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. 2022 May 9;12(1):7613.
doi: 10.1038/s41598-022-11584-z.

The value of Ki67 for the diagnosis of LSIL and the problems of p16 in the diagnosis of HSIL

Jixuan Liu  1 , Sanmei Su  1 , Yafang Liu  2
Affiliations

The value of Ki67 for the diagnosis of LSIL and the problems of p16 in the diagnosis of HSIL

Jixuan Liu et al. Sci Rep. .

Abstract

p16 and Ki67 are immunohistochemical markers related to cervical squamous intraepithelial lesions. p16 has been widely used to assist in the diagnosis of high-grade squamous intraepithelial lesions. However, a conclusion about the role of Ki67 in the diagnosis of squamous intraepithelial lesions has not been established. The aim of this study was to analyze the role of p16 and Ki67 immunohistochemical staining in assisting cervical squamous intraepithelial lesions. This study performed immunohistochemical staining for p16 and Ki67 on 1024 cervical biopsy specimens at our hospital to compare the differences between p16 and Ki67 in different cervical lesions using the chi-squared test and Fisher's exact test. This study also evaluated the value of Ki67 for the diagnosis of low-grade squamous intraepithelial lesions (LSILs) using the receiver operating characteristic curve. The results indicated that Ki67 had high specificity and sensitivity in distinguishing LSIL from normal cervix. p16 was diffusely and strongly positive in some LSILs, and some problems were encountered in the interpretation of p16 staining. Therefore, we believe that Ki67 can be used as an immunohistochemical marker to help in the diagnosis of LSIL, to distinguish lesions that are difficult to morphologically determine and to avoid misdiagnosis. The practical application of p16 staining is still problematic. It may be necessary to find other auxiliary means to distinguish this small proportion of cervical lesions.

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Conflict of interest statement

The authors declare no competing interests.

Figures

Figure 1
Figure 1
(A) Histological image of LSIL (B) Histological image of LSIL (C) Histological image of the cervix not infected by HPV (D) Cervical biopsy tissue showed some suspicious morphological features of LSIL (E) The morphology of cervical biopsy is between LSIL and HSIL.
Figure 2
Figure 2
(A) P16 immunohistochemical staining showed negative (B) P16 immunohistochemical staining showed local weak positive(C) P16 immunohistochemical staining showed diffuse and strong positive (D) Histology shows the performance of LSIL (E) P16 immunohistochemical staining showed diffuse and strong positive over 1/3 layer of squamous epithelium.
Figure 3
Figure 3
(A) Histologically interpreted as suspicious LSIL (B) P16 staining shows diffuse and strong positive staining in the lower part of the squamous epithelium (C) Morphology is difficult to determine whether it is LSIL or HSIL (D) P16 showed moderate positive in some areas and weakly positive in some areas (E) Histologically interpreted as LSIL (F) P16 shows uneven positivity of moderate intensity (G) The glandular epithelium showed obvious atypia (H) P16 shows uneven positivity of moderate intensity.
Figure 4
Figure 4
(A) Normal cervical squamous epithelium (B) Ki67 was mainly expressed in basal layer and parabasal layer in normal cervical squamous epithelium (C) Histological picture of LSIL (D) In LSIL ,Ki67 was not only expressed in basal layer and parabasal layer, but also expressed in 2 / 3 of squamous epithelium. (E) Histological picture of HSIL (F) In HSIL ,Ki67 was not only expressed in basal layer and parabasal layer, but also expressed in 2 / 3 of squamous epithelium. (G) Papillary hyperplasia of cervical squamous epithelium (H)In Papillary hyperplasia of cervical squamous epithelium, Ki67 was not only expressed in basal layer and parabasal layer, but also expressed in the axis of the vessel.
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