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Query: UMLS:C0027627 (metastases)
 103,950 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

HLA class I and II expression was studied on 244 (177 primary and 67 metastatic) solid human tumours of different origin. Alkaline immunophosphatase (APAAP) and immunoperoxidase were used on cryostatic sections to stain MHC antigens. Monomorphic MoAbs were used against class I heavy chain, beta 2-microglobulin, DR, DQ and DP molecules. Class I expression was homogeneous on colon, melanoma and epidermoidal primitive tumours. Loss of HLA class I antigens was more frequent on basal cell carcinomas and sarcomas and was related to tumour differentiation on larynx carcinoma. Class I expression was heterogeneous on breast, larynx and stomach primitive neoplasias. Class I negative tumours were more frequent on metastatic than on primitive melanomas. Divergence of class I between primary tumours and autologous metastases was observed on melanomas, larynx and colorectal carcinomas. Class II expression was heterogeneous on all tumours and in a large number of cases was associated with high intensity of leukocytic infiltrate. HLA-DR expression was higher than HLA-DP and HLA-DQ (DR greater than DP greater than DQ) and was related to tumour progression. Four human tumour cell lines were modulated with recombinant interferon-gamma for HLA class I and II antigens. Different HLA profiles were obtained: increased class I and II expression, increased class II or a low response. Finally, class I genes from 22 tumours were compared with autologous normal cells by Southern blot analysis: 12 tumours were class I positive and 10 negative. No clear differences in RFLP were observed that could be associated with class I rearrangement. The results are discussed in relation to the role that histocompatibility antigens may play in tumour progression and invasiveness.
Clin Exp Metastasis
PMID:Phenotypic expression of histocompatibility antigens in human primary tumours and metastases. 249 52

The expression of HLA class I and II antigens was analysed in 30 primary gastric carcinomas, 27 autologous lymph node metastases and 25 autologous gastric mucosae. We used an immune alkaline phosphatase technique on cryostatic sections and mAbs directed against HLA class I monomorphic determinants, HLA-B locus-specific products and HLA-DR, -DP and -DQ molecules. In addition HLA class I genes were analysed in tumour tissue and compared by Southern blots with the RFLP from autologous mucosa using locus-specific HLA probes. Finally the infiltrating mononuclear cells were studied on gastric tumours and adjacent mucosa with mAbs defining CD4, CD8 and CD11b differentiation antigens. The results obtained showed that three out of 27 primary gastric carcinomas completely lack HLA-ABC antigens (10%). In addition, two primary tumours presented a variable expression. The remaining 22 tumours presented a homogeneous positive HLA class I expression. Interestingly, when the autologous mucosa was analysed, only 12 out 25 specimens were homogeneously stained with mAbs against HLA class I antigens, suggesting that this tissue may lack the expression of HLA antigens before becoming malignant. Indeed, the majority of the gastric carcinomas studied presented a higher HLA-ABC antigenic expression than autologous mucosa. Finally, the HLA expression observed in the primary tumour was similar to that observed in autologous metastases. As a second part of the study we have found a direct relationship between the expression of HLA-DR antigens in mucosa and the intensity of inflammatory infiltration. This relationship was not maintained in the tumour tissue. In the mucosa the CD4-positive T cell was the predominant lymphocyte, while it was CD8 in the HLA-DR-positive tumours. Finally the RFLP of class I genes did not show any differences in any of the cases when compared with autologous mucosa. We included in these studies DNAs from HLA class I-negative tumours, HLA positive and HLA-B-negative ones.
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PMID:MHC class I and II antigens on gastric carcinomas and autologous mucosa. 263 12

A series of 38 primary laryngeal and hypopharyngeal tumours, 15 lymph-node metastases and normal tissue were evaluated in frozen sections for the expression of MHC class I and II antigens, using monomorphic monoclonal antibodies (MAbs) to HLA-ABC, beta 2-microglobulin, DR, DP, DQ, HLA-B and polymorphic HLA-ABC antigens. Normal distant mucosa of larynx reacted to anti-class I antibodies but not to anti-class II. In 9 primary tumours (23.7%) HLA class I antigens were not observed. The remaining 29 showed a strong reaction to not observed. The remaining 29 showed a strong reaction to anti-HLA-ABC (heavy chain) and anti-beta 2-microglobulin, although in 3 cases out of 29 no staining was observed with anti-HLA-B locus-specific MAbs. These selective losses were confirmed using the corresponding anti-HLA polymorphic MAbs. For HLA class II molecules, only DR was observed in 3 of 38 cases. Defective HLA class I expression statistically correlates with high scores according to Jakobsson's criteria for histopathological tumour grading. Loss of HLA-ABC antigens was most frequent among the cases with poor differentiation (6/8 cases). On the contrary, class II antigen expression was correlated with a well differentiated pattern and a more favourable prognosis (p less than 0.001). We have found differences in HLA class I expression when comparing primary tumours and autologous metastases (3/9 cases). Immunoprecipitation and SDS-PAGE of class I antigens, Northern and Southern blot analyses of MHC class I genes were performed. We have not detected class I gene rearrangement using HLA coding and locus-specific non-coding probes. However, we have found a class I transcription defect that corresponds with a class-I-negative phenotype.
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PMID:Histocompatibility antigens in primary and metastatic squamous cell carcinoma of the larynx. 264 39

The expression of HLA class I antigens was studied in 99 primary tumour (colorectal, gastric and laryngeal carcinomas) and 57 autologous metastases using immunohistological techniques and monoclonal antibodies against class I monomorphic determinants, HLA-B isotypic determinants and HLA polymorphic determinants. Fourteen per cent of colorectal, 9.6% of gastric and 20% of laryngeal carcinomas completely lacked class I molecules. Selective losses of HLA-B antigens were also detected in 8.8, 3.4 and 5.8% of these tumours respectively. Taking into account complete and selective loss of HLA-B the average alteration in the class I molecules expression totalled 21%. The comparison of class I expression between primary tumours and autologous metastases showed differences in 24% of the patients. These differences consisted mainly in a decrease of class I expression by metastases. Nevertheless, four types of divergence were detected in laryngeal carcinomas, namely: +/-, +/+, -/+, -/-. In addition, a clear correlation between degree of differentiation and class I expression was observed in laryngeal tumours. Finally, when class I gene RFLPs were compared with DNA from 15 tumours and autologous normal mucosa or peripheral lymphocytes, no differences were detected between these samples.
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PMID:HLA class I gene expression on human primary tumours and autologous metastases: demonstration of selective losses of HLA antigens on colorectal, gastric and laryngeal carcinomas. 264 29

Tissue samples and cell cultures from Wilms' tumour matched histologically normal kidney samples and EBV transformed B cells from the same patients, were analysed to detect changes in the structure and expression of the N-myc oncogene. The levels of expression of HLA class I and hypoxanthine guanine phosphoribosyl transferase were also measured in the various RNA preparations. Related tissue samples, from sources including congenital mesoblastic nephroma, paediatric neuroblastoma and a number of foetal tissues were also tested. Northern blot analysis indicated that the levels of N-myc were higher in Wilms' tumour tissues (with no parallel increase in gene copy number) compared to all other sources of material including foetal kidney. Particularly high levels of expression were observed in a number of the Wilms' tumours, several of which produced metastases. In situ hybridization, using [35S]-labelled RNA probes, confirmed that the high levels of N-myc RNA were present in the blastemal elements in the Wilms' tumour. All the tissue cultures, and tissue samples from other sources, except foetal brain and neuroblastoma, contained uniformly low levels of N-myc RNA.
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PMID:Expression of the N-myc oncogene in Wilms' tumour and related tissues. 284 12

Class I and HLA-DR antigen expression were studied with histochemical techniques involving monomorphic monoclonal antibodies in 49 cases of human malignant melanomas, 20 primary and 29 metastatic. A large percentage (90%) of primary melanomas were positive for HLA class I, while those primary lesions showing lowest levels of class I antigen expression were at the upper end of the range of invasiveness and possessed a higher metastatic potential. Expression of HLA-DR molecules on primary melanomas was low (25% of all cases) and HLA-DR-positive melanomas were among the most aggressive. In metastatic melanomas, HLA class I expression was less common than in primary lesions. The lowest percentage of cases positive for HLA class I was found for cutaneous metastases. HLA-DR molecules were more frequently expressed by lymph node metastases than on primary melanomas. The comparison of the expression of HLA class I and HLA-DR molecules by primary melanomas and their autologous metastases revealed a high degree of heterogeneity. Class I genes were further studied by Southern blot assays. No differences were found in restriction fragments for class I genes among 4 melanomas and their autologous lymphocytes, 2 of which were positive and 2 negative for class I expression.
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PMID:Phenotypic and genetic analysis of HLA class I and HLA-DR antigen expression on human melanomas. 307 72

