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Evaluation of predictive and prognostic significance of serum TGF-beta1 levels in breast cancer according to HER-2 codon 655 polymorphism

In: NEOPLASMA, vol. 55, no. 3
E. Papadopoulou - K. Anagnostopoulos - G. Tripsianis - I. Tentes - S. Kakolyris - G. Galazios - E. Sivridis - K. Simopoulos - A. Kortsaris
Detaily:
Rok, strany: 2008, 229 - 238
O článku:
The present study was conducted to clarify the predictive and prognostic significance of serum TGF-β1 in breast cancer in relation to Ile655Val single nucleotide polymorphism (SNP) of human epidermal growth factor receptor-2 (HER-2). In a case-control study, 56 consecutive patients with primary breast cancer were prospectively included and evaluated. The control group consisted of 45 healthy women. Serum concentrations of TGF-β1 were measured by quantitative sandwich enzyme immunoassay (ELISA). HER-2 SNP was genotyped using PCR-RFLP method. Serum levels of TGF-β1 were significantly increased in breast cancer patients compared to healthy controls (p<0.001). For the evaluation of the diagnostic significance of serum TGF-β1 the area under the receiver operating characteristic (ROC) curve (AUC) was 0.804, while the optimal cut-off point of 30.86 ng/ml was determined to classify breast cancer patients, which yielded sensitivity of 77%, specificity of 78% and accuracy of 77%. Significantly elevated serum TGF-β1 levels were associated with advanced stages (p=0.023), positive lymph nodes (p=0.019) and postmenopausal status (p=0.031). A marginal trend towards higher TGF-β1 levels was found among patients with Val-containing genotypes compared to homozygous Ile-Ile (p=0.094). In multivariate analysis lymph node metastases (p=0.009) remained the only significant independent determinant of high TGF-β1 levels. With regard to prognostic significance for advanced stages (AUC, 0.704) and lymph node metastasis (AUC, 0.683), when the optimal cut-off value was set at 65.15 pg/ml, the sensitivity was 86% and 67%, the specificity was 60% and 62% and accuracy was 66% and 64%, respectively. Survival was shorter in patients with increased serum TGF-β1 (36 months vs 46 months, p=0.022). Multivariate analysis demonstrated a marginal prognostic significance of serum TGF-β1 for survival (p=0.072). The combination of high TGF-β1 and Val-Val genotype predicts a worse prognosis than high serum TGF-β1 alone. Our findings suggest that serum TGF-β1 is involved in tumor malignancy and lymph node metastasis and could be used clinically as a useful tumor marker for evaluation, the extension and the outcome of the disease. They also provide clinical evidence for a significant association between HER-2 Ile655Val SNP and serum TGF-β1, resulting to more aggressive phenotype of the tumor and poor prognosis. Key words: serum TGF-beta1, HER-2, polymorphism, breast cancer, survival
Ako citovať:
ISO 690:
Papadopoulou, E., Anagnostopoulos, K., Tripsianis, G., Tentes, I., Kakolyris, S., Galazios, G., Sivridis, E., Simopoulos, K., Kortsaris, A. 2008. Evaluation of predictive and prognostic significance of serum TGF-beta1 levels in breast cancer according to HER-2 codon 655 polymorphism. In NEOPLASMA, vol. 55, no.3, pp. 229-238. 0028-2685.

APA:
Papadopoulou, E., Anagnostopoulos, K., Tripsianis, G., Tentes, I., Kakolyris, S., Galazios, G., Sivridis, E., Simopoulos, K., Kortsaris, A. (2008). Evaluation of predictive and prognostic significance of serum TGF-beta1 levels in breast cancer according to HER-2 codon 655 polymorphism. NEOPLASMA, 55(3), 229-238. 0028-2685.