Neuronal apoptosis inhibitory protein is overexpressed in patients with unfavorable prognostic factors in breast cancer

Abstract

Neuronal apoptosis inhibitory protein (NAIP) is a recently identified inhibitor of apoptosis protein. However, the clinical relevance of NAIP expression is not completely understood. In an attempt to determine the clinical relevance of NAIP expression in breast cancer, the levels of NAIP and survivin expression were measured in 117 breast cancer samples and 10 normal breast tissues using quantitative reversetranscriptase-polymerase chain reaction. While there was no evidence of NAIP expression in the normal breast tissue, NAIP was expressed in all breast cancer samples. The level of NAIP expression in breast cancer was significantly higher (257 times) than in the universal tumor control. There was a strong correlation between the level of NAIP expression and the level of survivin expression (p=0.001). The level of NAIP expression in patients with a large tumor (>/=T2) and patients with an unfavorable histology (nuclear grade III) was significantly higher than in those patients with a small tumor (T1) and patients with a favorable histology (nuclear grade I, II) (p=0.026 and p=0.050, respectively). Although the level of NAIP expression was higher in patients with other unfavorable prognostic factors, it was not significant. The three-year relapse-free survival rate was not significantly the patients showing high NAIP expression and patients showing low NAIP expression (86.47plusmn;4.79% vs. 78.74plusmn;6.57%). Further studies should include the expressions of NAIP in a larger number of patients and for a longer period of follow-up to evaluate correlation with metastasis and treatment outcome. In conclusion, NAIP is overexpressed in breast cancer patients with unfavorable clinical features such as stage and tumor size, suggesting that NAIP would play a role in the disease manifestation.

Fig. 1

Relative expression levels of NAIP and survivin mRNA compared with universal human reference RNA. The level of NAIP expression was 257 times higher than the control, whereas the median level of survivin expression was 0.8 times that of the control (A). The correlations between NAIP and survivin expression in each patient were analyzed by a Spearman's rank correlation test. Positive correlation was observed between NAIP and survivin (B, p=0.0001).

Fig. 2

Levels of NAIP expression according to clinicopathologic prognostic factors. NAIP overexpression was correlated with the presence of unfavorable prognostic factors, T2 (A) and nuclear grade III (B).

Fig. 3

Expression of NAIP was slightly higher in relapsed patients than in relapse-free patients (266 vs. 202 folds of control, p=0.608). (A) The relapse-free survival rate also was slightly higher in patients with a high level of NAIP expression (86.47±4.79%) than in patients with a low level of NAIP expression (78.74±6.57%) (B). This three-year relapse-free survival according to NAIP expression did not show a statistical significance (p=0.511).