, the stromal spindle cells were strongly immunoreactive for WT1-GP, while WT1-GP was not expressed in solitary multilocular cyst of the kidney. Pancortical nephroblastomatosis was featured by the diffuse subcapsular reappearance of immature metanephric tissue. Nephroblastomas and related conditions thus offer an adequate model for studying human nephrogenesis.

Topics: Adolescent; Adult; Antigens, Surface; CD57 Antigens; Child; Child, Preschool; DNA-Binding Proteins; Female; Humans; Immunohistochemistry; Infant; Infant, Newborn; Kidney; Kidney Neoplasms; Killer Cells, Natural; Lewis X Antigen; Male; Mucin-1; Neprilysin; Neural Cell Adhesion Molecules; Neuroblastoma; Sarcoma, Clear Cell; Transcription Factors; WT1 Proteins

Although rare, renal cell carcinoma (RCC) can metastasize to the bladder. When this occurs, it might complicate diagnosis. Morphologically, RCC can be confused with transitional cell carcinomas (TCCs), especially those exhibiting clear cell features, and also with other bladder tumors, such as paragangliomas and metastatic melanomas. We report seven cases of RCC metastatic to the bladder that occurred in 6 men and 1 woman who were 35 to 69 years old. The most common presenting symptom was the reappearance of hematuria, which developed from 2 to 131 months (mean, 41.3 mo) after the removal of the primary RCC. In all of the patients, the metastatic RCC involved multiple organs; no case had an isolated metastasis to the bladder. The prognosis was poor, and five patients died of disease between 4 and 24 months (mean, 12.8 mo) after diagnosis of the metastasis to the bladder. The remaining two patients were lost to follow-up. All of the tumors were conventional clear or "granular" cell RCCs, with nuclear grades of 2 or 3. In five patients, metastases were confined to the lamina propria, but in two patients, tumors involved the muscularis propria as well. A comparative immunohistochemical study showed that metastatic RCCs were positive for CAM5.2, vimentin, and Leu-M1, and negative for cytokeratin 20, cytokeratin 7, 34betaE12, carcinoembryonic antigen, S-100 protein, HMB45, and chromogranin. Classic and clear cell TCCs were positive for all of the cytokeratins and carcinoembryonic antigen and negative for vimentin. Paragangliomas were positive for chromogranin and showed scattered positivity for the S-100 protein in the sustentacular cells. Metastatic melanomas were positive for S-100 protein and HMB45. The histologic appearance of RCC, particularly the delicate fibrovascular stroma with abundant sinusoidal vessels, is a feature that can be used to recognize the tumor. When there is difficulty diagnosing metastatic RCC, TCC, or other tumors in the bladder, the immunohistochemical findings can assist in the differential diagnosis.

Topics: Adult; Aged; Antigens, Neoplasm; Carcinoembryonic Antigen; Carcinoma, Renal Cell; Carcinoma, Transitional Cell; Chromogranins; Diagnosis, Differential; Female; Humans; Immunohistochemistry; Intermediate Filament Proteins; Keratin-20; Keratin-7; Keratins; Kidney Neoplasms; Lewis X Antigen; Male; Melanoma; Melanoma-Specific Antigens; Middle Aged; Neoplasm Proteins; Paraganglioma; S100 Proteins; Urinary Bladder Neoplasms; Vimentin

