B cell chronic lymphocytic leukaemia/small lymphocytic lymphoma: Role of ZAP70 determination on bone marrow biopsy specimens

Elena Sabattini, Rocio Orduz, Cristina Campidelli, Pier Luigi Zinzani, Vincenzo Callea, Simona Zupo, Giovanna Cutrona, Fortunato Morabito, Manlio Ferrarini, Stefano Pileri

Research output: Contribution to journalArticle

Abstract

Background: The course of chronic lymphocytic leukaemia/small lymphocytic lymphoma (CLL/SLL) partly depends on the mutational status of the variable region of immunoglobulin heavy chain genes (IgVH), which defines two subgroups of tumours: mutated and unmutated. The expression of zeta-associated protein 70 (ZAP70) is significantly associated with the more aggressive unmutated forms. Aims: To assess the feasibility of the ZAP70 immunohistochemical test on bone-marrow biopsy (BMB) specimens and to compare the results with those of western blotting (WB) and IgVH mutational status assessed on neoplastic cells from peripheral blood. Methods: 26 patients with CLL/SLL detected on BMB and with known IgVH mutational status were selected. ZAP70 was determined by immunohistochemistry (IHC) comparing three antibodies from different sources (Upstate, Cell Signaling, Santa Cruz, California, USA) and two different methods (APAAP and EnVision+). In 23 cases, ZAP70 WB results were also available. Results: ZAP70 determination on BMB specimens turned out to be easily feasible with routine procedures with reagents from Upstate and Cell Signaling. The results were concordant with those obtained with WB and mutational status analysis in >80% of the cases with both reagents. Three of four discordant cases were mutated/ZAP70 positive, with two staining weakly for ZAP70 on both WB and IHC. Conclusions: The study confirms the role of ZAP70 as a possible surrogate of mutational status and emphasises its application in routine diagnostics; it discloses a small subset of discordant cases (mutated/ZAP70 weakly positive) that clinically cluster with the more favourable forms.

Original languageEnglish
Pages (from-to)627-632
Number of pages6
JournalJournal of Clinical Pathology
Volume60
Issue number6
DOIs
Publication statusPublished - Jun 2007

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B-Cell Chronic Lymphocytic Leukemia
Bone Marrow
Biopsy
Proteins
Western Blotting
Immunohistochemistry
Immunoglobulin Heavy Chain Genes
Blood Cells
Staining and Labeling
Antibodies

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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B cell chronic lymphocytic leukaemia/small lymphocytic lymphoma : Role of ZAP70 determination on bone marrow biopsy specimens. / Sabattini, Elena; Orduz, Rocio; Campidelli, Cristina; Zinzani, Pier Luigi; Callea, Vincenzo; Zupo, Simona; Cutrona, Giovanna; Morabito, Fortunato; Ferrarini, Manlio; Pileri, Stefano.

In: Journal of Clinical Pathology, Vol. 60, No. 6, 06.2007, p. 627-632.

Research output: Contribution to journalArticle

Sabattini, Elena ; Orduz, Rocio ; Campidelli, Cristina ; Zinzani, Pier Luigi ; Callea, Vincenzo ; Zupo, Simona ; Cutrona, Giovanna ; Morabito, Fortunato ; Ferrarini, Manlio ; Pileri, Stefano. / B cell chronic lymphocytic leukaemia/small lymphocytic lymphoma : Role of ZAP70 determination on bone marrow biopsy specimens. In: Journal of Clinical Pathology. 2007 ; Vol. 60, No. 6. pp. 627-632.
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T1 - B cell chronic lymphocytic leukaemia/small lymphocytic lymphoma

T2 - Role of ZAP70 determination on bone marrow biopsy specimens

AU - Sabattini, Elena

AU - Orduz, Rocio

AU - Campidelli, Cristina

AU - Zinzani, Pier Luigi

AU - Callea, Vincenzo

AU - Zupo, Simona

AU - Cutrona, Giovanna

AU - Morabito, Fortunato

AU - Ferrarini, Manlio

AU - Pileri, Stefano

PY - 2007/6

Y1 - 2007/6

N2 - Background: The course of chronic lymphocytic leukaemia/small lymphocytic lymphoma (CLL/SLL) partly depends on the mutational status of the variable region of immunoglobulin heavy chain genes (IgVH), which defines two subgroups of tumours: mutated and unmutated. The expression of zeta-associated protein 70 (ZAP70) is significantly associated with the more aggressive unmutated forms. Aims: To assess the feasibility of the ZAP70 immunohistochemical test on bone-marrow biopsy (BMB) specimens and to compare the results with those of western blotting (WB) and IgVH mutational status assessed on neoplastic cells from peripheral blood. Methods: 26 patients with CLL/SLL detected on BMB and with known IgVH mutational status were selected. ZAP70 was determined by immunohistochemistry (IHC) comparing three antibodies from different sources (Upstate, Cell Signaling, Santa Cruz, California, USA) and two different methods (APAAP and EnVision+). In 23 cases, ZAP70 WB results were also available. Results: ZAP70 determination on BMB specimens turned out to be easily feasible with routine procedures with reagents from Upstate and Cell Signaling. The results were concordant with those obtained with WB and mutational status analysis in >80% of the cases with both reagents. Three of four discordant cases were mutated/ZAP70 positive, with two staining weakly for ZAP70 on both WB and IHC. Conclusions: The study confirms the role of ZAP70 as a possible surrogate of mutational status and emphasises its application in routine diagnostics; it discloses a small subset of discordant cases (mutated/ZAP70 weakly positive) that clinically cluster with the more favourable forms.

AB - Background: The course of chronic lymphocytic leukaemia/small lymphocytic lymphoma (CLL/SLL) partly depends on the mutational status of the variable region of immunoglobulin heavy chain genes (IgVH), which defines two subgroups of tumours: mutated and unmutated. The expression of zeta-associated protein 70 (ZAP70) is significantly associated with the more aggressive unmutated forms. Aims: To assess the feasibility of the ZAP70 immunohistochemical test on bone-marrow biopsy (BMB) specimens and to compare the results with those of western blotting (WB) and IgVH mutational status assessed on neoplastic cells from peripheral blood. Methods: 26 patients with CLL/SLL detected on BMB and with known IgVH mutational status were selected. ZAP70 was determined by immunohistochemistry (IHC) comparing three antibodies from different sources (Upstate, Cell Signaling, Santa Cruz, California, USA) and two different methods (APAAP and EnVision+). In 23 cases, ZAP70 WB results were also available. Results: ZAP70 determination on BMB specimens turned out to be easily feasible with routine procedures with reagents from Upstate and Cell Signaling. The results were concordant with those obtained with WB and mutational status analysis in >80% of the cases with both reagents. Three of four discordant cases were mutated/ZAP70 positive, with two staining weakly for ZAP70 on both WB and IHC. Conclusions: The study confirms the role of ZAP70 as a possible surrogate of mutational status and emphasises its application in routine diagnostics; it discloses a small subset of discordant cases (mutated/ZAP70 weakly positive) that clinically cluster with the more favourable forms.

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