The prognostic signifi cance of p16, Ki-67, p63, and CK17 expression determined by immunohistochemical staining in cervical intraepithelial neoplasia 1

Abstract

ObjectiveTo evaluate the prognostic signifi cance of p16, p63, and cytokeratin (CK) 17 expression determined by immunohistochemical staining in cervical intraepithelial neoplasia (CIN) 1. MethodsBiopsy tissue samples from 33 patients diagnosed with CIN 1 were stained immunohistochemically for p16, Ki-67, p63, and CK17. The staining results were correlated with the clinical course of the disease. ResultsSeventeen of 18 (94.4%) p16-negative patients experienced regression, and only 1 patient (5.6%) developed persistent disease. Fifteen of the 16 (93.8%) Ki-67-negative patients experienced regression, and 1 patient (6.3%) developed persistent disease. Negative p16 and Ki-67 expression correlated signifi cantly with disease regression (P=0.004 and P=0.017, respectively). Fourteen of 15 (93.3%) patients negative for both p16 and Ki-67 experienced regression, and 1 patient negative for both p16 and Ki-67 (6.7%) developed persistent disease. The expression levels of p63 and CK17 were not signifi cantly associated with disease regression or persistence (P=0.149 and P=0.642, respectively). Ten of the 13 (76.9%) p16-positive patients had a high-risk HPV infection. Highrisk HPV infection was signifi cantly associated with p16 expression (P=0.049). ConclusionCIN 1 with p16-or Ki-67-negative immunohistochemical staining was associated with spontaneous disease regression. The p63 and CK17 expression patterns were not related to the behavior of CIN 1.

Significance of p53, pRb and Ki-67 markers in Cervical intraepithelial lesion and Malignancy

“…This will further result in transformation to high grade dysplasia and progresses to invasive carcinoma (Kalof AN, 2007;Magaldi TG, 2012).The multistep process of carcinogenesis is based directly or indirectly on cell proliferation. Ki-67 is a nuclear proliferation associated antigen and a well known cell proliferation marker (Kim SM, 2001). Cell proliferation has been described as an additional parameter useful in the prognostic evaluation of cervical cancer (Agnaldo LS, 2004;Qiangxiu W, 2004).…”

“…Ki-67 expression is greater in CIN samples than in normal/metaplastic epithelium and Ki-67 staining is stronger in high-grade CIN than in low-grade CIN. Therefore, Ki-67 is usually used to differentiate and grade CIN (Godoy AEG, 2014;Kim SM, 2001). One study has shown increased expression of Ki-67 in SCC, CIN I/II/III but negative expression in squamous metaplasia and normal squamous mucosa (Son SM, 2012).…”

Designing of CD8⁺ and CD8⁺-overlapped CD4⁺ epitope vaccine by targeting late and early proteins of human papillomavirus

“…62,63 systems biology-based virtual cancer pathway prediction and kinetics A literature survey was performed to collect the required information about the selected protein sequences to design and predict the peptides involved in biochemical pathways. [64][65][66][67][68][69][70][71][72][73][74] A mathematical and computational model of the entire HPV45 infection signaling pathway interacting with specific genes in the presence of peptides was developed and was visualized using CellDesigner v4.4 modeling tool. 75 Nodes in the pathway represented the entities, and edges represented connectivity of one node to another, which was closely related to each other.…”

“…In addition, the CAVPVTTRY 4-12 epitope of E4 protein was predicted to have binding affinity for HLA-(A*29, A*30, B*58, B*35) allotypes (Table 1C). Among the five epitopes of E6 protein, RTEVYQFAF [41][42][43][44][45][46][47][48][49] and YSRIRE-LRY [72][73][74][75][76][77][78][79][80] were predicted to have binding affinity for HLA-A*(32:01, 29:02) and HLA-B*58: 01 MHC class I alleles (Table 1D). Out of 13 MHC-binding E7 peptides (Table 1E), STLSFVCPW [93][94][95][96][97][98][99][100][101] (HLA-A*32:01, HLA-B*58:01, HLA-B*57:01), LQQLFLSTL [87][88][89][90][91][92][93][94][95] (HLA-A*02:06), and QLFLSTLSF [89][90][91][92][93][94][95][96]…”

“…Out of 13 MHC-binding E7 peptides (Table 1E), STLSFVCPW [93][94][95][96][97][98][99][100][101] (HLA-A*32:01, HLA-B*58:01, HLA-B*57:01), LQQLFLSTL [87][88][89][90][91][92][93][94][95] (HLA-A*02:06), and QLFLSTLSF [89][90][91][92][93][94][95][96][97] (HLA-B*15:02, HLA-B*15:01, HLA-A*32:01) were predicted to have a binding affinity of IC 50 <200 nm. Furthermore, three out of seven epitopes of L1 protein, such as HVEEYDLQF [51][52][53][54][55][56][57][58][59] , TLTAEVMSY [67][68][69][70][71][72][73][74][75] , and LTAEVMSYI [68][69]…”