Expression of p63 protein in anaplastic large cell lymphoma: implications for genetic subtyping

Xueju Wang, Rebecca L. Boddicker, Surendra Dasari, Jagmohan S. Sidhu, Marshall E. Kadin, William R. Macon, Stephen M. Ansell, Rhett P. Ketterling, Karen L. Rech, Andrew L. Feldman

Research output: Contribution to journalArticle

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Abstract

Anaplastic large cell lymphomas (ALCLs) are CD30-positive T-cell non-Hodgkin lymphomas that bear chromosomal rearrangements of the TP53 homologue TP63 in a subset of cases that demonstrate aggressive clinical behavior. In the present study, we examined the relationship between p63 protein expression by immunohistochemistry and the results of fluorescence in situ hybridization using TP63 probes in 116 ALCLs. We also determined the relative expression of full-length TAp63 and truncated ΔNp63 isoforms (eg, p40) in ALCL cell lines and a subset of clinical cases. Overall, 35.3% of ALCLs were positive for p63 protein. Primary cutaneous and anaplastic lymphoma kinase–negative ALCLs were positive more frequently than anaplastic lymphoma kinase–positive ALCLs (P = .0034). As previously reported, cases with TP63 gene rearrangements expressed p63 uniformly. p63 expression in nonrearranged cases was associated with extra copies of TP63 on 3q28 (P < .0001). Extra copies of TP63 correlated with extra copies of the DUSP22 locus on 6p25.3 (P < .0001). Results of immunohistochemistry, Western blotting, and RNA sequencing indicated that p63 expression in nonrearranged cases was entirely attributable to TAp63 isoforms. Taken together, these findings indicate that ALCLs without TP63 rearrangements may express TAp63 isoforms of p63 and that this expression is associated with extra copies of TP63, probably due to widespread genomic copy number abnormalities rather than focal gains. Immunohistochemistry for p63 in ALCL is not specific for TP63 rearrangements but is useful clinically as a screening test to select cases for further testing by fluorescence in situ hybridization. Immunohistochemistry for ΔNp63 (p40) is not informative in the evaluation of ALCL.

Original languageEnglish (US)
Pages (from-to)19-27
Number of pages9
JournalHuman Pathology
Volume64
DOIs
StatePublished - Jun 1 2017
Externally publishedYes

Fingerprint

Anaplastic Large-Cell Lymphoma
Proteins
Immunohistochemistry
Protein Isoforms
Fluorescence In Situ Hybridization
Lymphoma
RNA Sequence Analysis
Gene Rearrangement
T-Cell Lymphoma
Non-Hodgkin's Lymphoma
Western Blotting
Cell Line
Skin

Keywords

  • Anaplastic large cell lymphoma
  • Copy number abnormality
  • Fluorescence in situ hybridization
  • p40
  • p63
  • TP63

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Expression of p63 protein in anaplastic large cell lymphoma : implications for genetic subtyping. / Wang, Xueju; Boddicker, Rebecca L.; Dasari, Surendra; Sidhu, Jagmohan S.; Kadin, Marshall E.; Macon, William R.; Ansell, Stephen M.; Ketterling, Rhett P.; Rech, Karen L.; Feldman, Andrew L.

In: Human Pathology, Vol. 64, 01.06.2017, p. 19-27.

Research output: Contribution to journalArticle

Wang, X, Boddicker, RL, Dasari, S, Sidhu, JS, Kadin, ME, Macon, WR, Ansell, SM, Ketterling, RP, Rech, KL & Feldman, AL 2017, 'Expression of p63 protein in anaplastic large cell lymphoma: implications for genetic subtyping', Human Pathology, vol. 64, pp. 19-27. https://doi.org/10.1016/j.humpath.2017.01.003
Wang, Xueju ; Boddicker, Rebecca L. ; Dasari, Surendra ; Sidhu, Jagmohan S. ; Kadin, Marshall E. ; Macon, William R. ; Ansell, Stephen M. ; Ketterling, Rhett P. ; Rech, Karen L. ; Feldman, Andrew L. / Expression of p63 protein in anaplastic large cell lymphoma : implications for genetic subtyping. In: Human Pathology. 2017 ; Vol. 64. pp. 19-27.
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abstract = "Anaplastic large cell lymphomas (ALCLs) are CD30-positive T-cell non-Hodgkin lymphomas that bear chromosomal rearrangements of the TP53 homologue TP63 in a subset of cases that demonstrate aggressive clinical behavior. In the present study, we examined the relationship between p63 protein expression by immunohistochemistry and the results of fluorescence in situ hybridization using TP63 probes in 116 ALCLs. We also determined the relative expression of full-length TAp63 and truncated ΔNp63 isoforms (eg, p40) in ALCL cell lines and a subset of clinical cases. Overall, 35.3{\%} of ALCLs were positive for p63 protein. Primary cutaneous and anaplastic lymphoma kinase–negative ALCLs were positive more frequently than anaplastic lymphoma kinase–positive ALCLs (P = .0034). As previously reported, cases with TP63 gene rearrangements expressed p63 uniformly. p63 expression in nonrearranged cases was associated with extra copies of TP63 on 3q28 (P < .0001). Extra copies of TP63 correlated with extra copies of the DUSP22 locus on 6p25.3 (P < .0001). Results of immunohistochemistry, Western blotting, and RNA sequencing indicated that p63 expression in nonrearranged cases was entirely attributable to TAp63 isoforms. Taken together, these findings indicate that ALCLs without TP63 rearrangements may express TAp63 isoforms of p63 and that this expression is associated with extra copies of TP63, probably due to widespread genomic copy number abnormalities rather than focal gains. Immunohistochemistry for p63 in ALCL is not specific for TP63 rearrangements but is useful clinically as a screening test to select cases for further testing by fluorescence in situ hybridization. Immunohistochemistry for ΔNp63 (p40) is not informative in the evaluation of ALCL.",
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T2 - implications for genetic subtyping

