Abstract:

Objective

To investigate the expression of Ki67 and proliferating cell nuclear antigen(PCNA) in three different subtypes of breast cancer and their clinical significance.

Methods

Immunohistochemistry was used to detect the expression of Ki67 and PCNA in tissue samples from 251 breast cancer patients. kruskal-wallis rank sum test was used to analyze the expression difference of Ki67 and PCNA in different subtypes, Spearman rank test for the correlation of their expressions, and the correlation with primary tumor diameter, axillary lymph node metastasis and pathological classification, respectively. Meanwhile, the survival analysis was conducted to display the prognostic value of Ki67 and PCNA expression.

Results

The expressions of Ki67 and PCNA were not significantly different among the three subtypes of breast cancer(luminal,HER-2 and triple negative) (χ² =3.722,P=0.155;χ² =5.135,P=0.077). There was a positive correlation between Ki67 and PCNA expressions in general(r_s=0.348,P＜0.001)and in luminal subtype(r_s=0.467, P＜0.001), but no correlation was observed in other subtypes(P＞0.05). In luminal subtype, the expression of Ki67 was positively correlated with primary tumor diameter, axillary lymph node status and histological grade (r_s=0.180,P=0.017;r_s=0.236,P=0.002;r_s=0.156,P=0.039, respectively), and no correlation was showed in HER-2 and triple-negative subtypes(P ＞0.05). We also observed the positive correlation between PCNA expression and axillary lymph node status in luminal subtype, a negative correlation with primary tumor diameter in HER-2 subtype (r_s = -0.342, P=0.020), but no correlations with other pathological factors were found (P ＞0.05). Univariate analysis showed axillary lymph node metastasis and nuclear grade had influence on tumor-free survival of breast cancer patients (HR=4.431, 95%CI: 1.787 to 10.984; HR= 2.492, 95% CI: 1.032 to 6.018). The subgroup analysis displayed axillary lymph node metastasis and PCNA had effects on tumor-free survival in luminal subtype (HR=3.930, 95%CI: 1.343 to 11.501; HR=2.401, 95% CI: 1.044 to 5.524). Multivariate COX analysis showed axillary lymph node metastasis was an independent prognostic factor in general and luminal subtype breast cancer patients (HR=3.780,95%CI:1.461 to 9.775; HR=3.403,95%CI:1.150 to 10.075).

Conclusion

Ki67 and PCNA can indicate the poor prognosis of luminal subtype breast cancer patients to a certain extent, but have no influence on HER-2 and triple negative subtypes.

Key words: breast neoplasms, immunohistochemistry, Ki67, proliferating cell nuclear antigen