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

Abstract

Introduction 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. 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. Results 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<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<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). Conclusion 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.

Sensor detection in gynaecological medicine

“…111 OPN was observed to be upregulated in cervical cancer, 110 while p16 and TOP2A overexpression were related to precancer and cancer. 111 However, OPN could only discriminate between healthy controls and advanced cervical cancer, suggesting OPN is effective as a late-stage biomarker for cervical cancer. Although TOP2A expression was upregulated, it was not stage-dependent; p16's stage-dependent expression suggests it could be used as a prognostic biomarker.…”

“…Other protein biomarkers include osteopontin (OPN) [110] protein cyclin-dependent kinase inhibitor (p16), and topoisomerase II-alpha (TOP2A) [111]. OPN was observed to be upregulated in cervical cancer, [110] while p16 and TOP2A overexpression were related to precancer and cancer [111].…”

“…Other protein biomarkers include osteopontin (OPN) [110] protein cyclin-dependent kinase inhibitor (p16), and topoisomerase II-alpha (TOP2A) [111]. OPN was observed to be upregulated in cervical cancer, [110] while p16 and TOP2A overexpression were related to precancer and cancer [111]. However, OPN could only discriminate between healthy controls and advanced cervical cancer, suggesting OPN is effective as a late-stage biomarker for cervical cancer.…”

“…However, OPN could only discriminate between healthy controls and advanced cervical cancer, suggesting OPN is effective as a late-stage biomarker for cervical cancer. Although TOP2A expression was upregulated, it was not Please do not adjust margins Please do not adjust margins stage-dependent; p16's stage-dependent expression suggests it could be used as a prognostic biomarker [111]. While HPV testing has become a significant screening technique, it does not effectively predict prognosis since over 90% of HPV infections are cleared by the immune system [36].…”

“…Although TOP2A expression was upregulated, it was not stage-dependent; p16's stage-dependent expression suggests it could be used as a prognostic biomarker. 111 While HPV testing has become a significant screening technique, it does not effectively predict prognosis since over 90% of HPV infections are cleared by the immune system. 36 In this case, ideal biomarkers would predict the likelihood of an HPV infection to transform into invasive carcinoma.…”