AU - Wang, Xueju

AU - Boddicker, Rebecca L.

AU - Dasari, Surendra

AU - Sidhu, Jagmohan S.

AU - Kadin, Marshall E.

AU - Macon, William R.

AU - Ansell, Stephen M.

AU - Ketterling, Rhett P.

AU - Rech, Karen L.

AU - Feldman, Andrew L.

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N2 - Anaplastic large cell lymphomas (ALCLs) are CD30-positive T-cell non-Hodgkin lymphomas that bear chromosomal rearrangements of the TP53 homologue TP63 in a subset of cases that demonstrate aggressive clinical behavior. In the present study, we examined the relationship between p63 protein expression by immunohistochemistry and the results of fluorescence in situ hybridization using TP63 probes in 116 ALCLs. We also determined the relative expression of full-length TAp63 and truncated ΔNp63 isoforms (eg, p40) in ALCL cell lines and a subset of clinical cases. Overall, 35.3% of ALCLs were positive for p63 protein. Primary cutaneous and anaplastic lymphoma kinase–negative ALCLs were positive more frequently than anaplastic lymphoma kinase–positive ALCLs (P = .0034). As previously reported, cases with TP63 gene rearrangements expressed p63 uniformly. p63 expression in nonrearranged cases was associated with extra copies of TP63 on 3q28 (P < .0001). Extra copies of TP63 correlated with extra copies of the DUSP22 locus on 6p25.3 (P < .0001). Results of immunohistochemistry, Western blotting, and RNA sequencing indicated that p63 expression in nonrearranged cases was entirely attributable to TAp63 isoforms. Taken together, these findings indicate that ALCLs without TP63 rearrangements may express TAp63 isoforms of p63 and that this expression is associated with extra copies of TP63, probably due to widespread genomic copy number abnormalities rather than focal gains. Immunohistochemistry for p63 in ALCL is not specific for TP63 rearrangements but is useful clinically as a screening test to select cases for further testing by fluorescence in situ hybridization. Immunohistochemistry for ΔNp63 (p40) is not informative in the evaluation of ALCL.

AB - Anaplastic large cell lymphomas (ALCLs) are CD30-positive T-cell non-Hodgkin lymphomas that bear chromosomal rearrangements of the TP53 homologue TP63 in a subset of cases that demonstrate aggressive clinical behavior. In the present study, we examined the relationship between p63 protein expression by immunohistochemistry and the results of fluorescence in situ hybridization using TP63 probes in 116 ALCLs. We also determined the relative expression of full-length TAp63 and truncated ΔNp63 isoforms (eg, p40) in ALCL cell lines and a subset of clinical cases. Overall, 35.3% of ALCLs were positive for p63 protein. Primary cutaneous and anaplastic lymphoma kinase–negative ALCLs were positive more frequently than anaplastic lymphoma kinase–positive ALCLs (P = .0034). As previously reported, cases with TP63 gene rearrangements expressed p63 uniformly. p63 expression in nonrearranged cases was associated with extra copies of TP63 on 3q28 (P < .0001). Extra copies of TP63 correlated with extra copies of the DUSP22 locus on 6p25.3 (P < .0001). Results of immunohistochemistry, Western blotting, and RNA sequencing indicated that p63 expression in nonrearranged cases was entirely attributable to TAp63 isoforms. Taken together, these findings indicate that ALCLs without TP63 rearrangements may express TAp63 isoforms of p63 and that this expression is associated with extra copies of TP63, probably due to widespread genomic copy number abnormalities rather than focal gains. Immunohistochemistry for p63 in ALCL is not specific for TP63 rearrangements but is useful clinically as a screening test to select cases for further testing by fluorescence in situ hybridization. Immunohistochemistry for ΔNp63 (p40) is not informative in the evaluation of ALCL.

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