Expression analysis of p16 and TOP2A protein biomarkers in cervical cancer lesions and their correlation with clinico-histopathological characteristics in a referral hospital, Tanzania

Biomarkers yield important information for early diagnosis of cervical cancer. However, they are rarely applied for prognosis of cervical cancer in Tanzania, where visual inspection assay with acetic acid or Lugol's iodine and Pap test are being used as the standard screening/ diagnostic method...

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Veröffentlicht in:PloS one 2021-10, Vol.16 (10), p.e0259096-e0259096
Hauptverfasser: Zuberi, Zavuga, Mremi, Alex, Chilongola, Jaffu O, Semango, George, Sauli, Elingarami
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Mremi, Alex
Chilongola, Jaffu O
Semango, George
Sauli, Elingarami
description Biomarkers yield important information for early diagnosis of cervical cancer. However, they are rarely applied for prognosis of cervical cancer in Tanzania, where visual inspection assay with acetic acid or Lugol's iodine and Pap test are being used as the standard screening/ diagnostic methods. This was a retrospective hospital-based cross-sectional study that was conducted to assess cyclin-dependent kinase inhibitor (p16) and topoisomerase II-alpha (TOP2A) proteins expression among women seeking cervical cancer care at Kilimanjaro Christian Medical Centre, Tanzania between May 1, 2017 and May 10, 2018. Immunohistochemistry technique was used to detect the expressions of p16 and TOP2A proteins from the retrieved formalin-fixed and paraffin-embedded (FFPE) cervical biopsies. A total of 145 patients, with a mean age of 52.1 ± 12.9 years, were included in this study. Upon immunohistochemistry staining, 103 (71.0%) and 90 (62.1%) were p16 and TOP2A positive respectively. There was a strong association between histopathological class and p16/TOP2A expression levels (Fisher's exact test, p
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However, they are rarely applied for prognosis of cervical cancer in Tanzania, where visual inspection assay with acetic acid or Lugol's iodine and Pap test are being used as the standard screening/ diagnostic methods. This was a retrospective hospital-based cross-sectional study that was conducted to assess cyclin-dependent kinase inhibitor (p16) and topoisomerase II-alpha (TOP2A) proteins expression among women seeking cervical cancer care at Kilimanjaro Christian Medical Centre, Tanzania between May 1, 2017 and May 10, 2018. Immunohistochemistry technique was used to detect the expressions of p16 and TOP2A proteins from the retrieved formalin-fixed and paraffin-embedded (FFPE) cervical biopsies. A total of 145 patients, with a mean age of 52.1 ± 12.9 years, were included in this study. Upon immunohistochemistry staining, 103 (71.0%) and 90 (62.1%) were p16 and TOP2A positive respectively. There was a strong association between histopathological class and p16/TOP2A expression levels (Fisher's exact test, p&lt;0.001). Moreover, there was a strong positive correlation between p16/TOP2A and cancerous cervical lesions (Spearman's rank correlation coefficients = 0.833 and 0.687, p = 0.006 and 0.005, respectively). The age-adjusted odds ratio for predicting cervical cancer lesions were independently significant for p16/TOP2A biomarkers in FFPE cervical tissues [p16: OR = 1.142 (95% CI: 1.059-1.232, p&lt;0.001) and TOP2A: OR = 1.046 (95% CI: 1.008-1.085, p = 0.015)]. Importantly, the diagnostic performance of p16 was higher than that of TOP2A in the diagnosis of cancerous lesions from non-cancerous cervical lesions (sensitivity: 97.2% versus 77.6%, accuracy: 92.8% versus 87.8%, respectively). Our study has highlighted that over-expression of TOP2A is related to the grade of cervical intraepithelial neoplasia but does not predict prognosis in cervical cancer. Similarly, expression of p16 is related to degree of histological dysplasia and malignancy, suggesting its prognostic and predictive value in the management of cervical cancers. Further bigger studies are needed to validate their applications in the early diagnosis of cervical cancer.