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K C Gatter

Publications and source records attributed to K C Gatter.

At least 127 records · Page 7Linked to original sources
PubMed1995

Detection of NPM-ALK DNA rearrangement in CD30 positive anaplastic large cell lymphoma.

CD30 positive anaplastic large cell lymphoma (ALCL) is a type of non-Hodgkin's lymphoma associated with a specific chromosome translocation between chromosomes 2 and 5. Recent molecular characterization of the translocation breakpoint has identified a gene fusion between NPM (nucleophosmin) and ALK (anaplastic lymphoma kinase). Using a DNA hybridization technique, the NPM rearrangement was found among 5/5 ALCL samples. We have developed a PCT methodology which has enabled the detection of the NPM-ALK rearrangements amongst seven t(2;5)(p23;q35) ALCL cases based on a long-range PCR of genomic DNA. The rapidity and robustness of this method may have diagnostic applications for ALCL.

Anaplastic Lymphoma Kinase↗
PubMed1995

Mutations in the p53 gene are not limited to classic 'hot spots' and are not predictive of p53 protein expression in high-grade non-Hodgkin's lymphoma.

We have investigated the relationship between the p53 genotype and phenotype in a series of 22 high-grade non-Hodgkin's lymphomas (NHLs) in which we sequenced the p53 gene open reading frame (exons 2-11). Immunostaining for p53 was already available for these cases. Mutations were found in 10/22 cases (45%) and 3/10 were in exons 4 or 10 outside the classic 'hot spot' regions (exons 5-8). Comparison with immunostaining indicated that, besides cases with the 'expected' patterns (in which gene mutation and protein detection were either both present or both absent) there were also cases in which p53 protein was detected in the absence of any mutation and those with a mutant gene in which the protein was undetectable. These data show that: (1) in high-grade NHLs mutations frequently occur outside the classic hot spot regions and (2) staining for p53 is not predictive of the status of the gene, i.e. whether or not a mutation is present. Therefore in order to document p53 involvement in lymphoid tumours it is necessary both to sequence at least the whole translated open reading frame of the gene and to show evidence of protein expression by immunostaining.

Amino Acid Sequence↗
PubMed1995

Heterogeneity of bcl-2 expression in MALT lymphoma.

Bcl-2 protein expression was studied in a series of 58 MALT lymphomas using a monoclonal antibody which recognises this protein in routinely processed paraffin embedded tissue. Thirty-three of 58 cases showed heterogeneity for bcl-2 expression, 18 of 58 cases were bcl-2 positive and 7 of 58 were bcl-2 negative. High grade and low grade MALT lymphomas showed different patterns of staining. All 21 low grade tumours were positive for bcl-2, though in seven cases only a proportion of the neoplastic cells expressed this protein. In the 37 high grade tumours the majority of the neoplastic cells were negative with seven cases showing no reactivity at all. These findings give further support to the theory that MALT lymphomas differ in pathogenesis to nodal lymphomas and suggest that the good prognosis of MALT lymphomas may partly be explained by the fact that they maintain a normal pattern of bcl-2 expression.

Gastrointestinal Neoplasms↗
PubMed1995

Accumulation of wild-type p53 in meningiomas.

The p53 tumour suppressor gene contributes to the regulation of DNA repair and the initiation of apoptosis. Mutations of this gene and nuclear accumulation of its protein product are features of a large variety of tumours. A histological spectrum of meningiomas, including anaplastic examples and a meningosarcoma, was analysed for accumulation of the p53 protein and mutations in exons 4-9 of the p53 gene. No mutations were found, but 9/34 (26%) tumours showed accumulation of the p53 protein. The p53-positive meningiomas came from across the histological spectrum and were not restricted to the anaplastic group. The accumulation of wild-type p53 in a proportion of meningiomas may reflect this gene's role in DNA repair, or its enhanced stability when bound to cellular proteins such as the mdm-2 gene product.

Antibodies, Monoclonal↗
PubMed1995

Apoptosis in cerebral astrocytic tumours and its relationship to expression of the bcl-2 and p53 proteins.

