THE EXPRESSION OF THE ONCOGENE PRODUCT BCL-2, TUMORSUPPRESSOR GENE PRODUCT P53 AND TUMOR CELL PROLIFERATION MARKERS PCNA AND KI-67 IN 85 CASES OF NON-HODGKIN'S LYMPHOMA
Many gene abnormalities have been detected in malignant lymphomas. In order to analyze the pathological grading of malignant lymphoma, we investigated the expression of bcl-2 protein due to the t (14 ; 18) translocation and the expression of mutated type-p53 protein due to the point mutations in the...
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| Published in | Journal of The Showa Medical Association Vol. 60; no. 1; pp. 93 - 103 |
|---|---|
| Main Authors | , , , |
| Format | Journal Article |
| Language | English Japanese |
| Published |
The Showa University Society
28.02.2000
昭和大学学士会 |
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| Online Access | Get full text |
| ISSN | 0037-4342 2185-0976 |
| DOI | 10.14930/jsma1939.60.93 |
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| Abstract | Many gene abnormalities have been detected in malignant lymphomas. In order to analyze the pathological grading of malignant lymphoma, we investigated the expression of bcl-2 protein due to the t (14 ; 18) translocation and the expression of mutated type-p53 protein due to the point mutations in the tumor suppressor gene, p53 which is located on chromosome 17p13.1. We also examined the cell proliferation profile immunohistochemically by using proliferating cell nuclear antigen (PCNA) and Ki-67 as proliferating cell markers. Twenty patients with responsive lymph node lesions (that is, reactive lymphadenopathy) and 85 patients with non-Hodgkin's lymphoma were used as subjects in this study. Bcl-2 protein was expressed in follicular lymphomas at a high frequency, whereas all cases of follicular centrocytes in the responsive lesions were negative, indicating that Bcl-2 is a very important marker to distinguish follicular lymphoma from reactive lymphadenopathy. PCNA and Ki-67 as well as p53 were good markers to evaluate the degree of histological malignancy of non-Hodgkin's lymphoma. |
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| AbstractList | Many gene abnormalities have been detected in malignant lymphomas. In order to analyze the pathological grading of malignant lymphoma, we investigated the expression of bcl-2 protein due to the t (14 ; 18) translocation and the expression of mutated type-p53 protein due to the point mutations in the tumor suppressor gene, p53 which is located on chromosome 17p13.1. We also examined the cell proliferation profile immunohistochemically by using proliferating cell nuclear antigen (PCNA) and Ki-67 as proliferating cell markers. Twenty patients with responsive lymph node lesions (that is, reactive lymphadenopathy) and 85 patients with non-Hodgkin's lymphoma were used as subjects in this study. Bcl-2 protein was expressed in follicular lymphomas at a high frequency, whereas all cases of follicular centrocytes in the responsive lesions were negative, indicating that Bcl-2 is a very important marker to distinguish follicular lymphoma from reactive lymphadenopathy. PCNA and Ki-67 as well as p53 were good markers to evaluate the degree of histological malignancy of non-Hodgkin's lymphoma. Many gene abnormalities have been detected in malignant lymphomas. In order to analyze the pathological grading of malignant lymphoma, we investigated the expression of bcl-2 protein due to the t (14 ; 18) translocation and the expression of mutated type-p53 protein due to the point mutations in the tumor suppressor gene, p53 which is located on chromosome 17p13.1. We also examined the cell proliferation profile immunohistochemically by using