Assessment of Ki-67 Antigen Immunostaining in Squamous Intraepithelial Lesions of the Uterine Cervix:Correlation With the Histologic Grade and Human Papillomavirus Type

Abstract

A formalin-fixation and paraffin-processing resistant epitope of Ki-67 cell proliferation-associated antigen was immunohistochemically detected by the MIB-1 monoclonal antibody (Immunotech, Marseille, France) in 25 routinely processed cervical biopsies showing normal squamous epithelium or squamous metaplasia and in 65 cervical intraepithelial lesions (SILs) (44 low grade and 21 high grade SILs) with human papillomavirus (HPV) infection. Expression of Ki-67 antigen was exclusively confined to the parabasal and basal layers of normal and metaplastic epithelium. There was no significant difference of Ki-67 antigen immunostaining between normal cervical biopsies and cases of squamous metaplasia. In SIL specimens, the staining was markedly increased in the parabasal and basal layers and Ki-67-positive cells were also distributed in the intermediate (low grade SIL) or all layers of epithelium (high grade SIL). Statistically significant differences for the density of Ki-67 antigen-labeled cells, which were assessed with an image analysis system, were found in comparisons between normal or metaplastic epithelium and SILs (P < .001) and between low grade SILs and high grade SILs (P < .001). In our series of SILs, HPV 16/18 and 31/33/35/novel types, which were found in both low grade and high grade SILs, were significantly associated with higher densities of Ki-67 antigen-positive cells than HPV 6/11 types that were found exclusively in low grade SILs. There was no significant difference found between the densities of Ki-67 antigen-labeled cells in HPV 16/18-positive and HPV 31/33/35/novel types-positive tissues in our series of SILs taken as a whole or when segregating SILs into low grade and high grade.

p16INK4a Expression Correlates with Degree of Cervical Neoplasia: A Comparison with Ki-67 Expression and Detection of High-Risk HPV Types

“…Although Ki-67 has been shown in several studies to be useful in diagnosing cervical neoplasia, our study shows that whereas Ki-67 expression is a sensitive marker of cervical neoplasia, overexpression is linked to both inflammation and reactive/atypical changes; p16 INK4a showed no such association (7,10,14,22). This is to be expected as inflammation is associated with increased cell turnover and reactive cervical squamous metaplasia has been shown to overexpress Ki-67 (10).…”

Variations of mitotic index in normal and dysplastic squamous epithelium of the uterine cervix as a function of endometrial maturation

“…As previously noted, the intraepithelial distribution, density, nature (typical or atypical) of mitotic figures have emerged as important pathologic criteria for distinguishing low-grade cervical intraepithelial neoplasia from high-grade cervical intraepithelial neoplasia and for distinguishing high-grade cervical intraepithelial neoplasia from potential histologic mimics such as transitional metaplasia, atrophy or immature squamous metaplasia. [3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19] Mitotic figures in low-grade cervical intraepithelial neoplasia should be confined to basal third of the epithelium and should not be numerous and should only rarely be atypical. 37 High-grade cervical intraepithelial neoplasia, in contrast, may show numerous mitoses including numerous abnormal forms throughout the epithelium.…”

“…[3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19] Compared to the endometrium and vaginal epithelium, where marked variations in the estrogen receptor (ER) content occur during the menstrual cycle, much less cyclic variation of ER expression occurs in the cervical lining. [20][21][22] Nonetheless, it has long been recognized that cervical squamous epithelial cells contain sex-steroid receptors and hence, their proliferation and differentiation are influenced, to some extent, by the menstrual cycle and/ or sex-steroid hormonal levels.…”

Expression of the p16INK4a and Ki-67 in relation to the grade of cervical intraepithelial neoplasia and high-risk human papillomavirus infection

“…[9][10][11][12] Ki-67 is a well-known cell proliferation marker and which may be used for grading CIN. [13][14][15] To evaluate the clinical values of p16 and Ki-67 expressions, we examined the p16 and Ki-67 expressions in CIN and investigated the associations of high-risk HPV infection with the p16 and Ki-67 expressions.…”