Application of tissue microarray technology to the study of non-Hodgkin's and Hodgkin's lymphoma.

The immunohistochemical analysis of lymphoid neoplasms has led to refined classification schemes based on the profile of antigen expression and correlation with morphological, cytogenetic, molecular, and clinical features. Tissue microarrays (TMAs) are a powerful tool to rapidly characterize the phenotypic profile of a large number of samples. We show that this technique can be readily applied to the study of lymphoma by examining the expression profile of a series of 193 B-cell non-Hodgkin's lymphomas (NHLs) and 29 Hodgkin's lymphomas (HLs) using immunohistochemistry and in situ hybridization (ISH). The NHL cases were studied for the expression of commonly used markers-including CD3, CD5, CD10, CD20, CD23, CD30, CD43, Bcl-2, and cyclin D1 by immunohistochemical staining of TMAs-and these results were compared with whole sections (WS) of the same cases. We found a high degree of correlation between the results achieved with TMAs or WS (86% to 100% of cases). P53 and MIB-1 staining were studied, and the results were similar to that reported in the literature. HL cases were stained for CD20, CD30, CD15 (LeuM1), and latent membrane protein 1 expression, and ISH was performed using probes for EBER-1 and-2 transcripts. The results from HL cases on TMA sections matched exactly with those of WS. We correlated cytogenetic results with immunohistochemical stains and morphology in cases of mantle cell lymphoma [t(11;14)(q13;q32)] and follicular lymphoma [t(14;18)(q32;q24)]. This extensive expression profile of B-cell NHLs and HL tissues discloses the ability of TMAs to rapidly screen a large series of cases and represents the first report of method validation for this technique in the study of lymphoma.

[1]  C. Cordon-Cardo,et al.  Validation of tissue microarrays for immunohistochemical profiling of cancer specimens using the example of human fibroblastic tumors. , 2001, The American journal of pathology.

[2]  D. Arber,et al.  Frequency of bcl-2 expression in non-Hodgkin's lymphoma: a study of 778 cases with comparison of marginal zone lymphoma and monocytoid B-cell hyperplasia. , 1998, Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc.

[3]  T. Yoshino,et al.  Reduction of hematopoietic cell-specific tyrosine phosphatase SHP-1 gene expression in natural killer cell lymphoma and various types of lymphomas/leukemias : combination analysis with cDNA expression array and tissue microarray. , 2001, The American journal of pathology.

[4]  S. Hamilton-Dutoit,et al.  Expression of Epstein-Barr virus latent gene products in tumour cells of Hodgkin's disease , 1991, The Lancet.

[5]  S. Perkins,et al.  Decreased CD10 expression in grade III and in interfollicular infiltrates of follicular lymphomas. , 2001, American journal of clinical pathology.

[6]  J. Kononen,et al.  Tissue microarrays for high-throughput molecular profiling of tumor specimens , 1998, Nature Medicine.

[7]  D. Hossfeld E.S. Jaffe, N.L. Harris, H. Stein, J.W. Vardiman (eds). World Health Organization Classification of Tumours: Pathology and Genetics of Tumours of Haematopoietic and Lymphoid Tissues , 2002 .

[8]  D. Arber,et al.  CD10: A Review , 1997 .

[9]  Bernard R. Rosner,et al.  Fundamentals of Biostatistics. , 1992 .

[10]  R. Warnke,et al.  Proliferative rates of non-Hodgkin's lymphomas as assessed by Ki-67 antibody. , 1987, Human pathology.

[11]  D. Rimm,et al.  Validation of Tissue Microarray Technology in Breast Carcinoma , 2000, Laboratory Investigation.

[12]  Yasodha Natkunam,et al.  Analysis of MUM1/IRF4 Protein Expression Using Tissue Microarrays and Immunohistochemistry , 2001, Modern Pathology.

[13]  C. Cordon-Cardo,et al.  p63 expression profiles in human normal and tumor tissues. , 2002, Clinical cancer research : an official journal of the American Association for Cancer Research.

[14]  R S Chaganti,et al.  BCL8, a novel gene involved in translocations affecting band 15q11-13 in diffuse large-cell lymphoma. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[15]  M. Ladanyi,et al.  MYC rearrangement and translocations involving band 8q24 in diffuse large cell lymphomas. , 1991, Blood.

[16]  E. Jaffe,et al.  Macrophage-Derived Chemokine Expression in Classical Hodgkin's Lymphoma: Application of Tissue Microarrays , 2001, Modern Pathology.

[17]  K. Chang,et al.  Frequency of CD43 expression in non-Hodgkin lymphoma. A survey of 742 cases and further characterization of rare CD43+ follicular lymphomas. , 1999, American journal of clinical pathology.

[18]  P. Koduru,et al.  Correlation between mutation in P53, p53 expression, cytogenetics, histologic type, and survival in patients with B-cell non-Hodgkin's lymphoma. , 1997, Blood.

[19]  J. Lasota,et al.  Bcl‐2 oncoprotein is widespread in lymphoid tissue and lymphomas but its differential expression in benign versus malignant follicles and monocytoid B‐cell proliferations is of diagnostic value , 1995, APMIS : acta pathologica, microbiologica, et immunologica Scandinavica.