Expression of Epithelial Cadherin and P16INK4 in High Risk Human Papilloma Virus Infection of Cervical Intraepithelial Lesion in Attendees of Nnamdi Azikiwe University Teaching Hospital, Nnewi, Anambra State, Nigeria.
Ezeofor C P, Ezejiofor I F, Asomugha A L, Ogenyi S I, Olaofe OO, Osonwa C N, and, Ilegbedion I G
Abstract
Reduced expression of E.cadherin is regarded as one of the main molecular events in dysfunction of the cell adhesion system, triggering cancer invasion and metastasis and disrupt cell cycle regulation. Loss of cell cycle regulation is main event in cancer. P16INK4 is a well known surrogate marker for hr-HPV infection. Hence, there is need to determine the role of E.cadherin, in progression of high –risk human papilloma virus (hr-HPV) infection in uterine cervix. The aim of this study was to determine expression pattern of E.cadherin and P16INK4a their role in progression of high-risk HPV type of cervical intraepithelial neoplasm or lesions (CIN/CILs) in attendees of Nnamdi Azikiwe University Teaching Hospital, Nnewi, Anambra State, Nigeria. Eighty-six (86) cases of cervical squamous intraepithelial lesion (cSIL) were included in the study. Immunohistochemistry was performed on both test and control lesions for E.cadherin and P16 protein. The immunoreactivity were evaluated for each marker and the values were statistically analysed. Out of the 86 cases of CILs subjected to E.cadherin and P16INK4a monoclonal antibodies, 55.8% (48/86 cases) had an initial, pre-immunohistochemical diagnosis as CIN 1 (Low-grade squamous intraepithelial lesion; LSIL) while 44.2% (38/86cases) were high-grade squamous intraepithelial lesions (HSIL). However, on application of monoclonal antibodies of E.cadherin, and P16, majority of LSIL had a change of diagnosis to Negative squamous intraepithelial lesions (NSIL) 21/48 (43.8%) and chronic cervicitis 11/48 (27.1%) while 16/48 cases (35.4%) were finally retained as LSIL. Of 38 initially diagnosed as HSIL lesions {CIN2, CIN3, and Carcinoma In-situ; (CIS) 35 cases (92.1%) were concordant with previous diagnosis while three cases were regrouped as CIN 1 (one case) and chronic cervicitis (2 cases). Therefore, the total number of CIN 1 was 17 cases and chronic cervicitis were 13 cases. The rate of E.cadhe
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References
Journal ofClinical Virology.32:16–24.
Brisson, M, Kim, J.J, Canfell K, Drolet, M. and Gingras,G., Burger A E., Martin, D., Simme,
T.K., Barnard, E., Boily, C.M,. Sy, S., Regan, C., Keane, A., Caruana, N., Nguyen,
N.T.D., Smitth, A.M., Laprise, J. Jit, M., Alary, M., Bray, F. Fidarova, E., Elsheikh, F.,
Bloeme, P.J.N., Broutet, N. and Hutubessy. R. (2020). Impact of HPV vaccination and
cervical screening on cervical cancer elimination: a comparative modelling analysis in 78
low-income and lower-middle-income countries. The Lancet 395: 575-590
Cano, A., Pérez-Moreno, M.A., Rodrigo, I. Locascio, F. and Nieto, M.A.(2000) The transcription
factor Snail controls epithelial-mesenchymal transitions by repressing E-cadherin
expression. Nature Cell Biology2(2):76–83.
Canfell, K., Sitas, F. and Beral, V. (2006). Cervical Cancer in Australia and the United
Kingdom: Comparison of Screening Policy and Uptake and Cancer Incidence and
Mortality. Medical Journal of Australaria185 (9): 482-486.Darragh, T.M., Colgan T.J.,
Heller D.S., Henry M.R., Luffm, R.D., McCalmont T., Nayar R., Palesky, J.M., Stoler,
M.H.,Wilkinson, E.J., Zaino, R.J. and Wilbur, D.C. (2012). The lower anogenital
squamous terminology standardization project for HPV-associated lesions: Background
and consensus recommendations from the College of American
Chen, C.C. Chiu,H.H.,Yen,L.C.,Chang,Y.F. Chang, M.S.,Tsai, J.R. and Chen,Y.F.(2010). Over
expression of EGFR-related genes in the circulation is highly correlated with EGFR
mutants and overexpression in paired cancer tissue from patients with non small cell lung
cancer. Oncology Report23 (3) 639 -645
Chen, X.J., Han, L.F., Wu, X.G., Wei, W.F., Wu, L.F., Yi, H.Y., Yan, R.M., Bai, X.Y., Zhong,
M. and Yu Y.H.(2017). Clinical Significance of CD163+ and CD68+ Tumor-Associated
Macrophages in High-Risk HPV-Related Cervical Cancer. Journal of cancer 8:3868–
3875
Darragh, T.M., Colgan T.J., Heller D.S., Henry M.R., Luffm, R.D., McCalmont T., Nayar R.,
Palesky, J.M., Stoler, M.H.,Wilkinson, E.J., Zaino, R.J. and Wilbur, D.C. (2012). The
lower anogenital squamous terminology standardization project for HPV-associated
lesions: Background and consensus recommendations from the College of American
Faleiro-Rodrigues, C. and Lopes, C. (2004). E-cadherin, CD44 and CD44v6 in squamous
intraepithelial
lesions
and
invasive
carcinomas
of
the
uterine
cervix:
an
immunohistochemical study. Pathobiology71:329–336
Gumbiner BM (1999). Cell adhesion:The molecular basis of tissue architecture and
morphogenesis. Cell84:345–357.