proliferating cell nuclear antigen (PCNA) and Ki-67 as proliferating cell markers. Twenty patients with responsive lymph node lesions (that is, reactive lymphadenopathy) and 85 patients with non-Hodgkin's lymphoma were used as subjects in this study. Bcl-2 protein was expressed in follicular lymphomas at a high frequency, whereas all cases of follicular centrocytes in the responsive lesions were negative, indicating that Bcl-2 is a very important marker to distinguish follicular lymphoma from reactive lymphadenopathy. PCNA and Ki-67 as well as p53 were good markers to evaluate the degree of histological malignancy of non-Hodgkin's lymphoma. 悪性リンパ腫における遺伝子異常が多く発見されている.我々は悪性リンパ腫の病態解析を目的とし, t (14; 18) によるbcl-2蛋白の過剰発現と, 17p欠失によって生じる変異型p53蛋白の発現, 更に細胞増殖能 (増殖細胞マーカーとしてPCNA, Ki-67を用いる) について免疫組織化学的およびPCR (polymerase chain reaction) 法により検討を行った.対象は当院における反応性リンパ節病変20例, 非ポジキンリンパ腫85例である.bcl-2蛋白の発現は濾胞性リンパ腫において高率で, 反応性病変の濾胞芽中心の細胞は全例陰性であった.したがってbcl-2は濾胞性リンパ腫と反応性病変との鑑別に有用なマーカーであった.増殖マーカーであるproliferating cell nuclear antigen (PCNA) , Ki-67, またp53遺伝子の異常による蛋白発現は非ポジキンリンパ腫の組織学的悪性度を反映する生物学的因子であると考えられた. |
| Author | SUZUKI, Takao MITSUYA, Toshiyuki KISHIMOTO, Koji TATE, Genshu |
| Author_FL | 楯 玄秀 岸本 浩次 光谷 俊幸 鈴木 孝夫 |
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| DocumentTitle_FL | 悪性リンパ腫における遺伝子産物発現と細胞増殖能の検討 ―bcl-2, p53, PCNA, ki-67の発現について |
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| References | 17) Amakawa R, Fukuhara S, Ohno H, et al: Involvement of bcl-2 gene in Japanese follicular lymphoma. Blood 73 : 787-791, 1989. 16) Lee MS, Blick MB, Pathak S, et al: The gene located at chromosome 18q21 is rearranged in uncultured diffuse lymphomas as well as follicular lymphomas. Blood 70 : 90-95, 1987. 12) Cleary M, Smith S and Sklar J : Cloning and structural analysis of cDNAs for bcl-2 and a hybrid bcl-2/immunoglobulin transcript resulting from the t (14 ; 18) translocation. Cell 47 : 19-28, 1986. 14) Hochenbery D, Nunez G, Milliman C, et al: Bcl-2 is an inner mitochondrial membrane protein that blocks programmed cell death. Nature 348 : 334-336, 1990. 19) 田崎和洋: 中細胞型Bリンパ腫の組織発生に関する免疫組織化学的・遺伝子学的検討-bcl-1, bc1-2遺伝子を中心に-. 日網内系学会誌33 : 41-57, 1993. 26) Krajewski S, Gascoyne RD, Zapata JM, et al : Immunolocalization of the ICE/ Ced-3-f amily protease, CPP32 (Caspase-3) , in non-Hodgkin's lymphomas, chronic lymphocytic leukemias, and reactive lymph nodes. Blood 89 : 3817-3825, 1997. 15) Weiss LM, Warnke RA, Sklar J, et al: Molecular analysis of the t (14; 18) chro-mosomal translocation in malignant lymphomas. N Engl J Med 317 : 1185-1189, 1987. 13) Vaux DL, Cory S and Adams JM: bcl-2 gene promotes haemopoietic cell survival and cooperates with c-myc to immortalize pre-B cells. Nature 335 : 440-442, 1988. 5) Jaf f e ES, Harris NL, Diebold J, et al: World health organization classification of neoplastic disease of the hematopoietic and lymphoid tissue. Progress report. Am J Clin Pat hol 111 (Suppl) : S8-12, 1999. 27) Levine AJ : The tumor suppressor genes. Annu Rev Biochem 62 : 623-651, 1993. 3) Lennert K and Feller AC: Histopathology of non-Hodgkin's Lymphomas (Based on the up dated Kiel classification) . 2nd ed, Springer-Velag, Berlin, 1990. 18) 瀬戸加大, 長田啓隆: リンパ腫におけるbcl-2遺伝子の役割. 臨血 32 : 644-649, 1991. 8) Fifth International Workshop on Chromosomes in Leukemia-Lymphoma: Correlation chromosome abnormalities with histologic and immunologic characteristics in non-Hodgkin's lymphoma and adult T cell leukemia-lymphoma. Blood 70 : 1554-1564, 1987. 24) Krajewski S, Bodrug S, Gascoyne R, et al: Immunohistochemical analysis of bcl-1 and bcl-2 proteins in normal and neoplastic lymph nodes. Am J Pathol 145 : 515-525, 1994. 21) 橋本嘉幸: アポトーシス概説 (そのがんとの関係) . 