Apoptosis is an important determinant of tumour growth which can be regulated by the bcl-2 and p53 genes. This study examines the relationship between apoptosis, growth fraction (Ki-67 immunolabelling index), and accumulation of the bcl-2 and p53 proteins in a spectrum of cerebral astrocytic tumours (n = 81), including fibrillary astrocytomas (n = 16), anaplastic astrocytomas (n = 19), and glioblastomas (n = 46). Median apoptosis indices (AIs) increased across this spectrum of tumours, and a significant (P < 0.0001) correlation was demonstrated between AI and Ki-67 labelling index (LI). Immunolabelling with the bcl-2 antibody was found in 44% of fibrillary astrocytomas, 42% of anaplastic astrocytomas, and 28% of glioblastomas. It was also found in the vascular endothelial proliferation typically seen in glioblastomas, and in the giant, multinucleated cells of some glioblastomas. No clear relationship between AI and bcl-2 accumulation was evident. Immunolabelling with the p53 antibody was found in 56% of fibrillary astrocytomas, 79% of anaplastic astrocytomas, and 50% of glioblastomas. No clear relationship between AI and patterns of p53 immunolabelling was evident. Equal proportions of p53-positive tumours were bcl-2 positive and bcl-2 negative, but a small proportion of p53-negative tumours was bcl-2 positive. The correlation between AI and Ki-67 LI is in line with findings in other malignant tumours. We suggest that the regulation of apoptosis in astrocytic tumours is too complex for a clear association between AI and bcl-2 and p53 protein expression to be demonstrated.

Antibodies, Monoclonal↗
PubMed1995

Immunohistochemical detection of p53 and Bcl-2 proteins in Hashimoto's thyroiditis and primary thyroid lymphomas.

AIMS: To investigate whether immunohistochemical staining using p53 and/or bcl-2 distinguishes between florid Hashimoto's thyroiditis and low grade mucosa associated lymphoid tissue (MALT) lymphoma of the thyroid. METHODS: Ten cases of Hashimoto's thyroiditis and eight of primary thyroid lymphoma were stained with monoclonal antibodies directed against p53 and bcl-2. RESULTS: In Hashimoto's thyroiditis most small lymphoid cells in mantle zones, within the thyroid parenchyma and in lymphoepithelial lesions expressed bcl-2 protein. Very occasional centroblasts in reactive germinal centres were positive for p53, but all other lymphoid cells from cases of Hashimoto's disease were negative for p53. In diffuse, low grade lymphomas bcl-2 protein was uniformly expressed by most tumour cells. However, low grade lymphomas with a follicular pattern did not express bcl-2. The diffuse, low grade lymphomas were negative for p53, while occasional larger cells in the follicular subtype were positive. Both high grade lymphomas were bcl-2 negative but strongly p53 positive. CONCLUSIONS: This study indicates that there is an inverse correlation between p53 and bcl-2 immunostaining in thyroid lymphomas (low grade lymphomas: bcl-2 positive, p53 negative; high grade lymphomas: bcl-2 negative, p53 positive). Furthermore, immunohistochemical staining for bcl-2 and p53 proteins does not distinguish florid Hashimoto's thyroiditis from diffuse, low grade thyroid lymphoma.

Biomarkers, Tumor↗
PubMed1995

Oncogene proteins and proliferation antigens in thymomas: increased expression of epidermal growth factor receptor and Ki67 antigen.

AIMS: To examine thymomas for proteins encoded by oncogenes and to determine whether their presence correlates with tumour growth and associated myasthenia gravis. METHODS: Sections of 24 thymomas were incubated with anti-EGF receptor (EGF-R), anti-Ki67 antigen, anti-p53, and anti-bcl-2 antibodies, and then stained using the alkaline phosphatase/anti-alkaline phosphatase (APAAP) technique. Cell suspensions and epithelial cell cultures from some of the tumours were also studied. RESULTS: Whereas EGF-R expression was not detected in any of the controls (but only in a 20 week old fetus), it was detected in neoplastic epithelial cells of all thymomas, and was most strongly expressed in metastases and in samples from donors with severe myasthenia gravis. Ki67 labelling was also increased, especially in the larger thymomas. Epithelial expression of both of these markers was confirmed in fresh cell suspensions and monolayer cultures from the five available cases. In contrast, p53 and bcl-2 were not detected in the neoplastic cells, but bcl-2 was present in the intermingling thymocytes. CONCLUSIONS: Neoplastic thymoma cells express EGF-R and Ki67, but there is no concomitant increase in the expression of p53 and bcl-2 proteins. Increased EGF-R expression may result in increased proliferation of neoplastic cells and also in myasthenia gravis. Measurement of EGF-R concentrations may be of prognostic value. The bcl-2 staining pattern in T lymphocytes illustrates the broad spectrum of maturational stages in thymoma lymphocytes.