Renal cell carcinoma (RCC) arising in acquired cystic kidney disease (ACKD) is considered to be a tumor of low malignant potential, compared with classic RCC. The aim of the present study was to identify any significant differences in the antigenic profiles or tumor cell proliferative activity of ACKD-associated RCC and classic RCC that might be responsible for differences in their biologic behavior. We studied the immunohistochemical profiles and proliferative activity of 12 classic RCCs and 5 ACKD-associated RCCs with markers of proximal tubules (Leu M1, alpha-1 antitrypsin, CAM 5.2), markers of distal tubules (Arachis hypogaea lectin, AE1/AE3, epithelial membrane antigen [EMAJ, CAM 5.2), vimentin, and proliferating cell nuclear antigen (PCNA). We performed proliferation analysis with the CAS 200 image analysis system. For each case, 8 to 20 fields of tumor tissue in the areas of maximal PCNA staining were quantitated, and the percentage of PCNA-positive nuclear area for each individual tumor was calculated. All of the five ACKD-associated RCCs expressed AE1/AE3, EMA, and CAM 5.2 in more than 50% of the tumor cells. Arachis hypogaea lectin was significantly expressed in three of the five ACKD-associated RCCs. Leu M1 and alpha-1 antitrypsin reacted with fewer than 10% of the tumor cells in all of the five ACKD-associated RCCs. In contrast, the 12 classic RCCs showed expression of CAM 5.2 in 11 cases, alpha-1 antitrypsin in 10 cases, Leu M1 in 9, EMA in 8, and AE1/AE3 in 3 cases in more than 50% of the tumor cells and a totally negative reaction with Arachis hypogaea lectin in 8 cases, EMA in 4, AE1/AE3 in 4, and vimentin in 5 cases. Although coexpression of proximal and distal tubule markers was seen in some cases of RCC in either category, there was uniform and strong staining for distal tubule markers in ACKD-associated RCC and for proximal tubule markers in classic RCC. The mean percentage of PCNA-positive nuclear area for the ACKD-associated RCCs (2.41%) was significantly (P < .05) less than that of the classic RCCs (21.42%). The differences in expression of proximal and distal tubule markers and proliferative activity might be responsible for the differences in the biologic behavior of ACKD-associated RCC and classic RCC.

Topics: Adult; Aged; Aged, 80 and over; alpha 1-Antitrypsin; Analysis of Variance; Biomarkers, Tumor; Carcinoma, Renal Cell; Cell Nucleus; Cell Transformation, Neoplastic; Female; Humans; Image Processing, Computer-Assisted; Immunohistochemistry; Keratins; Kidney Diseases, Cystic; Kidney Neoplasms; Kidney Tubules; Lewis X Antigen; Male; Middle Aged; Mucin-1; Peanut Agglutinin; Proliferating Cell Nuclear Antigen; Vimentin

The most common clinical form of lung cancer is a disseminated disease with distant metastases; several years of cancer progression precede presentation, and this ultimately limits the efficacy of curative therapy. In this immunohistochemical study, we examined a mucinous adenocarcinoma cell line, maintained by xenogeneic transplantation, and a spontaneous metastatic variant which produces distant tumors (in liver, spleen and kidney). The aim was to investigate possible parameters which characterize the metastatic process. Histopathological comparison between the two subcutaneous transplanted tumor lines showed that both lines presented a similar cellular morphology, a different pattern of cellular growth and an increased vascularization in the metastatic line with respect to its parent. All the tumor sections expressed differential immune reactivity with monoclonal antibodies against Lewis y (MAb C14), sialyl-Lewis x (MAb SNH3) and Lewis x (MAb FH2) determinants. Neither expressed MUC 1 mucins detectable with monoclonal antibodies reactive with the mucin protein core (MAbs C595 and SM3) nor was carcinoembryonic antigen (MAb C365) expressed. Neoplastic cells were reactive with an anti-pan cytokeratin monoclonal antibody confirming their epithelial histogenesis. Our findings have been evaluated with respect to defining metastatic phenotypes in lung cancer by examination of distinct histopathological and immunological parameters.

