Diagnostic value of p16 and Ki-67 expression in cervical glandular intraepithelial disease: A review

Cervical adenocarcinoma has been increasing in frequency, particularly among young women. Its diagnosis still presents many challenges. In addition to the difficulty in accessing the lesion, the lack of well-established criterias for cytological and histological diagnosis, and colposcopic images that are often not very clear, there are many benign situations that mimic glandular diseases. Immunohistochemistry has been used to aid this diagnosis. The purpose of this review is to evaluate the data available in the literature related to the use of p16 and Ki-67 as an auxiliary tool in the diagnosis of glandular disease.

Original articles were searched in the PUBMED/MEDLINE, EMBASE, SCOPUS and BVS using different combinations of keywords and descriptors.

Of the 83 initial articles, 10 were selected. The criterias used for immunohistochemical interpretation showed many differences. The studies compared benign pathologies to malignant pathologies and some used panels with different immunomarkers while others used only p16. P16 showed an intense staining pattern in malignant pathologies, despite some studies have shown a negative pattern in adenocarcinoma. This can be explained by the histological subtype, not always related to HPV. Some studies have shown immunopositivity for p16 in normal tissues, tubal metaplasia and cervical endometriosis, but the staining pattern was never intense, as in malignant tissues. Ki-67 showed a more intense staining in AIS and adenocarcinoma tissues and was also present in normal tissues, mainly in tubal metaplasia and cervical endometriosis.

Biomarkers have proved to be important tools in aiding the diagnosis of glandular lesions, either alone or in panels. Standardization in the interpretation of immunochemistry is required.