Adolescent↗
PubMed1995

p53 Overexpression in laryngeal squamous cell carcinoma and dysplasia.

Aim-To investigate the expression of p53 protein in invasive squamous cell carcinoma (SCC) of the larynx and dysplasia in relation to histological grade and tobacco smoking.Method-Paraffin wax embedded tissue sections from 41 cases of invasive SCC of the larynx, 28 cases of dysplasia and 14 control laryngeal biopsy specimens were studied immunohistochemically using two anti-p53 monoclonal antibodies (DO7 and 1801). The Streptavidin/horseradish peroxidase method was used after microwave antigen retrieval and a semiquantitative method was applied to assess the extent of p53 expression.Results-Of the cases of invasive SCC of the larynx, 78% (32/41), regardless of histological grade, overexpressed p53 compared with only 30% (eight of 28) of cases of mild dysplasia. A gradual increase in p53 expression from mild to severe dysplasia (60%) was observed, and only three of 14 control biopsy specimens of laryngeal nodules showed occasional weakly positive basal cells.Conclusion-The gradual increase in p53 expression from mild to severe dysplasia to invasive SCC indicates that p53 overexpression is an early event in laryngeal carcinogenesis which may lead to invasive malignancy. p53 overexpression may be related to environmental factors as most of the patients smoked tobacco. Microwave postfixation may be essential for the reliable detection of p53.

Journal Article↗
PubMed1994

Normal human tissues, in addition to some tumors, express multiple different CD44 isoforms.

At least 20 different isoforms of the human CD44 lymphocyte-homing receptor/hyaluronan receptor have been described to date that arise from the differential splicing of up to 10 alternative exons (termed v1-v10) encoding the membrane-proximal extracellular domain. Although numerous analyses at the mRNA level have indicated tissue-specific expression of CD44 variants, few analyses have been performed at the protein level because of limited availability of suitable monoclonal antibodies. Recently, however, exon-specific monoclonal antibodies have been generated using bacterial fusion proteins, and these have been reported to detect high levels of vCD44 containing the v6 exon on human tumors. Together with earlier evidence linking this particular exon with tumor metastasis in the rat, these latter experiments have led to the interpretation that v6 splice variants play a causative role in tumor dissemination. In this paper we describe the use of a new and comprehensive panel of CD44 exon-specific monoclonal antibodies generated against a recombinant CD44(v3-10)-immunoglobulin chimera to study vCD44 expression in a large number of normal and neoplastic tissues. We show that the expression of vCD44 varies greatly among different human tumors and that some express either very low levels of vCD44 or no CD44 at all. Furthermore, we demonstrate that expression is not limited to isoforms containing the v6 exon but includes variants carrying v3, v4/5, and v8/9. Additionally, normal epithelial tissues are shown to express considerable levels of these same vCD44 isoforms. Such results argue against a ubiquitous role for vCD44 isoforms in promoting tumor growth and metastasis.

Antibodies, Monoclonal↗
PubMed1994

bcl-2 in normal human breast and carcinoma, association with oestrogen receptor-positive, epidermal growth factor receptor-negative tumours and in situ cancer.

The role of bcl-2 expression in solid tumours is as yet undefined. It was, therefore, the purpose of this study to investigate expression of bcl-2 protein in 111 human breast carcinomas using immunohistochemistry and the monoclonal antibody bcl-2 124. Expression was then compared with the established indicators of prognosis and biological behaviour in malignant breast disease. No relationship could be observed between bcl-2 and node status, tumour size, differentiation, type or age at excision. However, a strong positive relationship was seen between bcl-2 and oestrogen receptor (ER), with 70 of 88 (80%) bcl-2-positive tumours being ER positive also, compared with seven of 23 (30%) bcl-2-negative tumours being ER positive (P < 0.0001). The converse was found when bcl-2 was compared with epidermal growth factor receptor (EGFR). A strong negative relationship was observed, with 26 of 88 (30%) bcl-2-positive tumours being EGFR positive, compared with 16 of 23 (70%) bcl-2-negative tumours being EGFR positive (P = 0.001), raising the possibility that bcl-2 is an ER-regulated gene. An inverse relationship was also found between bcl-2 and the oncogenes c-erbB-2 and p53. Thus, loss of bcl-2 expression in breast cancer is associated with a range of molecular markers of poor prognosis and may define part of an ER-negative, EGFR-positive phenotype.

