Significance of serum tumor necrosis factor-alpha and its combination with HER-2 codon 655 polymorphism in the diagnosis and prognosis of breast cancer.

Abstract

PURPOSE:

The present study was conducted to clarify the diagnostic and prognostic significance of TNF-alpha and its combination with HER-2 Ile655Val SNP in breast cancer.

METHODS:

In this case-control study, 56 consecutive patients with primary breast cancer were prospectively evaluated. The control group consisted of 45 healthy women. Serum concentrations of TNF-alpha were measured by quantitative sandwich enzyme immunoassay (ELISA). HER-2 SNP was genotyped using the PCR-RFLP method.

RESULTS:

Serum TNF-alpha was significantly increased in patients compared to controls. ROC analysis indicated a cutoff point of 11.00 pg/mL to classify breast cancer patients (sensitivity, 86%; specificity, 71%). Elevated TNF-alpha levels were associated with larger, poorly differentiated, invasive and advanced-stage tumors, and >3 positive lymph nodes. Regarding HER-2 SNP, patients with Ile-Val and Val-Val genotypes had significant TNF-alpha elevation compared with homozygous Ile-Ile patients. In multivariate analysis, high serum TNF-alpha remained an independent prognostic factor of worse overall survival; its combination with Val-Val genotype predicted a worse prognosis than high TNF-alpha alone.

CONCLUSIONS:

Serum TNF-a could be used clinically as a useful tumor marker for diagnosis, disease extent and outcome of breast cancer. The negative impact on survival seems to be enhanced through the interaction with HER-2 Ile655Val SNP.

• Authors: Evropi Papadopoulou, Gregory Tripsianis, Konstantinos Anagnostopoulos, Ioannis Tentes, Stylianos Kakolyris, Georgios Galazios, Efthimios Sivridis, Konstantinos Simopoulos, Alexandros Kortsaris
• Journal: The International journal of biological markers (Int J Biol Markers) 2010 Jul-Sep Vol. 25 Issue 3 Pg. 126-35 ISSN: 1724-6008 [Electronic] United States
• PMID: 20872355 (Publication Type: Comparative Study, Journal Article)

Chemical References

• Biomarkers, Tumor
• Codon
• Tumor Necrosis Factor-alpha

Topics

• Adult
• Aged
• Aged, 80 and over
• Biomarkers, Tumor (blood, genetics)
• Breast Neoplasms (blood, diagnosis, epidemiology, genetics)
• Carcinoma (blood, diagnosis, epidemiology, genetics)
• Case-Control Studies
• Cell Differentiation
• Codon (genetics)
• Ethnicity (statistics & numerical data)
• Female
• Genes, erbB-2
• Genotype
• Humans
• Kaplan-Meier Estimate
• Middle Aged
• Neoplasm Invasiveness
• Polymorphism, Single Nucleotide
• Prognosis
• Prospective Studies
• Sensitivity and Specificity
• Tumor Necrosis Factor-alpha (analysis)