Expression of CK7 and CDKN2 in Cervical Intraepithelial Neoplasia and Correlation with Clinical Outcome.

AIM: To evaluate cyclin-dependent kinase inhibitor 2A (CDKN2A) and cytokeratin 7 (CK7) expression in cervical intraepithelial neoplasia (CIN) formalin-fixed samples. MATERIALS AND METHODS: Staining with antibody clones G175-405 for CDKN2A and OV-TL 12/30 for CK7 were evaluated and the detection of protein expressions were compared in 147 patients with CIN. RESULTS: Clinical follow-up of patients with CIN1 and CIN2 showed that most patients had a favorable outcome. Single CDKN2A or CK7 expression and their combined expression had a greater sensitivity and negative predictive value in CIN1, corresponding to the non-development of the disease. The positive predictive value of CDKN2A was greater than that of CK7. Combined expression of CDKN2A and CK7 showed that the sensitivity, specificity, positive predictive values, and negative predictive values had their maximum index in the CIN1 group. Analysis of combined expression of CDKN2A and CK7 showed that 85.7% of patients presented unfavorable clinical outcomes, with positive expression for both markers identified in CIN2. CONCLUSION: Combined expression of CK7 and CDKN2A was associated with a better diagnosis of CIN, and negative expression in CIN1/2 groups had a greater negative predictive value for patient clinical outcome.

Immunohistochemical Expression of VEGF and Podoplanin in Uterine Cervical Squamous Intraepithelial Lesions.

VEGF and podoplanin (PDPN) have been identified as angiogenesis and/or lymphangiogenesis regulators and might be essential to restrict tumor growth, progression, and metastasis. In the present study, we evaluate the association between the expression of these markers and CIN grade. Immunohistochemistry was performed in 234 uterine cervical samples using conventional histologic sections or TMA with the monoclonal antibodies to VEGF (C-1 clone) and podoplanin (D2-40 clone). Positive-staining rates of VEGF in 191 CIN specimens were significantly associated with histological grade (P < 0.001). Negative and/or focal immunostaining for PDPN were more frequent in CIN 3 (P = 0.016). We found that patients with CIN 3 more frequently had strong and more diffuse staining for VEGF and diminished staining for PDPN (P = 0.018). Strong and more diffuse VEGF immunoexpressions in CIN 2 and CIN 3 were detected when compared to CIN 1. Negative and/or focal PDPN immunoexpression appear to be more frequent in CIN 3. Moderate to strong VEGF expression may be a tendency among patients with high-grade lesions and diminished PDPN expression.