Topics: Adenocarcinoma, Mucinous; Animals; Antibodies, Monoclonal; Apoptosis; Biomarkers, Tumor; Carcinoembryonic Antigen; Cell Nucleus; Cytoplasm; Gangliosides; Humans; Image Processing, Computer-Assisted; Immunoenzyme Techniques; Injections, Subcutaneous; Kidney Neoplasms; Lewis Blood Group Antigens; Lewis X Antigen; Liver Neoplasms, Experimental; Lung Neoplasms; Mice; Mice, Nude; Mucin-1; Mucins; Neoplasm Proteins; Neoplasm Transplantation; Neoplastic Stem Cells; Oligopeptides; Peptide Fragments; Phenotype; Sialyl Lewis X Antigen; Splenic Neoplasms; Transplantation, Heterologous; Tumor Cells, Cultured

(BACKGROUND). E-selectin is an adhesion molecule expressed on IL-1 activated endothelial cells and it binds to carbohydrate ligands such as sialy Lewis A antigen (SLeA) or Lewis X antigen (SLeX) on cancer cells. This mechanism is supposed to play an important role during hematogenous metastasis. Some of renal cell carcinomas (RCC) are known to produce inflammatory cytokines such as IL-1 beta and IL-6 and clinical evidence shows that the prognosis of this type of tumor is generally poor. We investigated whether this adhesion molecule was involved in hematogenous metastasis. (METHOD). In the present study, soluble E-selectin level was measured in the sera of 89 patients with RCC prior to nephrectomy or IFN treatment using sanwich ELISA method. (RESULTS). The results indicated that high E-selectin concentration in the patients' sera was correlated with low incidence of metastasis and consequently correlated with good prognosis of RCC patients. Inflammatory serum parameters, such as serum C reactive protein (CRP), immunosuppressive acid protein (IAP) and erythrocyte sediment rate (ESR) were also assessed and these parameters were revealed to be negatively correlated with the serum level of E-selectin. In order to investigate this mechanism, we performed in vitro study on RCC cell/endothelial cell adhesion. IL-1 beta enhanced adhesion of 2 RCC cell lines and this adhesion was partially inhibited by adding exogenous E-selectin into the culture medium. Expression of SLeA and SLeX were demonstrated on the cell surface of 2 RCC cell lines by flowcytometric analysis. (CONCLUSION). The results suggested that E-selectin and SLeX/SLeA interaction was involved in the adhesion between RCC and endothelial cells and also inflammatory cytokine production by RCC cells was a risk factor for metastasis through E-selectin induction. Although expression of E-selectin on endothelial cells facilitates metastasis, excessive production of E-selectin into the serum was suggested to have inhibitory effect against metastasis.

Topics: Aged; Carcinoma, Renal Cell; E-Selectin; Female; Humans; Kidney Neoplasms; Lewis X Antigen; Male; Middle Aged; Neoplasm Metastasis; Prognosis; Tumor Cells, Cultured

Monoclonal antibodies were used to study the expression of three recently characterized basement membrane components and two carbohydrate antigens in 11 renal-cell carcinomas, using immunohistological and biochemical techniques. The expression of several site-specific kidney antigens in renal-cell carcinoma were studied to determine the origin of the carcinoma and if it is possible further classify this type of carcinoma. Tubulointerstitial nephritis antigen (TIN) and two alpha-chains of type IV collagen, alpha 1 (IV) and alpha 3 (IV) were studied. In addition the expression of carbohydrate antigens Lex and SLex, which also exhibit site-specific distribution were characterized. Lex and SLex antibodies stained the majority of the tumours. TIN was expressed in 9 of 11 tumours, the alpha 1 (IV) chain was present in all 11, and the alpha 3 (IV) chain in two of the 11 tumours. Interestingly, the two alpha 3 (IV)-positive tumours were the same two that were negative for TIN. In normal tissue alpha 3 (IV) is found in distal tubules while TIN is found in proximal tubules. Our results are consistent with earlier observations that the proximal tubule is the origin of most renal-cell carcinomas, but the results also indicate that renal-cell carcinoma may originate from the distal tubule.