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0259096</identifier><identifier>PMID: 34705880</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Acetic acid ; Analysis ; Biological markers ; Biology and Life Sciences ; Biomarkers ; Biomarkers, Tumor - metabolism ; Biopsy ; Cancer ; Cell cycle ; Cellular biology ; Cervical cancer ; Cervix ; Correlation ; Correlation coefficient ; Correlation coefficients ; Cross-Sectional Studies ; Cyclin-dependent kinase ; Cyclin-Dependent Kinase Inhibitor p16 - metabolism ; Cyclin-dependent kinases ; Diagnosis ; DNA topoisomerase (ATP-hydrolysing) ; DNA Topoisomerases, Type II - metabolism ; Dysplasia ; Enzyme inhibitors ; Feasibility studies ; Female ; Genetic aspects ; Health care facilities ; Hospitals ; Human papillomavirus ; Humans ; Immunohistochemistry ; Inspection ; Iodine ; Kinases ; Lesions ; Malignancy ; Mandela, Nelson (1918-2013) ; Medical diagnosis ; Medical prognosis ; Medical screening ; Medicine and Health Sciences ; Methods ; Overexpression ; Pap smear ; Paraffin ; Paraffins ; People and Places ; Poly-ADP-Ribose Binding Proteins - metabolism ; Prognosis ; Proteins ; Retrospective Studies ; Squamous cell carcinoma ; Tanzania - epidemiology ; Uterine Cervical Neoplasms - diagnosis ; Uterine Cervical Neoplasms - metabolism ; Womens health</subject><ispartof>PloS one, 2021-10, Vol.16 (10), p.e0259096-e0259096</ispartof><rights>COPYRIGHT 2021 Public Library of Science</rights><rights>2021 Zuberi et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. 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However, they are rarely applied for prognosis of cervical cancer in Tanzania, where visual inspection assay with acetic acid or Lugol's iodine and Pap test are being used as the standard screening/ diagnostic methods. This was a retrospective hospital-based cross-sectional study that was conducted to assess cyclin-dependent kinase inhibitor (p16) and topoisomerase II-alpha (TOP2A) proteins expression among women seeking cervical cancer care at Kilimanjaro Christian Medical Centre, Tanzania between May 1, 2017 and May 10, 2018. Immunohistochemistry technique was used to detect the expressions of p16 and TOP2A proteins from the retrieved formalin-fixed and paraffin-embedded (FFPE) cervical biopsies. A total of 145 patients, with a mean age of 52.1 ± 12.9 years, were included in this study. Upon immunohistochemistry staining, 103 (71.0%) and 90 (62.1%) were p16 and TOP2A positive respectively. There was a strong association between histopathological class and p16/TOP2A expression levels (Fisher's exact test, p&lt;0.001). Moreover, there was a strong positive correlation between p16/TOP2A and cancerous cervical lesions (Spearman's rank correlation coefficients = 0.833 and 0.687, p = 0.006 and 0.005, respectively). The age-adjusted odds ratio for predicting cervical cancer lesions were independently significant for p16/TOP2A biomarkers in FFPE cervical tissues [p16: OR = 1.142 (95% CI: 1.059-1.232, p&lt;0.001) and TOP2A: OR = 1.046 (95% CI: 1.008-1.085, p = 0.015)]. Importantly, the diagnostic performance of p16 was higher than that of TOP2A in the diagnosis of cancerous lesions from non-cancerous cervical lesions (sensitivity: 97.2% versus 77.6%, accuracy: 92.8% versus 87.8%, respectively). Our study has highlighted that over-expression of TOP2A is related to the grade of cervical intraepithelial neoplasia but does not predict prognosis in cervical cancer. 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Further bigger studies are needed to validate their applications in the early diagnosis of cervical cancer.</description><subject>Acetic acid</subject><subject>Analysis</subject><subject>Biological markers</subject><subject>Biology and Life Sciences</subject><subject>Biomarkers</subject><subject>Biomarkers, Tumor - metabolism</subject><subject>Biopsy</subject><subject>Cancer</subject><subject>Cell cycle</subject><subject>Cellular biology</subject><subject>Cervical cancer</subject><subject>Cervix</subject><subject>Correlation</subject><subject>Correlation coefficient</subject><subject>Correlation coefficients</subject><subject>Cross-Sectional Studies</subject><subject>Cyclin-dependent kinase</subject><subject>Cyclin-Dependent Kinase Inhibitor p16 - metabolism</subject><subject>Cyclin-dependent kinases</subject><subject>Diagnosis</subject><subject>DNA topoisomerase (ATP-hydrolysing)</subject><subject>DNA Topoisomerases, Type II - metabolism</subject><subject>Dysplasia</subject><subject>Enzyme inhibitors</subject><subject>Feasibility studies</subject><subject>Female</subject><subject>Genetic aspects</subject><subject>Health care facilities</subject><subject>Hospitals</subject><subject>Human papillomavirus</subject><subject>Humans</subject><subject>Immunohistochemistry</subject><subject>Inspection</subject><subject>Iodine</subject><subject>Kinases</subject><subject>Lesions</subject><subject>Malignancy</subject><subject>Mandela, Nelson (1918-2013)</subject><subject>Medical diagnosis</subject><subject>Medical prognosis</subject><subject>Medical screening</subject><subject>Medicine and Health Sciences</subject><subject>Methods</subject><subject>Overexpression</subject><subject>Pap