Available online 5 December 2022, 154261
Author links open overlay panelABSTRACTIntroductionHIK1083 and MUC6 have been used as immunohistochemical markers to differentiate gastric-type adenocarcinoma (GTAC) from other endocervical adenocarcinomas. We aimed to assess their diagnostic accuracy through a systematic review and meta-analysis.
MethodsThree electronic databases were searched from their inception to July 2022 for all studies assessing the expression in endocervical GTAC vs other endocervical adenocarcinomas. Diagnostic accuracy was assessed as sensitivity, specificity, positive likelihood ratio (LR+), negative likelihood ratio (LR-), diagnostic odds ratio (DOR), and area under the curve (AUC) on SROC curves.
ResultsFour studies with 343 patients were included. HIK1083 showed sensitivity=0.64, specificity=0.94, LR+=8.30, LR-=0.38, DOR=33.36, AUC=89.9%. MUC6 showed sensitivity=0.51, specificity=0.74, LR+=1.96, LR-=0.71, DOR=3.48, AUC=72.8%.
ConclusionHIK1083 showed high specificity and low sensitivity as a marker of GTAC, with moderate overall accuracy; MUC6 showed moderate specificity and low sensitivity, with low overall accuracy.
Section snippetsINTRODUCTIONCervical carcinoma is the most common gynecological malignancy in underdeveloped countries [1]. About 90% of cervical carcinomas are squamous cell carcinoma, while the remaining cases are adenocarcinomas. The vast majority of cervical carcinoma is caused by persistent HPV infection [2], [3]. However, a subset of adenocarcinomas is unrelated to HPV infection. Gastric-type adenocarcinoma (GTAC) is an uncommon type of HPV-independent endocervical malignancy. Compared to HPV-related
MATERIALS AND METHODSThis study was performed following a priori-defined methods, based on previously published systematic reviews and meta-analyses [11], [12]. Two authors independently performed electronic search, stud selection, data extraction, risk of bias assessment, and data analysis. The study was reported according to the PRISMA guidelines [13].
Study selection and characteristicsThe study selection process led to the identification of 7 suitable studies [4], [5], [6], [7], [8], [9], [10]. Out of these studies, 3 showed overlapping patient data [5], [9], [10], and thus only the largest one was included [9]. Another study selected 13 GTAC and 56 n-GTAC but performed HIK1083 and MUC6 only on GTAC cases [8]. Therefore, 4 studies [4], [6], [7], [9] with 343 endocervical adenocarcinoma, including 70 GTACs and 273 n-GTACs (265 usual-type, 7 intestinal-type, and a mixed
DISCUSSIONThis systematic review and meta-analysis showed that HIK1083 has moderate overall diagnostic accuracy as a marker of GTAC, with high specificity and low sensitivity. MUC6 showed low accuracy instead.
The MUC6 gene, which encodes for gastrin mucin protein MUC6, has been described in 1993 in the USA [19]. MUC6 expression has also been described in biliary epithelium in a subset of neoplasms of the breast [20], [21]. HIK1083 is a mouse monoclonal antibody developed in Japan in the ‘90 s. HIK1083
CONCLUSIONBoth HIK1083 and MUC6 show low sensitivity as diagnostic markers of GTAC. However, HIK1083 shows high specificity and moderate overall accuracy, while MUC6 shows moderate specificity and low overall accuracy. An integrate approach including histology, immunohistochemistry and, if necessary, in situ hybridization appears crucial for a correct diagnosis of GTAC and an appropriate patient management.
Conflict of interestThe authors declare no conflict of interest.
REFERENCES (26)B. Vandenhaute et al.Mucin gene expression in biliary epithelial cellsJ Hepatol
(1997 Dec)
N.W. Toribara et al.Human gastric mucinIdentification of a unique species by expression cloning. J Biol Chem
(1993 Mar 15)
F. Bray et al.Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countriesCA Cancer J. Clin
(2018)
WHO Classification of Tumours Editorial Board. Female genital tumours. Lyon (France): International Agency for Research...P. Cattani et al.RNA (E6 and E7) assays versus DNA (E6 and E7) assays for risk evaluation for women infected with human papillomavirusJ Clin Microbiol
(2009 Jul)
A. Kojima et al.Gastric morphology and immunophenotype predict poor outcome in mucinous adenocarcinoma of the uterine cervixAm J Surg Pathol
(2007 May)
K.J. Park et al.Unusual endocervical adenocarcinomas: an immunohistochemical analysis with molecular detection of human papillomavirusAm J Surg Pathol
(2011 May)
T. Wada et al.Endocervical Adenocarcinoma With Morphologic Features of Both Usual and Gastric Types: Clinicopathologic and Immunohistochemical Analyses and High-risk HPV Detection by In Situ HybridizationAm J Surg Pathol
(2017 May)
S. Asaka et al.Trefoil factor family 2 protein: a potential immunohistochemical marker for aiding diagnosis of lobular endocervical glandular hyperplasia and gastric-type adenocarcinoma of the uterine cervixVirchows Arch
(2019 Jan)
A. Nakamura et al.Mucinous adenocarcinoma, gastric type of the uterine cervix: clinical features and HER2 amplificationMed Mol Morphol
(2019 Mar)
S. Stolnicu et al.Diagnostic Algorithmic Proposal Based on Comprehensive Immunohistochemical Evaluation of 297 Invasive Endocervical AdenocarcinomasAm J Surg Pathol
(2018 Aug)
K. Takako et al.Trefoil Factor 2 (TFF2) as a Surrogate Marker for Endocervical Gastric-type CarcinomaInt J Gynecol Pathol
(2021 Jan)
A. Raffone et al.PAX2 in endometrial carcinogenesis and in differential diagnosis of endometrial hyperplasia: A systematic review and meta-analysis of diagnostic accuracyActa Obstet Gynecol Scand
(2019 Mar)
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