A cocktail of MCM2 and TOP2A, p16 INK4a and Ki-67 as biomarkers for the improved diagnosis of cervical intraepithelial lesion

Abstract

The purpose of this paper was to explore the immunohistochemistry (IHC) results for a cocktail of minichromosome maintenance protein 2 (MCM2) and topoisomerase IIα (TOP2A), p16 INK4a and Ki-67 as biomarkers for the diagnosis of cervical intraepithelial neoplasia (CIN), improving the routine interpretation of cervical histopathology. 133 cases of CIN were collected from the archival data. All routine hematoxylin and eosin (HE)-stained slides of the subjects were re-examined independently by three senior pathologists, to provide a "consensus diagnosis". Immunohistochemistry for the three biomarkers was performed, and the results were reviewed independently of the corresponding archival diagnosis to make a "diagnosis assisted by IHC" by the original pathological practitioners. The diagnosis accordance rate of the archival original diagnosis with the "consensus diagnosis" and the "diagnosis assisted by IHC" with the "consensus diagnosis" were verified by Fisher's exact test. The results showed that raw agreement between the original HE diagnosis and the "consensus diagnosis" was 88.55%, and raw agreement between the "diagnosis assisted by IHC" and the "consensus diagnosis" was 95.78%. The latter was significantly higher than the former (Fisher's exact test, p = 0.023). In conclusion, the three biomarkers had a high degree of sensitivity and specificity, and appear to be a useful and reliable diagnostic adjunct to improve the routine diagnosis, and reduce inter-observer variability in cervical biopsy specimens.

Bioinformatics analysis and identification of potential genes related to pathogenesis of cervical intraepithelial neoplasia

“…Our results show that TOP2A and RFC4 play an important role in this process. TOP2A is regarded as a biomarker for the improved diagnosis of CIN 26 . Recent study has shown that TOP2A protein is expressed in cells with aberrant S-phases and including HPV-transformed cells in association with elevated expression of the HPV E6/E7 proteins 27 .…”

“…Recent study has shown that TOP2A protein is expressed in cells with aberrant S-phases and including HPV-transformed cells in association with elevated expression of the HPV E6/E7 proteins 27 . It is worth noting that many studies have shown that TOP2A expression level is significantly correlated with CIN grade 26,28 . In addition, RFC4 accelerated G1 to S phase progression, and promoted the proliferation of cervical cancer cells and the growth of cervical cancer 29 .…”

An interaction network driven approach for identifying biomarkers for progressing cervical intraepithelial neoplasia

“…Previous studies have shown that overexpression of MCM2 can be utilized to increase the diagnosis of CIN and squamous cell carcinoma (SCC) 16 , 17 . Moreover, a cocktail of MCM2 and TOP2A , p16INK4 and Ki-67 has been suggested as biomarkers for better diagnosis of CIN lesion 18 .…”

Original article Proliferation index revisited in neuroblastic tumors

“…Several tumor-type criteria for PI establishment have been elaborated. Digital image analysis systems can further improve the reliability of PI assessment [1,13,26].…”

“…In adult cancers, such as neuroendocrine tumors, breast carcinoma, lymphomas, prostate cancer and gliomas, the Ki-67 labeling index is included in the routine diagnostics, having therapeutic implications [1,2,27]. Likewise, the assessment of topoisomerase II alpha (Topo2A) expression emerges as a prolifera-tion marker in several cancer types, including brain tumors [12,26,29]. Ki-67 nuclear protein is required for maintaining cell proliferation, as it is detectable in all active phases of the cell cycle (G1, S, G2 and M) but absent in the resting phase G0 [21,28].…”