From Cell Biology to Tissue Engineering



Beyond p16 immunostaining: an overview of biomarkers in anal squamous intraepithelial lesions

Andreia Albuquerque1, Elisabete Rios1,2,3 and Rui Medeiros1,4,5,6

1Faculty of Medicine of the University of Porto, 2Pathology Department Centro Hospitalar São João, 3Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP), 4Molecular Oncology and Viral Pathology Group, IPO Research Center, Portuguese Oncology Institute, 5Research Department, Portuguese League Against Cancer and 6CEBIMED, Faculty of Health Sciences, Fernando Pessoa University, Porto, Portugal

Offprint requests to: Andreia Albuquerque, Gastroenterologist, MD, Faculty of Medicine of the University of Porto, Alameda Professor Hernâni Monteiro, 4200-319 Porto, Portugal. e-mail: a.albuquerque.dias@gmail.com

Summary. Histological grading of squamous intraepithelial lesions or intraepithelial neoplasia is fundamental for clinical management and for assessment of the risk of progression. Biomarkers are important for assisting correct grading of these lesions, reducing inter and intraobserver variability and most promising, for prognosis. Although p16 is the most studied biomarker in this setting, there are several other biomarkers that have been studied, reflecting also the need to find a better single or association option that can be more suitable, especially for classification purposes. A PubMed and Embase search was conducted from their inception until April 2018, aiming to identify biomarkers evaluated in histological samples of anal squamous intraepithelial lesions, other than p16. Information on "Ki-67", "ProEx™ C", "p53", "human papillomavirus L1 capsid protein", "stathmin-1", "minichromosome maintenance protein", "p21", "proliferating cell nuclear antigen", "histones", "human papillomavirus E4", "chromosomal abnormalities" and "methylation" was collected and reviewed. From these, the most studied biomarker was by far Ki-67. In many cases there were few studies performed for each biomarker, with no clear standardized interpretation of the immunostaining. An increased positive rate with more severe grades of lesions was shown in many cases. Prognostic data are limited and need to be further validated. Histol Histopathol 34, 201-212 (2019)

Key words: Anal squamous intraepithelial lesions, Anal intraepithelial neoplasia, Biomarkers, Immunohisto-chemistry, Methylation

DOI: 10.14670/HH-18-053