Expression of p63 protein in anaplastic large cell lymphoma: implications for genetic subtyping.
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.
Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN 55905; Department of Pathology, The China-Japan Union Hospital of Jilin University, Changchun, Jilin Province 130033, China.
Xueju
X
Wang
Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN 55905.
Rebecca L
RL
Boddicker
Department of Health Sciences Research, Mayo Clinic, Rochester, MN 55905.
Surendra
S
Dasari
Department of Pathology and Laboratory Medicine, United Health Services Hospitals, Johnson City/Binghamton, NY 13790.
Jagmohan S
JS
Sidhu
Department of Dermatology, Roger Williams Medical Center, Providence, RI 02908.
Marshall E
ME
Kadin
Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN 55905.
William R
WR
Macon
Division of Hematology, Mayo Clinic, Rochester, MN 55905.
Stephen M
SM
Ansell
Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN 55905.
Rhett P
RP
Ketterling
Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN 55905.
Karen L
KL
Rech
Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN 55905. Electronic address: feldman.andrew@mayo.edu.
Andrew L
AL
Feldman
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000077548:Anaplastic Lymphoma Kinase; D014408:Biomarkers, Tumor / Q000032:analysis* / Q000235:genetics; D001706:Biopsy; D002648:Child; D056915:DNA Copy Number Variations; D005260:Female; D005784:Gene Amplification; D018628:Gene Dosage; D015321:Gene Rearrangement; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D017728:Lymphoma, Large-Cell, Anaplastic / Q000737:chemistry* / Q000235:genetics / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D020033:Protein Isoforms; D020794:Receptor Protein-Tyrosine Kinases / Q000032:analysis; D014157:Transcription Factors / Q000032:analysis* / Q000235:genetics; D025521:Tumor Suppressor Proteins / Q000032:analysis* / Q000235:genetics; D055815:Young Adult
D014408:Biomarkers, Tumor; D020033:Protein Isoforms; C115051:TP63 protein, human; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; C000626173:ALK protein, human; D000077548:Anaplastic Lymphoma Kinase; D020794:Receptor Protein-Tyrosine Kinases
Anaplastic large cell lymphoma; Copy number abnormality; Fluorescence in situ hybridization; TP63; p40; p63