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- Title
Systematic review and meta analysis (SRMA) of biomarker performance in the tissue-based diagnosis of adenocarcinoma of the uterine cervix.
- Authors
Lee, Sandra; Rose, M. Sarah; Zhao, Rachel; Duggan, Máire A.
- Abstract
Objective: Immunohistochemistry (IHC) is widely relied on to support a histopathological diagnosis of adenocarcinoma of the uterine cervix. The primary objective of this SRMA is to determine the sensitivity and specificity of single IHC biomarkers and combinations of IHC biomarkers for the diagnosis of cervical adenocarcinoma in situ (AIS) and cervical mucinous adenocarcinoma (CMA). Methods: The initial search was completed between Jan 18, 2013 and Feb 21, 2014. A second search was completed June 30, 2014. IHC expression patterns in AIS and CMA classified per WHO 2003 were compared to 1) normal endocervix (NE) 2) benign endocervical lesions (BEL) including microglandular hyperplasia, hyperplasia NOS, tunnel clusters, and Nabothian cysts, and 3) benign endocervical lesions with endometrioid differentiation (BELED) including tuboendometrioid metaplasia and endometriosis. Results: Of 109 articles selected for full review, 60 were selected for inclusion. p16 was the only IHC marker with enough published data for a traditional meta analysis. 7 articles reported results for p16 IHC with appropriate controls. The definition of positive p16 staining was variable and was defined as strong nuclear or cytoplasmic staining in only one article. Many publications considered any staining to be positive. Any positive p16 expression is highly sensitive and specific for AIS (0.97 [0.74-1.0]; 0.98 [0.78-1.00]) and CMA (0.93 [0.87-0.97]; 0.98 [0.78-1.00]) in comparison to NE. In comparison to BEL and BELED, sensitivity remained high for AIS (0.98 [0.67-1.00]; 0.98 [0.69-1.00]) and CMA (0.91 [0.80-0.96]; 0.98 [0.74-1.00]). However, specificity was lower in comparison to BEL (AIS 0.84 [0.52-0.96]; CMA 0.83 [0.74-0.96]) and highly variable in comparison to BELED (AIS 0.31 [0.0-0.99]; CMA 0.34 [0.0-0.99]) for which the sample size was very small (24 total controls). Conclusion: Positive expression of p16 supports a diagnosis of AIS and CMA of the cervix in comparison to BEL without endometrioid differentiation. p16 is expressed by BELED and therefore is not specific for the diagnosis of AIS or CMA in this context. The majority of studies did not consider a mosaic pattern of p16 or block positive p16 staining as distinct patterns of p16 expression and this may have contributed to the poor performance of p16 to distinguish AIS and CMA from BELED.
- Publication
Canadian Journal of Pathology, 2016, Vol 8, p44
- ISSN
1918-915X
- Publication type
Article