Polysomy of chromosome 17 in breast cancer patients and its impact to diagnosis and treatment

Konference: 2009 5. sympózium a workshop molekulární patologie a histo-cyto-chemie

Kategorie: Nádorová biologie/imunologie/genetika a buněčná terapie

Téma: Postery

Číslo abstraktu: p010

Autoři: MUDr. Vladimíra Koudeláková (Palková); MUDr. Magdalena Čížková; RNDr. Radek Trojanec, Ph.D.; Mgr. Lenka Radová, Ph.D.; prof. MUDr. Bohuslav Melichar, Ph.D.; MUDr. Kateřina Bouchalová (Špačková), Ph.D.; Soňa Mlčochová; prof. MUDr. Zdeněk Kolář, CSc.; Mgr. Marta Dziechciarková, Ph.D.; doc. MUDr. Marián Hajdúch, Ph.D.

Amplification and/or overexpression of the Her-2/neu gene has been reported in approximately 20 % of patients with breast cancer. These changes are associated with poor prognosis and higher tumor aggressiveness. Humanized monoclonal antibody trastuzumab (Herceptin, Genentech; anti-p185Her2) was developed for treatment of breast cancer patients with ratio Her-2/neu: chromosome 17 (CH17) copy number > 2.2 and/or immunohistochemically positive 3+. Roughly 5-7 % of breast cancer patients are not indicated for trastuzumab therapy because they do not match Her-2/neu: CH17 criteria due to CH17 polysomy. The efficacy of trastuzumab in poly-somic cases has not yet been confirmed. Apart from Her-2/ neu, the most frequently altered genes in breast cancer are TOP2A (topoisomerase 2a), C-MYC and CCND1 (cyclin D1). We focused on the status of genes C-MYC and CCND1 and corresponding chromosomes 8 and 11 for two reasons:: amplification of C-MYC gene has been described as a positive predictor for 5-fluorouracil therapy in colon cancer (for breast cancer the comparable study has not been published yet) and amplification of CCND1 gene is considered to be a negative predictive marker for tamoxifen therapy in patients with early stagebreast cancer and positive hormonal receptors. These numerical changes can be prognostically important as well as useful in predictingof tailored therapy.

For the pilot study, we chose 280 patients: 112 (40 %) with confirmed chromosome 17 polysomy (CH17 copy number > 2.5) and 168 (60 %) with diploid status. Amplification of C-MYC, resp. CCND1 was determined in 48.2 % (54/112), resp. 47.3 % (53/112) cases with CH17 polysomy vs. 10.7 % (18/168), resp. 23.2 % (39/168) without CH17 polysomy. Extra copies of chromosome 8 and 11 > 2.5) were found in 34.8 % (39/112) and 23.2 % (26/112) cases with CH17 polysomy vs. 2.4 % (4/168) and 4.2 % (7/168) without CH17 polysomy.

Our data demonstrate more frequent genetic alterations in CH17 polysomic tumors. Their clinical relevance is being analyzed.

Acknowledgement: Project was supported in parts by grants MSM6198959216, LC07017 and GACR 303/09/H048. Special thanks belongs to all cooperating clinical departments and local laboratories.

Datum přednesení příspěvku: 24. 4. 2009