蛋白質核酸酵素 38 : 101-108, 1993. 23) Knajewski S, Kanajewska M, Shabaik A, et al : Immunohistochemical analysis of in vivo patterns of Bcl-X expression. Cancer Res 54 : 5501-5507, 1994. 1) Suchi T, Tajima K, Nanba K, et al: Some problems on the histopathological diagnosis of non-Hodgkin's malignant lymhoma. A proposal of a new type. Acta Pathol Jpn 29 : 755-776, 1979. 22) Yoshino T, Kondo E, Akagi T, et al: Inverse expression of bcl-2 protein and Fas antigen in lymphoblasts in peripheral lymph nodes and activated peripheral blood T-and B-lymphocytes. Blood 83 : 1856-1861, 1994. 11) Bakhshi A, Jensen JP, Goldman P, et al: Cloning the chromosomal breakpoint of t (14; 18) human lymphomas : clustering around Jn on chromosome 14 and near a transcriptional unit on 18. Cell 41: 899-906, 1985. 9) Croce CM : Role of chromosome translocations in human neoplasia. Cell 49 : 155-156, 1987. 2) The Non-Hodgkin's Lymphoma Pathologic Classification Project: National Cancer Institute sponsored study of classification of non-Hodgkin's lymphoma. Summary and description of a Working Formulation for Clinical Usage. Cancer 49 : 2112-2135, 1982. 4) Harris NL, Jaf f e ES, Stein H, et al: A revised European-American Classification of lymphoid neoplasms. A proposal from the International Lymphoma Study Group. Blood 84 : 1361-1392, 1994. 7) Kamel OW, Lebrun DP, Davis RE, et al: Growth fraction estimation of malignant lymphomas in f ormalin-fixed paraffinembedded tissue using anti-PCNA / Cyclin 19A2. Correlation with Ki-67 labeling. Am J Pathol 138 : 1471-1477, 1991. 6) Mitani S, Aoki N, Mori S, et al: bcl-2 gene rearrangement analysis of Japanese follicular lymphoma by polymerase chain reaction in f ormalin fixed, paraffin-embedded tissue specimen. Jpn J Cancer Res 84 : 37-41, 1993. 25) Krajewski S, Krajewska M, Shabalk A, et al: Immunohistochemical determination of in vivo distribution of Bax, a dominnt inhibitor of Bcl-2. Am J Pathol 145 : 1323-1336, 1994. 10) Tsujimoto Y, Finger LR, Croce CM, et al: Cloning the chromosome breakpoint of neoplastic B cells with the t (14; 18) chromosome translocation. Science 226 : 1097 -1099, 1984. 20) 辻本賀英: がんとbcl-2. 蛋白質核酸酵素 38 : 129-133, 1993. |
| References_xml | – reference: 4) Harris NL, Jaf f e ES, Stein H, et al: A revised European-American Classification of lymphoid neoplasms. A proposal from the International Lymphoma Study Group. Blood 84 : 1361-1392, 1994. – reference: 15) Weiss LM, Warnke RA, Sklar J, et al: Molecular analysis of the t (14; 18) chro-mosomal translocation in malignant lymphomas. N Engl J Med 317 : 1185-1189, 1987. – reference: 9) Croce CM : Role of chromosome translocations in human neoplasia. Cell 49 : 155-156, 1987. – reference: 10) Tsujimoto Y, Finger LR, Croce CM, et al: Cloning the chromosome breakpoint of neoplastic B cells with the t (14; 18) chromosome translocation. Science 226 : 1097 -1099, 1984. – reference: 27) Levine AJ : The tumor suppressor genes. Annu Rev Biochem 62 : 623-651, 1993. – reference: 2) The Non-Hodgkin's Lymphoma Pathologic Classification Project: National Cancer Institute sponsored study of classification of non-Hodgkin's lymphoma. Summary and description of a Working Formulation for Clinical Usage. Cancer 49 : 2112-2135, 1982. – reference: 23) Knajewski S, Kanajewska M, Shabaik A, et al : Immunohistochemical analysis of in vivo patterns of Bcl-X expression. Cancer Res 54 : 5501-5507, 1994. – reference: 8) Fifth International Workshop on Chromosomes in Leukemia-Lymphoma: Correlation chromosome abnormalities with histologic and immunologic characteristics in non-Hodgkin's lymphoma and adult T cell leukemia-lymphoma. Blood 70 : 1554-1564, 1987. – reference: 17) Amakawa R, Fukuhara S, Ohno