Sources/Clones
Rabbit polyclonal antibody (Nichirei Corporation, Japan).
Fixation/Preparation
This antibody is suitable for formalin-fixed paraffin sections. Microwave antigen retrieval is essential for immunoreaction.
Background
It was recently recognized that a translocation involving chromosome 2 and 5 was associated with anaplastic large cell lymphoma (ALCL) (Mason et al, 1990). However, the exact frequency of this association is not clear. The translocation breakpoint has been cloned with the candidate genes being identified as the nucleophosmin (NPM) gene on chromosome 5 and a putative tyrosine kinase gene, the appropriately named anaplastic lymphoma kinase (ALK) gene, on chromosome 2 (Morris et al, 1994). It has been postulated that the ectopic expression of ALK may contribute to the pathogenesis of ALCL, but the ability of ALK to transform hematopoietic cells has not yet been demonstrated experimentally. The cloning of the translocation breakpoint allows the demonstration of the t(2:5) (p23; q35) by techniques other than cytogenetics. This has permitted the demonstration of t(2;5) in 30% (89/297) of ALCL cases (for review, see Chan, 1996) from several studies. In addition t(2;5) was also demonstrated in 6% (21/345) of Hodgkin's disease cases. The significance of the latter has yet to be determined.
Shiota et al (1994) produced a rabbit polyclonal antibody (anti-p80) against the tyrosine kinase domain of ALK in the ALK-NPM fusion protein. In tonsils, only follicular dendritic cells and endothelial cells showed weak positive signals when immunostained with anti-p80. Of 50 lymphomas, only three cases of ALCL with t(2;5) (p23;q35) and p80 mRNA reacted with the antibody. Several subsequent studies have confirmed the sensitivity and specificity of anti-p80 in identifying ALCL expressing ALK. The incidence of Hodgkin's disease that are t(2;5) positive also appears to be very low (3/186) by immunohistochemical study using anti-p80 (Lamant et al, 1996).
Applications
Currently, anti-p80 appears to be the most well-characterized antibody for the identification of ALCL with t(2;5). Given the morphological heterogeneity of ALCL, this antibody would prove to be useful in confirming the diagnosis, albeit in approximately a third of cases (Shiota et al, 1995).
Comments
The cloning of the t(2;5) (p23; q35) has stimulated interest in studying this translocation in ALCL and Hodgkin's disease. The availability of a specific antibody to ALK not only facilitates the diagnosis of ALCL in pathology laboratories using routine immunohistochemical procedures, but may contribute to a greater understanding of the significance of t(2;5) in the pathogenesis of the heterogeneous nature of ALCL (Pittaluga et al, 1997).
References
•Chan WC 1996. The t(2;5) or NPM-ALK translocation in lymphomas: diagnostic considerations. Advances in Anatomical Pathology 3: 396-399.
•80 immunostaining. Blood 87:284-291.
•Mason DY, Bastard C, Rimokh R et al 1990. CD30-positive large cell lymphomas (`Ki-1 lymphoma') are associated with a chromosomal translocation involving 5q35. British Journal of Haematology 74: 161-168.
•Morris SW, Kirstein MN, Valentine MB et al 1994. Fusion of a kinase gene, ALK to a nucleolar protein gene NPM, in non-Hodgkin's lymphoma. Science 263: 1281-1284.
•Pittaluga S, Wlodarska I, Pulford K et al 1997. The monoclonal antibody ALK1 identifies a distinct morphological subset of anaplastic large cell lymphoma associated with 2p23/ALK rearrangements. American Journal of Pathology 151:343-351.
•Shiota M, Fujimoto J, Takenaga M et al. 1944 Diagnosis of t(2;5) (p23; q35)-associated Ki-1 lymphoma with immunohistochemistry. Blood 84:3648-3652.
•Shiota M, Nakamura S, Ichinohasama R et al 1995. Anaplastic large cell lymphomas expressing the novel chimeric protein p80NPM/ALK. A distinct clinicopathologic entity. Blood 86:1954-1960.
Bibliografia
Manual of diagnostic antibodies for immunohistology / Anthony S.-Y. Leong, Kumarasen Cooper, F. Joel W.-M. Leong.
