Tumor biomarkers in cervical cancer: focus on Ki-67 proliferation factor and E-cadherin expression

Despite recent advances in the immune mechanisms of cervical cancer (CC) and complex management opportunities, relapse remains still an actual issue. While predictive factors are required, current research is directed towards proliferation and tumor aggressiveness biomarkers as potential negative factors in CC. The main objectives were to assess tumor proliferation and invasiveness biomarkers (Ki-67, E-cadherin) and to identify potential correlation between biomarkers and classic prognostic factors in CC. Radical hysterectomy specimens from 61 consecutive CC were immunohistochemically investigated for Ki-67 and E-cadherin. Nuclear immunostaining for Ki-67 proliferation index was assigned scores 1 to 3, "+" meaning low (10-30%), "++" moderate (30-50%), "+++" high-proliferation rate (>50%); cell membrane E-cadherin staining was either negative or positive. Statistical analysis was performed in SPSS-13 software, p<0.05.

no significant correlation between Ki-67 and classical prognostic factors (p>0.05) was reported; however, in relapsed CC, Ki-67 correlates with tumor grading (r=0.386, p<0.05). Significant correlation between E-cadherin and tumor size (r=-0.280, p=0.029), relapse (r=-0.386, p=0.002) and disease free survival (r=0.374, p=0.003) were demonstrated. Indirect statistically significant moderate correlation between Ki-67 and E-cadherin (r=-0.461, p<0.00001) was shown, mainly in invasive squamous CC (r=-0.549, p=0.0001), stage IB (r=-0.578, p=0.009), IIB (r=-0.585, p=0.003), relapsed CC (r=-0.525, p<0.01), HPV-infection (r=-0.504, p=0.033).

CC aggressiveness, particularly in invasive squamous carcinoma, either 16 or 18 HPV-positive cases, FIGO stage IB and IIB, and cases with relapse, depends on two pivotal factors, tumor proliferation rate (Ki-67) and tumor invasiveness (E-cadherin).