Information centre of HPV and cancer (IOC) (2023). Nigeria Papilomavirus and Related Cancer,
Fact sheet 2023. https://hpvcentre.net . Accessed online on 20th July, 2024
Izadi-Mood, N., Asadi, K., Shojaei, H., Sarmadi, S., Ahmadi, S.A., Sani, S., Chelavi, L.H.
(2012). Potential diagnostic value of P16 expression in premalignant and malignant
cervical lesions. Journal of Research in Medical Sciences: The Official Journal of Isfahan
University of Medical Sciences.2012;17(5)
Klaes R, Friedrich T, Spitkovsky D, Ridder R, Rudy W, Petry U,(2006) Overexpression of
p16(INK4A) as a specific marker for dysplastic and neoplastic epithelial cells of the
cervix uteri. International Journal of Cancer. 92 (2)
Kawasaki, T., Nosho, K., and Ohnishi, M. Suemolo, Y. Kirkner, J.G.,Dehari, R., Meyerhardt,
J.J., Fuchs, C. and Ogino, S.(2007) “Correlation of ?-catenin localization with
cyclooxygenase-2 expression and CpG island methylator phenotype (CIMP) in colorectal
cancer,” Neoplasia, 9, (7) :569–577
Menka, A., Philip, C.,Vogeeelmann, R., lSeidel, B.,Lutz, P.M.A dler, G. and Wedlich,
D.(2001).Down -regulation of E.cadherin Gene expression by collagen type 1 and type
11 in Pancreatic cancer cell line. Cancer Research61(8):3508 – 3517.
Mitra, A., MacIntyre, D.A., Lee, Y.S., Smith, A., Marchesi, J.R., Lehne, B., Bhatia, R., Lyons,
D., Paraskevaidis, E., Li J.V., (2015). Cervical Intraepithelial Neoplasia Disease
Progression Is Associated with Increased Vaginal Microbiome Diversity. Scienctific
Report5:16865.
Nigeria Fact Sheet (2020). Data visualization for tools exploring the global cancer burden.
Available
from
https:/e/gco.iarc.fr/today/data/factsheets/populations/566-nigeria-fact-
sheets.pdf.Accessed on line on January 31, 2023.
Pelosi, G., Scarpa, A., Puppa G., Veronesi G., Spaggiari, L.,Pasini, F.,Maisonneuve P.,
Lannucci, A., Arrigoni G. and Viale, G. (2005)“Alteration of the E-cadherin/?-catenin
cell adhesion system is common in pulmonary neuroendocrine tumors and is an
independent predictor of lymph node metastasis in atypical carcinoids,” Cancer,103(6):
1154–1164
Sarma U, Das GC , Sarmah B. (2021)Predictive Value of Marker of Proliferation Ki-67 and Cell
Cycle Dependent Protein kinase Inhibitor P16INK4a in Cervical Biopsy to Determine Its
Biological Behaviour Asian Pacific journal of cancer prevention:;22(7)5
Shakil, S., Maheshwari, V., Afroz, N. and Ahmed, M. (2023) Diagnostic and Prognostic
Significance of E-cadherin and ?-catenin in Oral Squamous Cell Carcinoma with or
without Lymphnode Metastasis International. Journal of Medical Research & Health.
Sciences.12(7): 54-63
Singhai, U., Lamba, S.,Kumar A. and Nand U.(2018). Pattern of epithelial cell abnormalities on
cervical Papanicolour Smears in hospital of North India: A retrospective study. Annals of
Pathology and Lab Median 5 (3):250 – 255
Tsanou, E., Peschos, D., Batistatou, A., Charalabopoulos, A. and Charalabopoulos, K. (2008).
The E-cadherin adhesion molecule and colorectal cancer. A global literature
approach. Anticancer Research.28:3815–3826.
WHO (2022).Cervical cancer roadmap- essential. United action against cancer. Accessed online
on 13 February, 2023
Yang, N. and Sheridan, A.M. (2014). Cell cycle. Encyclpedia of Toxicology. Third edition.
Elsevier. Pp 753 – 758.
Zur Hausen H. (1996). Papillomavirus infections--a major cause of human cancers. Biochimicaet
Biophysica Acta.1288 (2):55-78.