Expression of TP73L is a helpful diagnostic marker of primary mediastinal large B-cell lymphomas.
Primary mediastinal large B-cell lymphoma is a well-defined lymphoma entity whose molecular pathogenesis is incompletely understood and also lacking well-established diagnostic markers. Recently, the presence of overlapping features between classical Hodgkin's lymphoma and primary mediastinal large B-cell lymphoma was highlighted by gene expression profiling as well as morphological studies. We investigated the expression of TP73L (commonly known as p63) isoforms in primary mediastinal large B-cell lymphoma at both protein and mRNA level, and demonstrated the exclusive presence of transactivating (TA) isoforms in all cases. We also demonstrated that TP73L is expressed in a subset of germinal center B-cells, as well as in some diffuse large B-cell lymphomas, but it is never present in classical Hodgkin lymphoma. Nodular lymphocyte predominant Hodgkin's lymphoma also showed TP73L positivity by immunohistochemistry. Isoform analysis by real-time PCR showed that TA-TP73Lalpha is the most represented in primary mediastinal large B-cell lymphoma, but TA-TP73Lgamma is the most differentially expressed in comparison to both germinal center B-cells and diffuse large B-cell lymphomas. TP73L expression proved a useful diagnostic marker of primary mediastinal large B-cell lymphoma, and gave new insights in to the molecular pathways playing a role in this lymphoma.
Zamò
Alberto
A
Department of Pathology, University of Verona, Verona, Italy.
Malpeli
Giorgio
G
Scarpa
Aldo
A
Doglioni
Claudio
C
Chilosi
Marco
M
Menestrina
Fabio
F
D014408:Biomarkers, Tumor / Q000032:analysis; D004268:DNA-Binding Proteins; D003937:Diagnosis, Differential; D015870:Gene Expression; D020869:Gene Expression Profiling; D016147:Genes, Tumor Suppressor; D006689:Hodgkin Disease / Q000175:diagnosis* / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D016393:Lymphoma, B-Cell / Q000175:diagnosis* / Q000378:metabolism; D016403:Lymphoma, Large B-Cell, Diffuse / Q000175:diagnosis* / Q000378:metabolism; D008479:Mediastinal Neoplasms / Q000175:diagnosis* / Q000378:metabolism; D010750:Phosphoproteins / Q000096:biosynthesis*; D020033:Protein Isoforms / Q000096:biosynthesis; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015534:Trans-Activators / Q000096:biosynthesis*; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins
D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; D010750:Phosphoproteins; D020033:Protein Isoforms; D012333:RNA, Messenger; C115051:TP63 protein, human; D015534:Trans-Activators; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins