title: In situ detection of hTERT variants in anaplastic large cell lymphoma.
abstract: The expression of hTERT and its isoforms is difficult to assess in lymphoma tissues with the commonly used reverse transcription-polymerase chain reaction (RT-PCR) methods, because non-neoplastic lymphocytes expressing hTERT are always present in the lymphomatous infiltrates. The present study aimed to investigate hTERT mRNA variants in anaplastic large cell lymphoma (ALCL) (n = 38) with in situ hybridization (ISH), along with the immunodetection of hTERT protein. Probes for the identification of mRNAs containing (Bplus) and lacking (Bdel) exons 7 and 8 of the hTERT mRNA were used. Normal lymphocyte populations equally expressed both Bplus and Bdel mRNAs. Although all ALCL examined were found positive for hTERT expression with RT-PCR, hTERT mRNAs were identified in 68% of these tumors with ISH, with a higher incidence in the group bearing ALK translocations (10 out of 11; 90.9%) compared to the ALK negative group (17 out of 27; 59.3%) (PPearson's = 0.002). The same results were obtained with immunohistochemistry for hTERT. In approximately 50% of cases, only Bplus positive cells were identified, again with a higher incidence in the ALK positive compared to the ALK negative group (PPearson's = 0.016). In conclusion, ISH for hTERT mRNAs appears to be a valuable tool for the investigation of hTERT expression in lymphomas. Aberrations in hTERT variant profiles and a decline in the expression of the B deleted isoform may be associated with the pathogenesis of ALCL, especially with respect to ALK positive tumors.
authors.affiliation: Department of Pathology, School of Medicine, Aristotle University, Thessaloniki, Greece.
authors.forename: Vassiliki
authors.initials: V
authors.lastname: Kotoula
authors.forename: Mattheos
authors.initials: M
authors.lastname: Bobos
authors.forename: Ioannis
authors.initials: I
authors.lastname: Kostopoulos
authors.forename: Vassiliki
authors.initials: V
authors.lastname: Kaloutsi
authors.forename: Triantafyllia
authors.initials: T
authors.lastname: Koletsa
authors.forename: Georgia
authors.initials: G
authors.lastname: Karayannopoulou
authors.forename: Constantine S
authors.initials: CS
authors.lastname: Papadimitriou
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D005260:Female; D014644:Genetic Variation; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization / Q000379:methods* / Q000592:standards; D008214:Lymphocytes / Q000378:metabolism; D017728:Lymphoma, Large-Cell, Anaplastic / Q000175:diagnosis / Q000201:enzymology / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics; D019098:Telomerase / Q000235:genetics*
chemical_list: D009363:Neoplasm Proteins; D012333:RNA, Messenger; C509186:TERT protein, human; D019098:Telomerase