Showing papers by "Adrian C Bateman published in 1999"

Human leukocyte antigens and cancer: is it in our genes?

Abstract: Human leukocyte antigens (HLAs) are widely expressed cell surface molecules which present antigenic peptides to T-lymphocytes, thus modulating the immune response. The efficiency of peptide presentation by HLAs is dependent on the extreme polymorphism in the HLA-encoding loci within the major histocompatibility complex (MHC). HLA polymorphism is known to alter disease susceptibility and progression in a range of predominantly inflammatory conditions, many of which are T-lymphocyte-mediated. More recently, the importance of alterations in HLA expression and polymorphisms within HLA-encoding loci has emerged in the development of malignancy. This review concentrates on the role of HLA polymorphism in malignant disease, with discussion of the major cancers in which HLA associations have become clear, as well as the potential mechanisms by which HLA polymorphisms may act as important factors, or cofactors, in the pathogenesis of malignant disease. In addition, the role of certain non-HLA genes within the MHC in the pathogenesis of malignancy is also considered briefly.

HLA class II DRB1 and DQB1 allelic polymorphism and sclerosing lymphocytic lobulitis of the breast.

Abstract: BACKGROUND: Sclerosing lymphocytic lobulitis is an inflammatory disorder of the breast. The pattern of inflammation, expression of HLA class II DR by breast epithelium and association with autoimmune disorders, particularly insulin dependent diabetes mellitus (IDDM), together suggest an autoimmune aetiology. AIM: To test the hypothesis that susceptibility to sclerosing lymphocytic lobulitis may be linked to patient HLA class II DRB1 alleles, particularly DRB1*03 and DRB1*04, suggested by a previous small uncontrolled study. METHODS: HLA class II DRB1 and DQB1 genotypes were compared between a series of 28 sclerosing patients with lymphocytic lobulitis and 300 controls, using polymerase chain reaction (PCR) based typing of DNA extracted from formalin fixed, paraffin embedded biopsies. RESULTS: Results from the 28 patients (nine with IDDM) showed an increased frequency of DRB1*04 compared with controls (61% v 33%, p = 0.01), but no significant differences for other genotypes. In patients with IDDM, the frequencies of DRB1*04 (89%, p = 0.001) and DQB1*0302 (100% v 21%, p = 0.0001)--a genotype that is in linkage disequilibrium with DRB1*04--were increased compared with controls. However, in the patients without IDDM, the frequencies of DRB1*04 (50%) and DQB1*0302 (14%) were not significantly increased. CONCLUSIONS: The increased frequency of HLA DRB1*04 in sclerosing lymphocytic lobulitis appears to reflect its association with IDDM, a condition in which DRB1*04 is increased in frequency.

Polymerase chain reaction based human leucocyte antigen genotyping for the investigation of suspected gastrointestinal biopsy contamination

Abstract: BACKGROUND—Mislabelling or contamination of surgical specimens may lead to diagnostic inaccuracy, particularly within gastrointestinal pathology when multiple small mucosal biopsy specimens are commonly taken, and where a tiny fragment of foreign tissue may be indistinguishable from true biopsy material using histological assessment alone. AIMS—To assess the utility of polymerase chain reaction (PCR) based human leucocyte antigen (HLA) genotyping techniques for the investigation of potentially mislabelled or contaminated gastrointestinal biopsy specimens. PATIENTS—Ten cases (28 samples) in which mislabelling or contamination was suspected, comprising four upper gastrointestinal tract biopsies and six colonoscopic biopsy series. METHODS—Direct and nested PCR-sequence specific primer (SSP) based HLA class II genotyping was performed on DNA extracted from formalin fixed and paraffin wax embedded tissue (23 samples) or peripheral blood leucocytes (five samples). RESULTS—A full HLA-DRB1 genotype was determined in all 28 samples. In seven cases the HLA-DRB1 genotype of the putative contaminant was different to that of the corresponding reference tissue, confirming different individual origins for the contaminant and reference material. In one case the contaminant tissue was shown to possess the same HLA-DRB1 alleles as a second patient (probable source). In the remaining three cases the same HLA-DRB1 alleles were detected within the potential contaminant and reference tissues. CONCLUSIONS—PCR based HLA class II genotyping is a valuable tool for investigating potential contamination or mislabelling within gastrointestinal biopsy specimens and this report has confirmed contamination in seven of ten cases studied. Keywords: polymerase chain reaction; human leucocyte antigen; tissue typing; contamination; mislabelling

Calcium oxalate (Weddellite) crystals within ductal carcinoma in situ.

Abstract: L26 (CD20) is one of the most useful markers in the diagnosis of lymphoid neoplasms, but when Gala et al tested a large panel of antibodies for use in Bouin fixed bone marrow, L26 was one of the few antibodies which failed to stain. Vassallo and Pinto now suggest that if Zenker solution is used instead of Bouin solution, satisfactory L26 staining may be obtained. However, Zenker has its own technical and safety disadvantages and we note that, in contrast to the findings of Gala et al, successful immunostaining of Bouin fixed material for L26 has previously been noted and we get consistent, strong immunostaining for L26. We have fixed marrow biopsies in Bouin fluid for many years because of its excellent morphology in haematoxylin and eosin (H&E) staining and for its ease of use. (Following three to six hours of fixation in Bouin, biopsies are decalcified overnight in 10% formic acid. A short daytime processing cycle allows H&E sections to be reviewed late on the day following biopsy.) For immunohistochemistry we use antigen retrieval in antigen unmasking solution (Vector Laboratories) with pressure cooking for two minutes before applying L26 (Dako) followed by the avidin-biotin complex (ABC) technique. In addition to staining B cells, we note that L26 may give weak to moderate staining of megakaryocytes, a finding we have also seen with B5 fixed material. Nucleolar staining, described in epithelial and other cells types and regarded as non-specific, may be seen in some marrow blast cells. Figure 1 shows L26 staining of an infiltrate of hairy cell leukaemia in a Bouin fixed marrow biopsy. Gala et al indicate that there is limited information on the range of antibodies which stain in Bouin fixed marrow so we have reviewed all the immunostains on our bone marrow biopsies for the past year. In addition to the antibodies described by Gala we have found successful staining for L26, leucocyte common antibody, CD79a, CD34, CD68 (PGM1), epithelial membrane antigen, glycophorin A and C, S-100, and tryptase.