Breast↗
PubMed1994

Monoclonal antibodies that recognize the type-2 activin receptor, ACTR2.

Monoclonal antibodies (MAbs) were raised in mice against a bacterial fusion protein composed of the intracellular serine/threonine kinase domain of the type-2 activin receptor, ACTR2, fused to glutathione S-transferase. Three MAbs with high affinity toward the ACTR2 kinase domain were isolated, one of which recognized specifically ACTR2 expressed transiently in vascular endothelial cells. These reagents should be of use in the elucidation of mechanisms of transmembrane signaling by this member of the emerging receptor serine threonine kinase family.

Activin Receptors↗
PubMed1994

Distribution of the cdc2 gene product in normal tissues: an immunocytochemical study using four new monoclonal antibodies.

The reproductive cycle in eukaryotic cells is partly controlled by the p34 protein kinase, the product of the cdc2 gene. We report here the tissue reactivity of four new anti-cdc2 monoclonal antibodies in relation to the known proliferation markers Ki-67 and JC1. In tissues where proliferation occurs, germinal centres in the tonsil, basal layers of tonsular epithelium and skin, cortex of the thymus, seminiferous tubules of the testis and epithelium of the colon, the anti-cdc2 antibodies gave positive nuclear staining as did the proliferation markers. The percentage of positive cells was, however, lower with the cdc2 antibodies. Given the role of the cdc2 gene at specific points of the cell cycle, these antibodies are potentially useful as markers of different phases of the cell cycle and may help to detect abnormalities in cell cycle control in disease.

Antibodies, Monoclonal↗
PubMed1994

The expression of the B-cell marker mb-1 (CD79a) in Hodgkin's disease.

Recent evidence indicates that membrane-bound immunoglobulin on B lymphocytes is associated with a molecule which comprises the products of the mb-1 and B29 genes. This molecule is a highly specific marker for B-cells, presumably because of its central functional role in antigen triggering, and has recently been clustered as CD79a at the 5th Leucocyte Workshop. Recently there has been controversy surrounding reports of B-cell antigen expression by Reed-Sternberg and related cells, and we have therefore studied 108 cases of Hodgkin's disease immunohistochemically using a novel antibody which detects mb-1 protein in paraffin sections. The results were compared with those achieved using antibody L26 to detect CD20. The mb-1 protein was present in the neoplastic cells in all 14 cases of lymphocyte predominance Hodgkin's disease studied, and CD20 immunoreactivity was also found in seven of the eight cases of this subtype studied. Of the non-lymphocyte predominance cases, 20% (19/94) expressed mb-1 and 30% (20/67) CD20 in the Reed-Sternberg cells, but the cells positive for either of these two markers usually constituted only a very small proportion of the neoplastic population. However, in occasional cases (one of 94 for mb-1 and five of 67 for CD20), more than 50% of the neoplastic cells expressed one or both B-cell antigens. These results confirm the B-cell origin of the neoplastic cells in lymphocyte predominance Hodgkin's disease, but they also indicate that, contrary to our previous study, mb-1 expression may occasionally be found in what appears, on histological grounds, to be other types of Hodgkin's disease.

Animals↗
PubMed1994

A proposal for classification of lymphoid neoplasms (by the International Lymphoma Study Group).

A new classification of lymphoid neoplasms, mostly based on existing terminology, is proposed by the International Lymphoma Study Group. The proposed classification was reached through a consensus of the members, despite their diverse backgrounds, and consists of a listing of currently recognized clinicopathological entities. These tumours are divided into three major categories: B-cell neoplasms, T-cell and postulated natural killer cell neoplasms, and Hodgkin's disease. The characterization of each entity is based on a synthesis of all available information. This concept departs from a purely morphological approach to lymphoma classification, which is considered to be inadequate, because many biologically distinctive lymphoma types can exhibit a broad and overlapping morphological spectrum. Some entities are provisional, pending further data to confirm that their recognition is reproducible. The salient clinicopathological features of each entity are summarized in this review.