H, et al: Involvement of bcl-2 gene in Japanese follicular lymphoma. Blood 73 : 787-791, 1989. – reference: 16) Lee MS, Blick MB, Pathak S, et al: The gene located at chromosome 18q21 is rearranged in uncultured diffuse lymphomas as well as follicular lymphomas. Blood 70 : 90-95, 1987. – reference: 22) Yoshino T, Kondo E, Akagi T, et al: Inverse expression of bcl-2 protein and Fas antigen in lymphoblasts in peripheral lymph nodes and activated peripheral blood T-and B-lymphocytes. Blood 83 : 1856-1861, 1994. – reference: 1) Suchi T, Tajima K, Nanba K, et al: Some problems on the histopathological diagnosis of non-Hodgkin's malignant lymhoma. A proposal of a new type. Acta Pathol Jpn 29 : 755-776, 1979. – reference: 20) 辻本賀英: がんとbcl-2. 蛋白質核酸酵素 38 : 129-133, 1993. – reference: 18) 瀬戸加大, 長田啓隆: リンパ腫におけるbcl-2遺伝子の役割. 臨血 32 : 644-649, 1991. – reference: 3) Lennert K and Feller AC: Histopathology of non-Hodgkin's Lymphomas (Based on the up dated Kiel classification) . 2nd ed, Springer-Velag, Berlin, 1990. – reference: 13) Vaux DL, Cory S and Adams JM: bcl-2 gene promotes haemopoietic cell survival and cooperates with c-myc to immortalize pre-B cells. Nature 335 : 440-442, 1988. – reference: 14) Hochenbery D, Nunez G, Milliman C, et al: Bcl-2 is an inner mitochondrial membrane protein that blocks programmed cell death. Nature 348 : 334-336, 1990. – reference: 25) Krajewski S, Krajewska M, Shabalk A, et al: Immunohistochemical determination of in vivo distribution of Bax, a dominnt inhibitor of Bcl-2. Am J Pathol 145 : 1323-1336, 1994. – reference: 5) Jaf f e ES, Harris NL, Diebold J, et al: World health organization classification of neoplastic disease of the hematopoietic and lymphoid tissue. Progress report. Am J Clin Pat hol 111 (Suppl) : S8-12, 1999. – reference: 26) Krajewski S, Gascoyne RD, Zapata JM, et al : Immunolocalization of the ICE/ Ced-3-f amily protease, CPP32 (Caspase-3) , in non-Hodgkin's lymphomas, chronic lymphocytic leukemias, and reactive lymph nodes. Blood 89 : 3817-3825, 1997. – reference: 12) Cleary M, Smith S and Sklar J : Cloning and structural analysis of cDNAs for bcl-2 and a hybrid bcl-2/immunoglobulin transcript resulting from the t (14 ; 18) translocation. Cell 47 : 19-28, 1986. – reference: 7) Kamel OW, Lebrun DP, Davis RE, et al: Growth fraction estimation of malignant lymphomas in f ormalin-fixed paraffinembedded tissue using anti-PCNA / Cyclin 19A2. Correlation with Ki-67 labeling. Am J Pathol 138 : 1471-1477, 1991. – reference: 6) Mitani S, Aoki N, Mori S, et al: bcl-2 gene rearrangement analysis of Japanese follicular lymphoma by polymerase chain reaction in f ormalin fixed, paraffin-embedded tissue specimen. Jpn J Cancer Res 84 : 37-41, 1993. – reference: 24) Krajewski S, Bodrug S, Gascoyne R, et al: Immunohistochemical analysis of bcl-1 and bcl-2 proteins in normal and neoplastic lymph nodes. Am J Pathol 145 : 515-525, 1994. – reference: 19) 田崎和洋: 中細胞型Bリンパ腫の組織発生に関する免疫組織化学的・遺伝子学的検討-bcl-1, bc1-2遺伝子を中心に-. 日網内系学会誌33 : 41-57, 1993. – reference: 21) 橋本嘉幸: アポトーシス概説 (そのがんとの関係) . 蛋白質核酸酵素 38 : 101-108, 1993. – reference: 11) Bakhshi A, Jensen JP, Goldman P, et al: Cloning the chromosomal breakpoint of t (14; 18) human lymphomas : clustering around Jn on chromosome 14 and near a transcriptional unit on 18. Cell 41: 899-906, 1985. |
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| SubjectTerms | bcl-2 Ki-67 malignant lymphoma p53 Proliferating cell nuclear antigen (PCNA) 悪性リンパ腫 |
| Title | THE EXPRESSION OF THE ONCOGENE PRODUCT BCL-2, TUMORSUPPRESSOR GENE PRODUCT P53 AND TUMOR CELL PROLIFERATION MARKERS PCNA AND KI-67 IN 85 CASES OF NON-HODGKIN'S LYMPHOMA |
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