Validation of tissue microarray immunohistochemistry staining and interpretation in diffuse large B-cell lymphoma

Youli Zu, Seth M. Steinberg, Elias Campo, Christine P. Hans, Dennis D. Weisenburger, Rita Braziel, Jan Delabie, Randy D. Gascoyne, Konrad Muller-Hermlink, Stefania Pittaluga, Mark Raffeld, Wing C. Chan, Elaine S. Jaffe

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Abstract

Tissue microarrays (TMAs) show concordance with whole tissue sections in the immunohistochemical evaluation of tumor cells. However, potential inter-institutional variability among observers and immunohistochemical staining methods has not been fully addressed. We selected 21 cases of diffuse large B-cell lymphoma (DLBCL) to process for TMAs. Immunohistochemical stains were performed in 3 laboratories, and reviewed independently by 3 hematopathologists at the 3 institutions. Stains were scored on a 4-point scale. Statistical analyses of variation in the scoring among observers and among different institutions' stains were performed. Stains for CD3, CD10, CD20, BCL-2, BCL-6, MIB-1, and FOX-P1 revealed little variation among observers, with an average 51-82% complete agreement and 82-100% agreement ± 1 numerical score. The rate of concordance when evaluating most stains performed in different laboratories was also relatively good, with an average of 55-72% complete agreement and 70-97% agreement ± 1 score. However, scoring of MUM-1 and p53 stains showed wider variation, with an average of only 37 and 30% complete agreement among observers, and 11 and 45% agreement when stains from different institutions were examined. Further statistical analyses were performed to compare the observers' scoring of their own institution's stains (self-review) vs. observers' scoring of other institutions' stains (non-self). The agreement rate for the p53 stain was significantly higher when based on self-review (average 58% complete agreement) compared with an agreement rate of only 10.5% when based on a review of stains performed in another laboratory, non-self review, P <0.01. This difference in the self- vs. non-self review was not seen when data for MUM-1 were analysed. In conclusion, most phenotypic markers used in the analysis of DLBCL can be evaluated in TMAs with adequate agreement among observers and laboratories. These include CD3, CD20, CD10, BCL-2, BCL-6, MIB-1, and FOX-P1. However, some markers, such as p53 and MUM-1, are more prone to inter-institutional variation. Variations in interpretation can be partially overcome by self-adjusted/adapt tendency, as seen with p53. Especially with newly developed markers, such as MUM-1, the development of standardized techniques for staining and interpretation is critical to reduce inter-observer variability.

Original languageEnglish (US)
Pages (from-to)693-701
Number of pages9
JournalLeukemia and Lymphoma
Volume46
Issue number5
DOIs
StatePublished - May 2005

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Lymphoma, Large B-Cell, Diffuse
Coloring Agents
Immunohistochemistry
Staining and Labeling
Observer Variation

Keywords

  • Diffuse large B-cell lymphoma
  • Immunohistochemistry
  • Monoclonal antibodies
  • Prognostic markers
  • Tissue microarray
  • Validation

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research

Cite this

Validation of tissue microarray immunohistochemistry staining and interpretation in diffuse large B-cell lymphoma. / Zu, Youli; Steinberg, Seth M.; Campo, Elias; Hans, Christine P.; Weisenburger, Dennis D.; Braziel, Rita; Delabie, Jan; Gascoyne, Randy D.; Muller-Hermlink, Konrad; Pittaluga, Stefania; Raffeld, Mark; Chan, Wing C.; Jaffe, Elaine S.

In: Leukemia and Lymphoma, Vol. 46, No. 5, 05.2005, p. 693-701.

Research output: Contribution to journalArticle

Zu, Y, Steinberg, SM, Campo, E, Hans, CP, Weisenburger, DD, Braziel, R, Delabie, J, Gascoyne, RD, Muller-Hermlink, K, Pittaluga, S, Raffeld, M, Chan, WC & Jaffe, ES 2005, 'Validation of tissue microarray immunohistochemistry staining and interpretation in diffuse large B-cell lymphoma', Leukemia and Lymphoma, vol. 46, no. 5, pp. 693-701. https://doi.org/10.1080/10428190500051844
Zu, Youli ; Steinberg, Seth M. ; Campo, Elias ; Hans, Christine P. ; Weisenburger, Dennis D. ; Braziel, Rita ; Delabie, Jan ; Gascoyne, Randy D. ; Muller-Hermlink, Konrad ; Pittaluga, Stefania ; Raffeld, Mark ; Chan, Wing C. ; Jaffe, Elaine S. / Validation of tissue microarray immunohistochemistry staining and interpretation in diffuse large B-cell lymphoma. In: Leukemia and Lymphoma. 2005 ; Vol. 46, No. 5. pp. 693-701.
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AU - Steinberg, Seth M.

AU - Campo, Elias

AU - Hans, Christine P.

AU - Weisenburger, Dennis D.

AU - Braziel, Rita

AU - Delabie, Jan

AU - Gascoyne, Randy D.

AU - Muller-Hermlink, Konrad

AU - Pittaluga, Stefania

AU - Raffeld, Mark

AU - Chan, Wing C.

AU - Jaffe, Elaine S.

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N2 - Tissue microarrays (TMAs) show concordance with whole tissue sections in the immunohistochemical evaluation of tumor cells. However, potential inter-institutional variability among observers and immunohistochemical staining methods has not been fully addressed. We selected 21 cases of diffuse large B-cell lymphoma (DLBCL) to process for TMAs. Immunohistochemical stains were performed in 3 laboratories, and reviewed independently by 3 hematopathologists at the 3 institutions. Stains were scored on a 4-point scale. Statistical analyses of variation in the scoring among observers and among different institutions' stains were performed. Stains for CD3, CD10, CD20, BCL-2, BCL-6, MIB-1, and FOX-P1 revealed little variation among observers, with an average 51-82% complete agreement and 82-100% agreement ± 1 numerical score. The rate of concordance when evaluating most stains performed in different laboratories was also relatively good, with an average of 55-72% complete agreement and 70-97% agreement ± 1 score. However, scoring of MUM-1 and p53 stains showed wider variation, with an average of only 37 and 30% complete agreement among observers, and 11 and 45% agreement when stains from different institutions were examined. Further statistical analyses were performed to compare the observers' scoring of their own institution's stains (self-review) vs. observers' scoring of other institutions' stains (non-self). The agreement rate for the p53 stain was significantly higher when based on self-review (average 58% complete agreement) compared with an agreement rate of only 10.5% when based on a review of stains performed in another laboratory, non-self review, P <0.01. This difference in the self- vs. non-self review was not seen when data for MUM-1 were analysed. In conclusion, most phenotypic markers used in the analysis of DLBCL can be evaluated in TMAs with adequate agreement among observers and laboratories. These include CD3, CD20, CD10, BCL-2, BCL-6, MIB-1, and FOX-P1. However, some markers, such as p53 and MUM-1, are more prone to inter-institutional variation. Variations in interpretation can be partially overcome by self-adjusted/adapt tendency, as seen with p53. Especially with newly developed markers, such as MUM-1, the development of standardized techniques for staining and interpretation is critical to reduce inter-observer variability.

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