Significance of serum tumor necrosis factor-alpha and its combination with HER-2 codon 655 polymorphism in the diagnosis and prognosis of breast cancer.
OBJECTIVE
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.
Papadopoulou
Evropi
E
Laboratory of Biochemistry, Medical School, Democritus University of Thrace, Alexandroupolis, Greece.
Tripsianis
Gregory
G
Anagnostopoulos
Konstantinos
K
Tentes
Ioannis
I
Kakolyris
Stylianos
S
Galazios
Georgios
G
Sivridis
Efthimios
E
Simopoulos
Konstantinos
K
Kortsaris
Alexandros
A
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000097:blood* / Q000235:genetics; D001943:Breast Neoplasms / Q000097:blood / Q000175:diagnosis* / Q000453:epidemiology / Q000235:genetics; D002277:Carcinoma / Q000097:blood / Q000175:diagnosis* / Q000453:epidemiology / Q000235:genetics; D016022:Case-Control Studies; D002454:Cell Differentiation; D003062:Codon / Q000235:genetics; D005006:Ethnicity / Q000706:statistics & numerical data; D005260:Female; D018734:Genes, erbB-2; D005838:Genotype; D006801:Humans; D053208:Kaplan-Meier Estimate; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D011446:Prospective Studies; D012680:Sensitivity and Specificity; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis*
D014408:Biomarkers, Tumor; D003062:Codon; D014409:Tumor Necrosis Factor-alpha