Topics: Antibodies, Monoclonal; Antigens, Surface; Carcinoma, Renal Cell; Cell Adhesion Molecules; Collagen; Humans; Immunohistochemistry; Kidney Neoplasms; Kidney Tubules, Distal; Kidney Tubules, Proximal; Lewis X Antigen; Membrane Glycoproteins; Oligosaccharides; Sialyl Lewis X Antigen; Telomere-Binding Proteins

Metastatic renal cell carcinoma has occasionally been reported to mimic malignant pleural mesothelioma. Morphologically, histochemically and immunohistochemically, similarities in the two tumours exist making their differentiation difficult, particularly in biopsy specimens. The aim of this study was to make a comparative immunohistochemical analysis of the two tumours by use of a panel of four antibodies (Leu M1; Ber EP4; thrombomodulin and Tamm-Horsfall protein). Their suitability in differentiating between the two tumours was assessed. We examined 20 cases of renal cell carcinoma and 20 cases of malignant pleural mesothelioma. On immunostaining with Leu M1, 14 of 20 renal cell carcinomas were positive, yielding 70% sensitivity and 95% specificity and one of 20 mesothelioma. In comparison, Ber EP4 antibody stained only seven of 20 of the renal cell carcinomas. In addition, it was noted that four tubulo-papillary pattern renal cell carcinomas stained positively with both anti-Leu M1 antibody and Ber EP4 antibody. Thrombomodulin immunostaining was present in 11 of 20 mesotheliomas (55% sensitivity and demonstrated 95% specificity) and one of 20 renal cell carcinomas. For epithelial mesotheliomas only, thrombomodulin staining was identified in 10 of 14 cases. In the differentiation of renal cell carcinoma from epithelial mesothelioma we recommend the use of Leu M1 and thrombomodulin as diagnostically useful markers. None of the antibodies used in this study was effective in distinguishing sarcomatoid renal cell carcinoma from sarcomatous mesothelioma. Tamm-Horsfall protein showed little diagnostic utility in differentiating the two tumours.

Topics: Antibodies, Monoclonal; Antigens, Neoplasm; Carcinoma, Renal Cell; Diagnosis, Differential; Humans; Kidney Neoplasms; Lewis X Antigen; Mesothelioma; Mucoproteins; Pleural Neoplasms; Thrombomodulin; Uromodulin

Chromophobe renal cell carcinoma (RCC) is a recently established subtype of RCC, which has rarely been reported in Japan. In this communication, the authors report two Japanese cases of chromophobe RCC together with the immunohistochemical findings. The tumors were composed of sheets and cribriform glands formed by tumor cells with cloudy and reticular cytoplasm. Ultrastructurally, the cytoplasm was filled with numerous microvesicles. The tumor cells were positive for cytokeratin, epithelial membrane antigen, and Tamm-Horsfall protein. Occasionally, LeuM1-positive cells were also noted. Vimentin was negative, unlike the usual RCC. Reactivity for peanut agglutinin was more frequent than that to Lotus tetragonolobus agglutinin. The results of this study suggest that the tumor cells possessed phenotypes similar to the distal nephron rather than to the proximal tubular cells.

Topics: Adult; Aged; Antigens, CD; Antigens, Differentiation, Myelomonocytic; Carcinoma, Renal Cell; Female; Humans; Immunohistochemistry; Keratins; Kidney Neoplasms; Lectins; Lewis X Antigen; Vimentin

