Evaluation of p16INk4a, pRb, p53 and Ki-67 expression in cervical squamous neoplasia

Prior studies of p16 INK4a , pRb, p53 and Ki-67 expression have suggested that these markers may be preferentially expressed in cervical neoplasms. The purpose of this study was to assess the expression and the clinical significance of p16 INK4a, pRb, p53 and Ki-67 proteins in the cervical lesions. We obtained 106 cases with various categories of cervical squamous mucosa including squamous cell carcinoma (n=35), cervical intraepithelial neoplasia (CIN) II/III (n=26), CIN I (n=10), squamous metaplasia (n=15) and normal squamous mucosa (n=20). Immunohistochemical staining was performed for p16 INK4a , pRb, p53 and Ki-67 proteins in formalin-fixed and paraffin-embedded tissue sections of the uterine cervix. The evaluation of the immunohistochemical staining based on the frequencies of the expression and the mean immunoreactivity scores (IS) in each diagnostic category. p16 INK4a staining was detected in 26 of 35 cases (74.3%) of squamous cell carcinoma, in 16 of 26 cases (61.5%) of CIN II/III, in 6 of 10 cases (60%) of CIN I, in 9 of 15 cases (60%) of squamous metaplasia and negative in normal squamous mucosa. pRb expression was detected in all diagnostic categories; however, the proportion of pRb positive cells was relatively decreased in CIN II/III (38.5%) and squamous cell carcinomas (51.4%) compared to normal squamous epithelium (90%) and squamous metaplasia (73.3%). There were no significant differences in the expression of p53 in all diagnostic categories. Ki-67 expression was increased in squamous cell carcinoma (37.1%), CIN II/III (42.3%), CIN I (40%), but negative in squamous metaplasia and normal mucosa. In 35 cases of squamous cell carcinomas, multivariate analysis revealed no differences in p16 INK4a , pRb, p53, and Ki-67 expression according to the age of the patient, lymph node metastasis and the clinical stage. In conclusion, the combined use of p16 INK4a and Ki-67 immunoreactivity could improve the diagnostic specificity of squamous cell carcinoma of uterine cervix.