The impact of PTEN tumor suppressor gene on acquiring resistance to tamoxifen treatment in breast cancer patients
2012
Authors
Tanić, NikolaMilovanović, Zorka M.
Tanić, Nasta
Džodić, Radan R.
Juranic, Zorica
Šušnjar, Snežana
Plesinac-Karapandzic, Vesna
Tatic, Svetislav
Dramićanin, Tatjana
Davidović, Radoslav S.
Dimitrijević, Bogomir B.
Article (Published version)
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Tamoxifen is a standard therapeutical treatment in patients with estrogen receptor positive breast carcinoma. However, less than 50% of estrogen receptor positive breast cancers do not respond to tamoxifen treatment whereas 40% of tumors that initially respond to treatment develop resistance over time. The underlying mechanisms for tamoxifen resistance are probably multifactorial but remain largely unknown. The primary aim of this study was to investigate the impact of PTEN tumor suppressor gene on acquiring resistance to tamoxifen by analyzing loss of heterozygosity (LOH) and immunohystochemical expression of PTEN in 49 primary breast carcinomas of patients treated with tamoxifen as the only adjuvant therapy. The effect of PTEN inactivation on breast cancer progression and disease outcome was also analyzed. Reduced or completely lost PTEN expression was observed in 55.1% of samples, while 63.3% of samples displayed LOH of PTEN gene. Inactivation of PTEN immunoexpression significantly ...correlated with the PTEN loss of heterozygosity, suggesting LOH as the most important genetic mechanism for the reduction or complete loss of PTEN expression in primary breast carcinoma. Most importantly, LOH of PTEN and consequential reduction of its immunoexpression showed significant correlation with the recurrence of the disease. Besides, our study revealed that LOH of PTEN tumor suppressor was significantly associated with shorter disease free survival, breast cancer specific survival and overall survival. In summary, our results imply that LOH of PTEN could be used as a good prognostic characteristic for the outcome of breast cancer patients treated with tamoxifen.
Keywords:
breast cancer / tamoxifen / acquired resistance / endocrine treatment / loss of heterozygosity (LOH) / immunoexpression / PTENSource:
Cancer Biology and Therapy, 2012, 13, 12, 1165-1174Funding / projects:
- Identification of predictive molecular markers for cancer progression, response to therapy and disease outcome (RS-MESTD-Integrated and Interdisciplinary Research (IIR or III)-41031)
- Molecular determinants for tumor marker design (RS-MESTD-Basic Research (BR or ON)-173049)
DOI: 10.4161/cbt.21346
ISSN: 1538-4047
PubMed: 22892847
WoS: 000309559700005
Scopus: 2-s2.0-84867137307
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VinčaTY - JOUR AU - Tanić, Nikola AU - Milovanović, Zorka M. AU - Tanić, Nasta AU - Džodić, Radan R. AU - Juranic, Zorica AU - Šušnjar, Snežana AU - Plesinac-Karapandzic, Vesna AU - Tatic, Svetislav AU - Dramićanin, Tatjana AU - Davidović, Radoslav S. AU - Dimitrijević, Bogomir B. PY - 2012 UR - https://vinar.vin.bg.ac.rs/handle/123456789/5073 AB - Tamoxifen is a standard therapeutical treatment in patients with estrogen receptor positive breast carcinoma. However, less than 50% of estrogen receptor positive breast cancers do not respond to tamoxifen treatment whereas 40% of tumors that initially respond to treatment develop resistance over time. The underlying mechanisms for tamoxifen resistance are probably multifactorial but remain largely unknown. The primary aim of this study was to investigate the impact of PTEN tumor suppressor gene on acquiring resistance to tamoxifen by analyzing loss of heterozygosity (LOH) and immunohystochemical expression of PTEN in 49 primary breast carcinomas of patients treated with tamoxifen as the only adjuvant therapy. The effect of PTEN inactivation on breast cancer progression and disease outcome was also analyzed. Reduced or completely lost PTEN expression was observed in 55.1% of samples, while 63.3% of samples displayed LOH of PTEN gene. Inactivation of PTEN immunoexpression significantly correlated with the PTEN loss of heterozygosity, suggesting LOH as the most important