Konference: 2010 6. sympózium a workshop molekulární patologie a histo-cyto-chemie
Kategorie: Nádorová biologie/imunologie/genetika a buněčná terapie
Téma: Postery
Číslo abstraktu: p002
Autoři: MUDr. Kateřina Bouchalová (Špačková), Ph.D.; MUDr. Magdalena Čížková; RNDr. Radek Trojanec, Ph.D.; Soňa Mlčochová; ]. Furstová; Mgr. Lenka Radová, Ph.D.; Mgr. Marta Dziechciarková, Ph.D.; prof. MUDr. Bohuslav Melichar, Ph.D.; MUDr. Karel Cwiertka, Ph.D.; prof. MUDr. Zdeněk Kolář, CSc.; doc. MUDr. Marián Hajdúch, Ph.D.
Introduction and Aim: ´Triple negative´
breast cancer (TNBC), oestrogen (ER), progesterone (PR) and HER2
receptor negative is an aggressive form of breast cancer (BC) with
poor prognosis. Further, TNBC patients cannot benefit from
treatment based on ER, PR and HER2. Other markers are sought. TOP2A
gene amplification is considered an anthracycline treatment
response predictor and TOP2A aberrations (amplifications,
deletions) are found in HER2 amplified BC. Recently,TOP2A
amplification has been described in HER2 non-amplified BC. We
investigated this further.
Materials and methods: Retrospective tumor samples from 68 TNBC patients diagnosed with clinical stage I and II were assessed by fluorescent in situ hybridization (FISH). The TOP2A/ chromosome 17 ratio was counted. Histopathological and clinical data were analyzed with the cytogenetic results using standard statistical methods.
Results: TOP2A gene amplification was found in 10.3% of cases. Rare deletion was detected in 4.4%. TOP2A gene changes were found only in tumors with HER1 non-amplified status. Anthracycline therapy was used in 18 patients. The 2 anthracycline-treated patients displaying TOP2A amplification are alive and disease-free.
Statistical analysis showed association between patient age at diagnosis and histopathological diagnosis (p=0.0165). Tumors with normal TOP2A FISH findings had higher bcl-2 expression (p=0.0364). Associations between TOP2A and HER2 gene copy numbers (p<0.00001) and between TOP2A gene copy number and HER2/chromosome 17 centromere ratio (p=0.0183) were also found.
Conclusion: TOP2A amplification, a predictive factor for anthracycline therapy response, is usually connected to HER2 amplification. Here we present TOP2A gene changes in HER2 non-amplified tumors, a result which supports some previously published data. These findings suggest the possibility of targeted treatment with anthracyclines in TNBC. Association between TOP2A and HER2 gene copy numbers, even in the absence of HER2 amplification as in TNBC, confirms a relationship of both genes in the process of cytogenetic changes. The clinical application of the rare 4.4% TOP2A deletion found, however is unclear.
Supported by grants: IGA NS10286-3, MSM 6198959216, LC07017 a EEA/Norway Financial Mechanisms(CZ0099).
Materials and methods: Retrospective tumor samples from 68 TNBC patients diagnosed with clinical stage I and II were assessed by fluorescent in situ hybridization (FISH). The TOP2A/ chromosome 17 ratio was counted. Histopathological and clinical data were analyzed with the cytogenetic results using standard statistical methods.
Results: TOP2A gene amplification was found in 10.3% of cases. Rare deletion was detected in 4.4%. TOP2A gene changes were found only in tumors with HER1 non-amplified status. Anthracycline therapy was used in 18 patients. The 2 anthracycline-treated patients displaying TOP2A amplification are alive and disease-free.
Statistical analysis showed association between patient age at diagnosis and histopathological diagnosis (p=0.0165). Tumors with normal TOP2A FISH findings had higher bcl-2 expression (p=0.0364). Associations between TOP2A and HER2 gene copy numbers (p<0.00001) and between TOP2A gene copy number and HER2/chromosome 17 centromere ratio (p=0.0183) were also found.
Conclusion: TOP2A amplification, a predictive factor for anthracycline therapy response, is usually connected to HER2 amplification. Here we present TOP2A gene changes in HER2 non-amplified tumors, a result which supports some previously published data. These findings suggest the possibility of targeted treatment with anthracyclines in TNBC. Association between TOP2A and HER2 gene copy numbers, even in the absence of HER2 amplification as in TNBC, confirms a relationship of both genes in the process of cytogenetic changes. The clinical application of the rare 4.4% TOP2A deletion found, however is unclear.
Supported by grants: IGA NS10286-3, MSM 6198959216, LC07017 a EEA/Norway Financial Mechanisms(CZ0099).
Datum přednesení příspěvku: 23. 4. 2010