Rabbit polyclonal antibody (Nichirei Corporation, Japan).
Fixation/Preparation
This antibody is suitable for formalin-fixed paraffin sections. Microwave antigen retrieval is essential for immunoreaction.
Background
It was recently recognized that a translocation involving chromosome 2 and 5 was associated with anaplastic large cell lymphoma (ALCL) (Mason et al, 1990). However, the exact frequency of this association is not clear. The translocation breakpoint has been cloned with the candidate genes being identified as the nucleophosmin (NPM) gene on chromosome 5 and a putative tyrosine kinase gene, the appropriately named anaplastic lymphoma kinase (ALK) gene, on chromosome 2 (Morris et al, 1994). It has been postulated that the ectopic expression of ALK may contribute to the pathogenesis of ALCL, but the ability of ALK to transform hematopoietic cells has not yet been demonstrated experimentally. The cloning of the translocation breakpoint allows the demonstration of the t(2:5) (p23; q35) by techniques other than cytogenetics. This has permitted the demonstration of t(2;5) in 30% (89/297) of ALCL cases (for review, see Chan, 1996) from several studies. In addition t(2;5) was also demonstrated in 6% (21/345) of Hodgkin's disease cases. The significance of the latter has yet to be determined.
Shiota et al (1994) produced a rabbit polyclonal antibody (anti-p80) against the tyrosine kinase domain of ALK in the ALK-NPM fusion protein. In tonsils, only follicular dendritic cells and endothelial cells showed weak positive signals when immunostained with anti-p80. Of 50 lymphomas, only three cases of ALCL with t(2;5) (p23;q35) and p80 mRNA reacted with the antibody. Several subsequent studies have confirmed the sensitivity and specificity of anti-p80 in identifying ALCL expressing ALK. The incidence of Hodgkin's disease that are t(2;5) positive also appears to be very low (3/186) by immunohistochemical study using anti-p80 (Lamant et al, 1996).
Applications
Currently, anti-p80 appears to be the most well-characterized antibody for the identification of ALCL with t(2;5). Given the morphological heterogeneity of ALCL, this antibody would prove to be useful in confirming the diagnosis, albeit in approximately a third of cases (Shiota et al, 1995).
Comments
The cloning of the t(2;5) (p23; q35) has stimulated interest in studying this translocation in ALCL and Hodgkin's disease. The availability of a specific antibody to ALK not only facilitates the diagnosis of ALCL in pathology laboratories using routine immunohistochemical procedures, but may contribute to a greater understanding of the significance of t(2;5) in the pathogenesis of the heterogeneous nature of ALCL (Pittaluga et al, 1997).
References
•Chan WC 1996. The t(2;5) or NPM-ALK translocation in lymphomas: diagnostic considerations. Advances in Anatomical Pathology 3: 396-399.
•80 immunostaining. Blood 87:284-291.
•Mason DY, Bastard C, Rimokh R et al 1990. CD30-positive large cell lymphomas (`Ki-1 lymphoma') are associated with a chromosomal translocation involving 5q35. British Journal of Haematology 74: 161-168.
•Morris SW, Kirstein MN, Valentine MB et al 1994. Fusion of a kinase gene, ALK to a nucleolar protein gene NPM, in non-Hodgkin's lymphoma. Science 263: 1281-1284.
•Pittaluga S, Wlodarska I, Pulford K et al 1997. The monoclonal antibody ALK1 identifies a distinct morphological subset of anaplastic large cell lymphoma associated with 2p23/ALK rearrangements. American Journal of Pathology 151:343-351.
•Shiota M, Fujimoto J, Takenaga M et al. 1944 Diagnosis of t(2;5) (p23; q35)-associated Ki-1 lymphoma with immunohistochemistry. Blood 84:3648-3652.
•Shiota M, Nakamura S, Ichinohasama R et al 1995. Anaplastic large cell lymphomas expressing the novel chimeric protein p80NPM/ALK. A distinct clinicopathologic entity. Blood 86:1954-1960.
Bibliografia
Manual of diagnostic antibodies for immunohistology / Anthony S.-Y. Leong, Kumarasen Cooper, F. Joel W.-M. Leong.
