High expression of glycolytic and pigment proteins is associated with worse clinical outcome in stage III melanoma
Johan FalkeniusJoakim LundebergHemming JohanssonRainer TuominenMarianne Frostvik-StoltJohan HanssonSuzanne Egyházi Brage
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Abstract:
There are insufficient numbers of prognostic factors available for prediction of clinical outcome in patients with stage III malignant cutaneous melanoma, even when known adverse pathological risk factors, such as macrometastasis, number of lymph node metastases, and ulceration are taken into consideration. The aim of this study was therefore to identify additional prognostic factors to better predict patients with a high risk of relapse, thus enabling us to better determine the need for adjuvant treatment in stage III disease. An RNA oligonucleotide microarray study was performed on first regional lymph node metastases in 42 patients with stage III melanoma: 23 patients with short-term survival (≤ 13 months) and 19 with long-term survival (≥ 60 months), to identify genes associated with clinical outcome. Candidate genes were validated by real-time PCR and immunohistochemical analysis. Several gene ontology (GO) categories were highly significantly differentially expressed including glycolysis (GO: 0006096; P<0.001) and the pigment biosynthetic process (GO: 0046148; P<0.001), in which overexpression was associated with short-disease-specific survival. Three overexpressed glycolytic genes, GAPDHS, GAPDH, and PKM2, and two pigment-related genes, TYRP1 and OCA2, were selected for validation. A significant difference in GAPDHS protein expression between short- and long-term survivors (P=0.021) and a trend for PKM2 (P=0.093) was observed in univariate analysis. Positive expression of at least two of four proteins (GAPDHS, GAPDH, PKM2, TYRP1) in immunohistochemical analysis was found to be an independent adverse prognostic factor for disease-specific survival (P=0.011). Our results indicate that this prognostic panel in combination with established risk factors may contribute to an improved prediction of patients with a high risk of relapse.Keywords:
Univariate analysis
Abstract KCl extracts of Melanoma 14, a human melanoma cell line grown in chemically defined serum‐free medium, inhibited leukocyte migration in 19/36 (53%) patients with malignant melanoma. Only 4/23 (17%) controls with non‐melanoma malignancies and 4/28 (14%) normal subjects with no history of cancer were similarly inhibited. Only 2/27 melanoma patients tested against KCl extracts of normal muscle tissue excised from the donor of Melanoma 14 were significantly inhibited. Patients with Stage I (localized) melanoma and patients with Stage III (generalized) melanoma reacted with roughly equal frequency but the number of patients in each group was too small for meaningful statistical analysis. Leukocytes from the donor of Melanoma 14 were tested in a completely autologous system against extracts of Melanoma 14 tissue culture cells and extracts of autologous muscle and were specifically inhibited by the Melanoma 14 tissue culture extract (Migration Index = 0.67) but not by the extract of normal muscle (Migration Index = 0.96). Only 7/32 (22%) melanoma patients were significantly inhibited by an extract of non‐melanoma tumor. These results suggest that melanoma‐associated antigens are present in soluble extracts of this tumor line. Such extracts could provide a continuing source of standard melanoma‐associated antigens for purification and chemical characterization and for diagnostic and prognostic tests in patients with malignant melanoma.
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Melanoma diagnosis
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OBJECTIVES:
The aim of this study was to determine immunohistochemical expression of HIF-1α and its intensity in bioptic samples of patients with primary melanoma and patients with metastatic melanoma and to determine the localization of the expression of HIF-1α.
EXAMINEES AND METHODS:
The study was done on 20 paraffin sections of biopsy samples of patients with malignant melanoma who were threated at the Department of Oncology, University Hospital of Split. We choosed 10 patients with primary melanoma and 10 patients with metastatic melanoma whose histopathological material was taken from the archives of the Clinical Department of Pathology, Clinical Institute of Pathology, Forensic Medicine and Citology, Clinical Hospital Split.
RESULTS:
Results of this study indicate that Hif-1α was present in all samples of primary melanoma and metastatic melanoma, and that there was positive immunohistochemical expression. Intensity of immunohistochemical expression of HIF-1α in samples of primary melanoma was mild (50%) or moderate (50%), while in metastatic melanoma samples was mild (30%), moderate (50%) or stong (20%). Localisation of immunohistochemical expression of HIF-1α was same in both groups of samples (primary and metastatic melanoma samples); citoplasm (60%),and citoplasm and nucleus (40%).
CONCLUSION:
Hif-1α was present in all samples of primary melanoma and metastatic melanoma, and there was positive immunohistochemical expression. There was strong upregulation of intensity of HIF-1α expression in metastatic melanoma samples in comparison to primary melanoma samples, that suggested that HIF-1α might be an important factor for malignant melanoma growth and in the future might be predictor for regional lymph node metastasis. Also HIF-1α could be target molecule for malignant melanoma therapy.
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Immunohistochemistry has become an important tool in research and in surgical pathology. Rapid growth of a new methods in immunohistochemistry supplement traditional histochemical and histological light microscopy investigations. Immunohistochemistry has given pathologists a chance to location different antigens on the cell surface as well as in the cell compartments. The expression of antigens are mostly influenced by factors connected with tissue processing; fixation and embedding. The aim of present article is to show the role of these factors and their influence on some immunohistochemical staining results. Not all the problems are discussed here, the main goal which authors would like to obtain is to show the way how to solve problems which can occur during immunohistochemical staining procedure. They want also to delineate the importance of standardization in immunohistochemistry to make the results more reliable between different laboratories.
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Immunohistochemistry [IHC] is an important application of monoclonal as well as polyclonal antibodies to determine the tissue distribution of an antigen [protein or lipid] by specific antigen/antibody reaction tagged with a visible label. Immunohistochemistry has an expanding role in diagnostic and research laboratories. This article highlights the various applications of IHC in health and diseases and gives more information in the Future directions of immunohistochemistry.
Polyclonal antibodies
Histopathology
Histology
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Surgical oncology
Melanoma diagnosis
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Objective To discuss the application o immunohistochemistry autostainer in immunohistochemistry.Methods More than 30 kinds of first antibodies of the Pathology Department,such as AAT,CerBb-2,CK,HBcAg,ER,PR,Ki-67,and unified second antibodies were selected.Immunohistochemistry autostainer and manual operation were applied to the staining of the antibodies,and then the results by the above methods were compared.Results The antibodies stained by immunohistochemistry autostainer,gifted with clear background,no edge effect,uniform staining and accurate positive results,were all better than those by manual operation from all aspects.Conclusion Immunohistochemistry autostainer is highly automatic,time-saving,manpower-saving,repeatable and highly standardized.
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In the diagnosis of clinical pathology,immunohistochemistry(IHC) is a very important technology and tools.The immunohistochemical technique used in the pathological diagnosis started the 1970s,pathologist diagnosis of tumor classification,prognosis had a huge impact,but also extends the understanding of the people for various diseases and tumor formationpathological diagnosis and research..However,with the extensive application of immunohistochemistry,the immunohistochemical technique have some limitations.In-depth study of the principles and techniques of immunohistochemistry,familiar with all kinds of really positive antibody reaction site,and inter-laboratory standardization of immunohistochemistry,play the largest role in support of immunohistochemistry in the pathological diagnosis.This article on the above issues as follows.
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