Hodgkin Disease↗
PubMed1994

Expression of aminopeptidase-n (CD 13) in normal tissues and malignant neoplasms of epithelial and lymphoid origin.

AIMS: To provide a detailed knowledge of the distribution of the CD13 molecule, also known as the protease aminopeptidase-N, on both normal tissues and malignant neoplasms of epithelial and lymphoid origin. METHODS: CD13 antigen was examined by immunocytochemistry, using a recently produced antibody (VS5E) alongside a commercially available anti-CD13 monoclonal antibody. The VS5E recognising CD13 was produced by immunising a doxorubicin resistant breast cancer cell line (MCF-7-ADr). A striking feature of this antibody was that it stained the doxorubicin resistant cells but not the parental cell line. Both antibodies were tested on a broad range of normal tissues and three common types of epithelial malignancy (colon n = 28, lung n = 30, breast n = 35), and 12 cases of Hodgkin's and 52 of non-Hodgkin's lymphomas. RESULTS: CD13 was expressed on many tissue and cell types outside the haematopoietic system. In particular it was present on breast epithelium and in 20% (seven of 35) of breast carcinomas, but absent in normal and neoplastic colonic and bronchial tissues and lymphomas. CONCLUSIONS: This study provides not only detailed information about the expression of the CD13 antigen, but also raises the important possibility that CD13 expression may correlate with drug resistance in breast carcinomas.

Antigens, CD↗
PubMed1994

Cellular distribution of human leucocyte adhesion molecule ICAM-3.

AIMS: To describe the distribution of the recently cloned human leucocyte adhesion molecule ICAM-3 in normal and neoplastic tissues and cell lines. METHODS: A panel of four monoclonal antibodies to ICAM-3 were used to stain cell lines and sections of human lymphoid tissues using the alkaline phosphatase-anti-alkaline phosphatase immunocytochemical method (APAAP). RESULTS: In peripheral blood ICAM-3 was detected on monocytes, granulocytes, and most lymphocytes. In sections of human lymphoid tissue the antigen was also found on most lymphocytes, but many of the proliferating B cells found in the germinal centres of secondary lymphoid follicles were ICAM-3 negative. ICAM-3 was also found on neoplastic white cells (in chronic lymphocytic leukaemia, hairy cell leukaemia, acute and chronic myeloid leukaemia, and multiple myeloma) with the exception of Reed-Sternberg cells in Hodgkin's disease, many of which were negative. ICAM-3 was consistently absent from cells and tissues of non-haemopoietic origin. Endothelium (which expresses ICAM-1) was negative for ICAM-3, with the exception of vessels in some neoplastic lymphoid samples which showed variable staining for ICAM-3. CONCLUSIONS: These findings suggest that ICAM-3 is essentially restricted to the haemopoietic system and is reciprocal in its expression to ICAM-1, in that it is present on resting cells and its level falls as a result of cell activation.

Antibodies, Monoclonal↗
PubMed1994

An immunohistochemical study of the pathology of fatal malaria. Evidence for widespread endothelial activation and a potential role for intercellular adhesion molecule-1 in cerebral sequestration.

The sequestration of parasitized erythrocytes in the microvasculature of vital organs is central to the pathogenesis of severe Plasmodium falciparum malaria. This process is mediated by specific interactions between parasite adherence ligands and host receptors on vascular endothelium such as intercellular adhesion molecule-1 (ICAM-1) and CD36. Using immunohistochemistry we have examined the distribution of putative sequestration receptors in different organs from fatal cases of P. falciparum malaria and noninfected controls. Receptor expression and parasite sequestration in the brain were quantified and correlated. Fatal malaria was associated with widespread induction of endothelial activation markers, with significantly higher levels of ICAM-1 and E-selectin expression on vessels in the brain. In contrast, cerebral endothelial CD36 and thrombospondin staining were sparse, with no evidence for increased expression in malaria. There was highly significant co-localization of sequestration with the expression of ICAM-1, CD36, and E-selectin in cerebral vessels but no cellular inflammatory response. These results suggest that these receptors have a role in sequestration in vivo and indicate that systemic endothelial activation is a feature of fatal malaria.

Adult↗