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

doi:10.1053/hupa.2002.127438

Human Pathology

Volume 33, Issue 10, October 2002, Pages 968-974

https://doi.org/10.1053/hupa.2002.127438 Get rights and content

Abstract

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. HUM PATHOL 33:968-974. Copyright 2002, Elsevier Science (USA). All rights reserved.

Section snippets

Case selection

Lymph node biopsy specimens were retrieved from the pathology files of the Department of Pathology at Memorial Sloan-Kettering Cancer Center. A total of 202 NHLs—including chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL, n = 10), FL (n = 152), diffuse large B-cell lymphoma (DLCL, n = 27), MCL (n = 8), and marginal zone lymphoma (MZL, n = 5)—were selected and studied. A total of 34 HL cases—characterized as nodular lymphocyte predominant (NLP, n = 6), mixed cellularity (MC, n =

Chronic lymphocytic leukemia/small lymphocytic leukemia

We evaluated 9 CLLs with our immunohistochemical panel using TMA sections (Table 1, Fig 2A).

. TMAs show the immunohistochemical profile of NHL and HL cases. (A) TMA cores from representative NHL cases. Upper panel: chronic lymphocytic leukemia (top row), mantle cell lymphoma (middle row), and marginal zone lymphoma (bottom row). Lower panel: diffuse large B-cell lymphoma (top row) and follicular lymphoma (bottom row). (Original magnification × 100 [first hematoxylin and eosin] and × 400.) (B) HL

Discussion

The intensive investigation into the pathobiology of lymphoid neoplasms has led to the detailed characterization of the immunophenotypic profiles of these tumors. Many reagents are now available for use in archival material that aid in their classification of these neoplasms based on their antigen expression. We applied high-throughput TMAs to study NHL and HL lymphomas, and we showed that this technique can be used reliably to characterize protein and mRNA expression. We performed a series of

Acknowledgements

The authors thank Miriam Fayed, Dr. Carlos Cordon-Cardo, and Janet Brownstein for their helpful contribution to this work.

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^*: Supported in part by National Institutes of Health Grant No. HL-04478 (CVH).

^**: Address correspondence and reprint requests to Julie Teruya-Feldstein, MD, Department of Pathology, Memorial Sloan-Kettering Cancer Center, 1275 York Ave, New York, NY 10021.

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Original ContributionsApplication of tissue microarray technology to the study of non-Hodgkin's and Hodgkin's lymphoma*,**

Abstract

Section snippets

Case selection

Chronic lymphocytic leukemia/small lymphocytic leukemia

Discussion

Acknowledgements

Mod Pathol

Am J Pathol

Lab Invest

Am J Pathol

Mod Pathol

Blood

Blood

Hum Pathol

Lancet

Original Contributions
Application of tissue microarray technology to the study of non-Hodgkin's and Hodgkin's lymphoma*,**