Diagnostic accuracy of HIK1083 and MUC6 as immunohistochemical markers of endocervical gastric-type adenocarcinoma: a systematic review and meta-analysis

Elsevier

Available online 5 December 2022, 154261

Pathology - Research and PracticeAuthor links open overlay panelABSTRACTIntroduction

HIK1083 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.

Methods

Three 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.

Results

Four 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%.

Conclusion

HIK1083 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 snippetsINTRODUCTION

Cervical 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 METHODS

This 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 characteristics

The 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

DISCUSSION

This 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

CONCLUSION

Both 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 interest

The authors declare no conflict of interest.

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