smear</subject><subject>Paraffin</subject><subject>Paraffins</subject><subject>People and Places</subject><subject>Poly-ADP-Ribose Binding Proteins - 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Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Zuberi, Zavuga</au><au>Mremi, Alex</au><au>Chilongola, Jaffu O</au><au>Semango, George</au><au>Sauli, Elingarami</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Expression analysis of p16 and TOP2A protein biomarkers in cervical cancer lesions and their correlation with clinico-histopathological characteristics in a referral hospital, Tanzania</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2021-10-27</date><risdate>2021</risdate><volume>16</volume><issue>10</issue><spage>e0259096</spage><epage>e0259096</epage><pages>e0259096-e0259096</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>Biomarkers yield important information for early diagnosis of cervical cancer. However, they are rarely applied for prognosis of cervical cancer in Tanzania, where visual inspection assay with acetic acid or Lugol's iodine and Pap test are being used as the standard screening/ diagnostic methods. This was a retrospective hospital-based cross-sectional study that was conducted to assess cyclin-dependent kinase inhibitor (p16) and topoisomerase II-alpha (TOP2A) proteins expression among women seeking cervical cancer care at Kilimanjaro Christian Medical Centre, Tanzania between May 1, 2017 and May 10, 2018. Immunohistochemistry technique was used to detect the expressions of p16 and TOP2A proteins from the retrieved formalin-fixed and paraffin-embedded (FFPE) cervical biopsies. A total of 145 patients, with a mean age of 52.1 ± 12.9 years, were included in this study. Upon immunohistochemistry staining, 103 (71.0%) and 90 (62.1%) were p16 and TOP2A positive respectively. There was a strong association between histopathological class and p16/TOP2A expression levels (Fisher's exact test, p&lt;0.001). Moreover, there was a strong positive correlation between p16/TOP2A and cancerous cervical lesions (Spearman's rank correlation coefficients = 0.833 and 0.687, p = 0.006 and 0.005, respectively). The age-adjusted odds ratio for predicting cervical cancer lesions were independently significant for p16/TOP2A biomarkers in FFPE cervical tissues [p16: OR = 1.142 (95% CI: 1.059-1.232, p&lt;0.001) and TOP2A: OR = 1.046 (95% CI: 1.008-1.085, p = 0.015)]. Importantly, the diagnostic performance of p16 was higher than that of TOP2A in the diagnosis of cancerous lesions from non-cancerous cervical lesions (sensitivity: 97.2% versus 77.6%, accuracy: 92.8% versus 87.8%, respectively). Our study has highlighted that over-expression of TOP2A is related to the grade of cervical intraepithelial neoplasia but does not predict prognosis in cervical cancer. Similarly, expression of p16 is related to degree of histological dysplasia and malignancy, suggesting its prognostic and predictive value in the management of cervical cancers. Further bigger studies are needed to validate their applications in the early diagnosis of cervical cancer.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>34705880</pmid><doi>10.1371/journal.pone.0259096</doi><tpages>e0259096</tpages><orcidid>https://orcid.org/0000-0003-0150-2005</orcidid><orcidid>https://orcid.org/0000-0001-7226-0168</orcidid><oa>free_for_read</oa></addata></record>
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subjects Acetic acid
Analysis
Biological markers
Biology and Life Sciences
Biomarkers
Biomarkers, Tumor - metabolism
Biopsy
Cancer
Cell cycle
Cellular biology
Cervical cancer
Cervix
Correlation
Correlation coefficient
Correlation coefficients
Cross-Sectional Studies
Cyclin-dependent kinase
Cyclin-Dependent Kinase Inhibitor p16 - metabolism
Cyclin-dependent kinases
Diagnosis
DNA topoisomerase (ATP-hydrolysing)
DNA Topoisomerases, Type II - metabolism
Dysplasia
Enzyme inhibitors
Feasibility studies
Female
Genetic aspects
Health care facilities
Hospitals
Human papillomavirus
Humans
Immunohistochemistry
Inspection
Iodine
Kinases
Lesions
Malignancy
Mandela, Nelson (1918-2013)
Medical diagnosis
Medical prognosis
Medical screening
Medicine and Health Sciences
Methods
Overexpression
Pap smear
Paraffin
Paraffins
People and Places
Poly-ADP-Ribose Binding Proteins - metabolism
Prognosis
Proteins
Retrospective Studies
Squamous cell carcinoma
Tanzania - epidemiology
Uterine Cervical Neoplasms - diagnosis
Uterine Cervical Neoplasms - metabolism
Womens health
title Expression analysis of p16 and TOP2A protein biomarkers in cervical cancer lesions and their correlation with clinico-histopathological characteristics in a referral hospital, Tanzania
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