genetic mechanism for the reduction or complete loss of PTEN expression in primary breast carcinoma. Most importantly, LOH of PTEN and consequential reduction of its immunoexpression showed significant correlation with the recurrence of the disease. Besides, our study revealed that LOH of PTEN tumor suppressor was significantly associated with shorter disease free survival, breast cancer specific survival and overall survival. In summary, our results imply that LOH of PTEN could be used as a good prognostic characteristic for the outcome of breast cancer patients treated with tamoxifen. T2 - Cancer Biology and Therapy T1 - The impact of PTEN tumor suppressor gene on acquiring resistance to tamoxifen treatment in breast cancer patients VL - 13 IS - 12 SP - 1165 EP - 1174 DO - 10.4161/cbt.21346 ER -
@article{ author = "Tanić, Nikola and Milovanović, Zorka M. and Tanić, Nasta and Džodić, Radan R. and Juranic, Zorica and Šušnjar, Snežana and Plesinac-Karapandzic, Vesna and Tatic, Svetislav and Dramićanin, Tatjana and Davidović, Radoslav S. and Dimitrijević, Bogomir B.", year = "2012", abstract = "Tamoxifen is a standard therapeutical treatment in patients with estrogen receptor positive breast carcinoma. However, less than 50% of estrogen receptor positive breast cancers do not respond to tamoxifen treatment whereas 40% of tumors that initially respond to treatment develop resistance over time. The underlying mechanisms for tamoxifen resistance are probably multifactorial but remain largely unknown. The primary aim of this study was to investigate the impact of PTEN tumor suppressor gene on acquiring resistance to tamoxifen by analyzing loss of heterozygosity (LOH) and immunohystochemical expression of PTEN in 49 primary breast carcinomas of patients treated with tamoxifen as the only adjuvant therapy. The effect of PTEN inactivation on breast cancer progression and disease outcome was also analyzed. Reduced or completely lost PTEN expression was observed in 55.1% of samples, while 63.3% of samples displayed LOH of PTEN gene. Inactivation of PTEN immunoexpression significantly correlated with the PTEN loss of heterozygosity, suggesting LOH as the most important genetic mechanism for the reduction or complete loss of PTEN expression in primary breast carcinoma. Most importantly, LOH of PTEN and consequential reduction of its immunoexpression showed significant correlation with the recurrence of the disease. Besides, our study revealed that LOH of PTEN tumor suppressor was significantly associated with shorter disease free survival, breast cancer specific survival and overall survival. In summary, our results imply that LOH of PTEN could be used as a good prognostic characteristic for the outcome of breast cancer patients treated with tamoxifen.", journal = "Cancer Biology and Therapy", title = "The impact of PTEN tumor suppressor gene on acquiring resistance to tamoxifen treatment in breast cancer patients", volume = "13", number = "12", pages = "1165-1174", doi = "10.4161/cbt.21346" }
Tanić, N., Milovanović, Z. M., Tanić, N., Džodić, R. R., Juranic, Z., Šušnjar, S., Plesinac-Karapandzic, V., Tatic, S., Dramićanin, T., Davidović, R. S.,& Dimitrijević, B. B.. (2012). The impact of PTEN tumor suppressor gene on acquiring resistance to tamoxifen treatment in breast cancer patients. in Cancer Biology and Therapy, 13(12), 1165-1174. https://doi.org/10.4161/cbt.21346
Tanić N, Milovanović ZM, Tanić N, Džodić RR, Juranic Z, Šušnjar S, Plesinac-Karapandzic V, Tatic S, Dramićanin T, Davidović RS, Dimitrijević BB. The impact of PTEN tumor suppressor gene on acquiring resistance to tamoxifen treatment in breast cancer patients. in Cancer Biology and Therapy. 2012;13(12):1165-1174. doi:10.4161/cbt.21346 .
Tanić, Nikola, Milovanović, Zorka M., Tanić, Nasta, Džodić, Radan R., Juranic, Zorica, Šušnjar, Snežana, Plesinac-Karapandzic, Vesna, Tatic, Svetislav, Dramićanin, Tatjana, Davidović, Radoslav S., Dimitrijević, Bogomir B., "The impact of PTEN tumor suppressor gene on acquiring resistance to tamoxifen treatment in breast cancer patients" in Cancer Biology and Therapy, 13, no. 12 (2012):1165-1174, https://doi.org/10.4161/cbt.21346 . .