Apoptosis (programmed cell death) is a basic physiological process which determines specific patterns of tissue size and shape, and balance of cell number, during morphogenesis, and seems to play an integral role in oncogenic progression. Since dramatic changes of cellular glycosylation pattern are well known to be closely correlated with differentiation, development and oncogenesis, it is likely that similar specific changes are associated with apoptosis. However, this possibility has not been systematically investigated. We therefore carried out histological studies of many tumours and normal tissues for which a high incidence of apoptosis is believed to occur. Sections were stained with monoclonal antibodies (MoAbs) directed to carbohydrate antigens Le(y) and Le(x), proliferating cellular nuclear antigen (PCNA) and Fas (previously claimed to be an apoptosis-inducing antigen). Antibody staining patterns were compared with morphological cell characteristics as revealed by haematoxylin/eosin staining, and DNA fragmentation patterns (a marker of apoptosis) as revealed by 3'-OH nick-end labelling technique. We found that expression of Le(y) (defined by MoAb BM1) is closely correlated with the process of apoptosis, but not with cell proliferation or necrosis. Within Le(y)-positive areas of tissue sections, typical apoptotic morphological changes and DNA fragmentation (as revealed by positive nick-end labelling) were frequently observed in certain loci, although not all Le(y)-positive cells showed such signs of apoptosis. Le(y)-positive areas showed consistent negative staining by MoAb directed to PCNA and negative or weak staining by MoAb directed to Fas antigen, regardless of tissue source. No such trends were observed for Le(x) glycosylation. We conclude that Le(y) expression is a useful phenotypic marker predictive of apoptosis, i.e. some (although not all) Le(y)-positive cells subsequently become apoptotic.

Topics: Antibodies, Monoclonal; Apoptosis; Carbohydrate Sequence; Carcinoma, Squamous Cell; Cell Division; Esophageal Neoplasms; Humans; Immunohistochemistry; Kidney Neoplasms; Lewis X Antigen; Molecular Sequence Data; Mucous Membrane; Necrosis; Nephrons; Stomach Neoplasms

Renal cell carcinomas are immunohistochemically positive for oligosaccharides with the Le(x) determinant (Gal beta 1----4[Fuc alpha 1----3]GlcNAc) and its derivatives, as oncofetal antigens, and their expression is closely related to a better prognosis of the patients. This study was designed to clarify the difference in antigen localization at the ultrastructural level between renal cell carcinoma and normal tissues. In normal kidneys, Le(x) detected by monoclonal antibody (MAb) FH 2 and sialylated extended Le(x) (sialyl Le(x)-i) by MAb FH 6 were identified along the plasma membrane of microvilli of proximal tubule epithelial cells, with occasional immunoreactivity along the basolateral plasma membranes. Intracellular localization was very sparse. Renal cell carcinoma showed localization of Le(x) and sialyl Le(x)-i antigens along the cell membrane and in the cytosol as aggregates or filaments. Immunoreactive materials were also observed in the lumen formed among carcinoma cells. The cytosolic immunoreactivity, not observed in the normal kidney, was regarded as "abnormal cytosolic accumulation" of the antigens. This pattern was more pronounced in clear-cell carcinoma. Pretreatment of specimens with chloroform-methanol, which extracts glycolipids, decreased immunoreactivity in carcinoma tissues, particularly that in the cytosol. The extracts contained substances immunoreactive for MAb FH6. Our study has demonstrated that (a) remarkable changes occur in the ultrastructural localization patterns of sialyl Le(x)-i and Le(x) in renal cell carcinoma and (b) considerable amounts of glycolipids are contained in the substances with sialyl Le(x)-i deposited in the cytosol of clear-cell carcinoma.

Topics: Adenocarcinoma; Antibodies, Monoclonal; Antigens, Tumor-Associated, Carbohydrate; Cell Membrane; Chloroform; Cryopreservation; Female; Glycolipids; Humans; Immunohistochemistry; Kidney; Kidney Neoplasms; Lewis X Antigen; Male; Methanol; Microscopy, Immunoelectron; Middle Aged

We performed immunohistochemical examination of serial sections of human fetal and adult renal tissue as well as human renal carcinoma tissue, using monoclonal antibodies T5A7, 1B2, FH2, FH4, and FH6. These monoclonal antibodies were directed to lacto series type 2 antigens with sugar-chain structures: lactosylceramide, lactoneotetraosylceramide (paragloboside), Lex (a chemically well-defined fucosyl carbohydrate antigen), difucosyl Lex, and sialosyl-difucosyl Lex, respectively. The staining pattern in fetal renal tissue changed significantly according to the stage of organogenesis. In addition, expression of the antigens, especially paragloboside and sialosyl-difucosyl Lex, was closely related to the prognosis of the patient. These results suggest that the expression of a series of oncofetal antigens in development or differentiation of organs is reflected in the reversion to an immature pattern of antigenic expression in tumor tissue. The pattern of antigen expression in renal tumors offers a good criterion for ascertaining the degree of tumor differentiation and malignancy and is valuable for determining prognosis.

Topics: Adult; Antibodies, Monoclonal; Antigens, CD; Antigens, Neoplasm; Carcinoma, Renal Cell; Embryo, Mammalian; Female; Fetus; Globosides; Glycolipids; Glycosphingolipids; Humans; Immunohistochemistry; Kidney; Kidney Neoplasms; Lactosylceramides; Lewis X Antigen; Neoplasm Staging; Pregnancy; Prognosis

Topics: Antigens, Neoplasm; Carcinoma, Renal Cell; Glycolipids; Humans; Immunohistochemistry; Kidney Neoplasms; Lewis X Antigen; Prognosis

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.

Topics: Antigens, Neoplasm; Antigens, Surface; Carcinoma, Renal Cell; Frozen Sections; Glycolipids; Histocytochemistry; Humans; Immunoenzyme Techniques; Kidney Neoplasms; Lewis X Antigen; Paraffin; Wilms Tumor

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.

Topics: Antibodies, Monoclonal; Antigens, Neoplasm; Carcinoma; Humans; Kidney Neoplasms; Kidney Tubules, Collecting; Lewis X Antigen; Sarcoma; Wilms Tumor

Distribution patterns of specific fucose-containing antigens having X determinant (Gal beta 1----4[Fuc alpha 1----3]GlcNAc) as well as the di- or trimeric X determinants (Gal beta 1----4[Fuc alpha 1----3]GlcNAc beta 1----3Gal beta 1----4[Fuc alpha 1----3]-GlcNAc) in the developing human embryo and fetus and in human cancer have been examined using immunohistological techniques. Tissue sections were stained with monoclonal antibody FH3, which defines X determinant, and with monoclonal antibody FH4, which defines di- or trimeric X determinant. The following general trends in the expression of the antigens defined by FH3 and FH4 have been observed: (a) A well-organized, orderly appearance and disappearance of the antigens was observed during the histogenesis of various epithelia of gastrointestinal and other organs. The developmental stage exhibiting the maximum antigen expression is different for each organ. (b) The X determinant defined by FH3 was expressed approximately 2 wk earlier than the di- or trimeric X determinant defined by FH4, and the antigen defined by FH4 regressed more rapidly and more completely than the X determinant defined by FH3 on further development of epithelial tissue. Thus, expression of the FH4 antigen is highly limited to specific types of cells in newborn and adult epithelial tissues. (c) The antigen defined by FH4 was strongly expressed in the majority of tubular and papillary adenocarcinoma of stomach, adenocarcinoma of colon, and infiltrating ductal carcinoma of breast and its metastatic lesions. No antigen was found in poorly differentiated stomach adenocarcinoma, squamous lung carcinoma, and many other types of tumors from ovary, testis, prostate, skin, and muscle. The presence of the antigen defined by FH4 is therefore limited to carcinoma of the stomach, colon, and breast and can be regarded as a retrograde expression of the antigen to a certain stage of fetal development in which expression of this antigen was maximal.

Topics: Adult; Antibodies, Monoclonal; Antigens, Neoplasm; Breast Neoplasms; Bronchi; Cerebrosides; Colonic Neoplasms; Digestive System; Embryo, Mammalian; Female; Fetus; Glycolipids; Histocytochemistry; Humans; Infant, Newborn; Kidney Neoplasms; Lewis X Antigen; Pregnancy; Stomach Neoplasms