Naslov
Detection of Clonal T-Cell Receptor (TCR) Gene Recombinations in Suspected Lymphoproliferations

Autori
Kardum Paro, Mirjana Mariana ; Šiftar, Zoran ; Flegar-Meštrić Zlata ; Kardum-Skelin, Ika ; Jelić Puškarić, Biljana ; Gašparov, Slavko ; Ostojić Kolonić, Slobodanka.

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, stručni

Izvornik
Cytopathology Volume 23 Supplement 1 / Herbert, A ; Cochand-Priollet, B - Oxford : Wiley-Blackwell, 2012, 55-55

Skup
37th European Congress of Cytology

Mjesto i datum
Cavtat, Hrvatska; Dubrovnik, Hrvatska, 30.09.2012. - 03.10.2012

Vrsta sudjelovanja
Pozvano predavanje

Vrsta recenzije
Međunarodna recenzija

Ključne riječi
TCR; gene recombinations; lymphoproliferations

Sažetak
In most cases with suspected T cell proliferations (T- CP), cytomorphology and histomorphology can discriminate between malignant and reactive T- CP. In minority of cases (5–10%) making the diagnosis of T- CP is more complicated. It is often supported by use of the polymerase chain reaction (PCR) to detect gene rearrangements of the T- cell receptors c and b (TCRc and TCRb) which provide information of practical diagnostic value and is an important tool for the assessment of TCR gene clonality. Naimely, functionally rearranged TCR genes result in surface membrane expression of TCRab or TCRcd molecules. Therefore both TCR genes (TCRc and TCRb) should be analysed in parallel. Based on the concept that only a single type of TCR molecule is expressed by a T- lymphocyte clone, the clonally rearranged TCR genes might be detected at protein level with many different antibodies against variable regions of the various TCR chains (b, c or d). The detection of TCRc and TCRb gene rearrangements is not indicative of T cells of the ab or cd T-cell lineage. The principle of the TCRc and TCRb gene rearrangements using the PCR is that consensus primers binding to various regions of the TCR genes are used, that amplification does not proceed unless the TCR genes are rearranged, that the length of amplified genes varies depending on the number of nucleotides removed and that length homogeneity or heterogeneity of the amplified material can be detected by electrophoresis enabling the distinctionof monoclonality from polyclonality. Although highly informative and of practical diagnostic value, molecular clonality assessed by PCR has several limitations which could affect on the interpretation of the results: the detection limit varies between 1% and 10% dependent on the applied technique, TCR gene rearrangements are not markers for lineage and clonality is not equivalent to malignancy. False-negative results obtained by PCR are usually due to improper annealing of primers to the rearranged gene regions, while false-positive PCR results obtained by PCR could be due to difficult discrimination between monoclonal and polyclonal TCR gene rearrangements. Therefore in a European BIOMED-2 collaborative study multiplex PCR assays have successfully been developed and standardized for the detection of clonally rearranged immunoglobulin (Ig) and TCR genes. Today PCR based clonality testing in T- CP has matured into a reliable method easily used in every laboratory with routine molecular diagnostics, but the results of molecular clonality studies should always be interpreted in the context of the clinical, morphological and immunophenotypic diagnosis.

Izvorni jezik
Engleski

Znanstvena područja
Temeljne medicinske znanosti, Kliničke medicinske znanosti

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