Human melanoma cells freshly isolated from 20 patients with primary and 73 patients with metastatic melanomas were analyzed by indirect immunofluorescence staining with monoclonal antibodies (MoAb) to class I (HLA-A, -B, and -C) and class II (HLA-DR and -DQ) antigens and to melanoma associated antigen (MAA). The latter included the GD3-MAA and the high molecular weight MAA. HLA class I antigens were present in 91 and 93% of primary and metastatic tumors, respectively. GD3-MAA was detected in 100% of primary and 80% of metastatic tumors. Whereas the high molecular weight MAA was expressed in 75% of tumors. Sixty % of primary and 50% of metastatic melanomas were stained by anti-HLA-DR MoAb, whereas 38 and 21% of cases, respectively, were stained by anti-HLA-DQ MoAb. Marked phenotypic heterogeneity was evident among primary and metastatic tumors, including different metastases from the same patient. Moreover, in vitro culture of melanoma cells isolated from metastases was associated with an increase from 50 to 75% of tumors stained by anti-HLA-DR MoAb but not of tumors positive for HLA class I antigens and MAA. In vitro incubation with partially purified or recombinant human gamma-interferon enhanced the expression of HLA-DR antigens on all short-term cultured melanoma cells tested but induced and/or augmented the expression of HLA-DQ antigens only in 5 of the 8 cases examined. The average increase in antigenic expression was higher for HLA-DQ than for HLA-DR antigens. Flow cytometric measurement of DNA content of melanoma cells treated with gamma-interferon revealed that the increase of HLA-DR and -DQ expression induced by gamma-interferon was independent from the cell cycle of the tumor cells.
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PMID:Classes I and II HLA and melanoma-associated antigen expression and modulation on melanoma cells isolated from primary and metastatic lesions. 307 89

Indirect immunofluorescence staining with monoclonal antibodies has shown a differential distribution of HLA-DR, DQ, and DP antigens in normal tissues of nonlymphoid origin. The distribution of HLA-DP antigens is similar to that of HLA-DR antigens, while that of HLA-DQ antigens is more restricted. Malignant transformation of cells of nonlymphoid origin may be associated with the appearance of the gene products of the HLA-D region. HLA-DR antigens appear more frequently than the other two types of HLA class II antigens and HLA-DP antigens more frequently than HLA-DQ antigens. Differential expression of the gene products of the HLA-D region was also found in autologous metastases removed from different anatomic sites from patients with melanoma. The HLA class II phenotype of surgically removed malignant lesions did not correlate with the degree of differentiation of tumor cells and/or with the expression and/or cellular distribution of HLA class I antigens. Furthermore, in melanoma lesions, no relationship was found between the HLA class II phenotype and the expression of 3 membrane bound and 1 cytoplasmic melanoma associated antigen recognized by monoclonal antibodies. The functional significance and the practical implications of the differential expression of the gene products of the HLA-D region by tumor cells are discussed.
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PMID:Gene products of the HLA-D region in normal and malignant tissues of nonlymphoid origin. 308 70

The work described here demonstrates the importance of major histocompatibility complex class I antigens for the control of tumor growth and metastasis by the host's immune system. In certain murine tumor cells which have lost expression of H-2 class I antigens, a de novo expression of H-2 can be achieved by transfection with syngeneic class I genes. In contrast to the parental cells the transfected tumors do not grow any more in syngeneic mice, or in other cases they do not form metastases. The studies suggest that the de novo expression of the H-2 antigens renders the tumors highly immunogenic and leads to effective recognition of a tumor-associated antigen in conjunction with the transfected H-2 antigen. These conclusions were confirmed in other tumor systems. For example, separation of a heterogeneous tumor into clones expressing high or low amounts of H-2 showed that only the tumor cell with low H-2 grew well in syngeneic mice, whereas the H-2 high tumor clones were rejected. In other studies in vitro induction by IFN-gamma of H-2 antigen on H-2 negative tumors led to reduced tumor growth in vivo which was due to the increased immunogenicity. About 10% of human tumors are also low or defective for HLA class I expression and often these tumors appear to be more malignant. The class I negative tumors could either have arisen from class I low or negative tissues or are HLA loss variants which escaped the attack of the immune system. Altogether, our studies and the data of other laboratories demonstrate the important role of class I antigens for anti-tumor immunity and they suggest that modulation of class I expression by gene transfection or by induction with soluble mediators could be a useful tool for the manipulation of tumor immunity.
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PMID:The influence of major histocompatibility complex class I antigens on tumor growth and metastasis. 331 98

Malignant transformation of melanocytes and further neoplastic progression may be associated with qualitative and/or quantitative changes in expression of HLA class I and class II antigens. Since previous immunohistochemical studies of surgically removed melanoma lesions have suggested a relationship in the expression of HLA class I and class II antigens, we have investigated the expression of these antigens at the single cell level. Double immunofluorescence staining of frozen sections of melanoma metastases and immunoelectron microscopic double labelling of melanoma cell suspensions prepared from three of these lesions has detected three HLA phenotypes on the large majority of melanoma cells: either both HLA class I and class II antigens, neither HLA antigen or only HLA class I antigens. In four out of the 11 lesions a few melanoma cells were found to express HLA class II antigens and to lack HLA class I antigens. A relationship was also found in the level of expression of HLA class I and class II antigens, as estimated by the intensity of staining with monoclonal antibodies. The level of expression of HLA class II antigens appeared to be similar to or lower than that of HLA class I antigens on the large majority of melanoma cells. This coordinated heterogeneity in the expression of HLA class I and class II antigens by melanoma cells may have implications in the interactions of tumour cells with the host's immune system.
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PMID:Associated expression of HLA class I and class II antigens on melanoma cells in surgically removed metastases. 353 48


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