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

INTRODUCTION: 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.

Immunohistochemical expression of HIK1083 and MUC6 in endometrial carcinomas.

AIMS: Gastric-type endocervical adenocarcinoma (EA) is characterised by aggressive behaviour and pathogenesis independent of human papillomavirus infection. Because of its morphology and frequent mutation-pattern expression of p53, gastric-type EA may be confused with several types of endometrial carcinoma, particularly in biopsy and curettage specimens. HIK1083 and MUC6 are immunohistochemical markers used to support a diagnosis of gastric-type EA; however, the rates of expression of these markers in endometrial tumours are largely unknown. We therefore aimed to assess the expression of HIK1083 and MUC6 in a cohort of different types of endometrial carcinoma. METHODS AND RESULTS: Ninety-one endometrial carcinomas (56 endometrioid, 16 clear cell, and 19 serous) from 91 patients treated with hysterectomy were included. A representative tumour block from each case was used for immunohistochemical staining with HIK1083 and MUC6. The percentage of stained cells (0-100%) and average staining intensity (weak, moderate, and strong) were recorded for both markers. None of 91 cases expressed HIK1083. In contrast, 66% (60/91) of cases showed at least focal expression of MUC6; importantly, 54 of 60 (90%) positive cases showed moderate or strong staining. Five of 60 (8%) cases showed MUC6 staining in ≥50% of tumour cells. Endometrioid tumours (49/56, 88%) were more likely to express MUC6 than cases of clear cell (1/16, 6%) or serous (10/19, 53%) carcinoma. DISCUSSION: Endometrial carcinoma often expresses MUC6. In contrast, HIK1083 is consistently negative, and thus, when positive, is a more reliable marker for distinguishing gastric-type EA from some of its endometrial mimics.

Gastric-type adenocarcinoma in situ of uterine cervix: cytological and histopathological features of two cases.

Benign, premalignant, and malignant endocervical glandular lesions occasionally show a gastric phenotype. We report 2 cases of gastric-type adenocarcinoma in situ (AIS) of the endocervix, not associated with lobular endocervical glandular hyperplasia or gastric-type adenocarcinoma. Cytologically, both showed endocervical glands with slightly enlarged nuclei, distinctive nucleoli, pseudostratified strips, and intracytoplasmic golden yellow mucin. Histologically, both lesions were situated in preexisting endocervical glands and presented columnar cells with voluminous pale eosinophilic cytoplasm and evident nuclear atypia. In case 1, the lesion was located at the mid-zone of the endocervical canal and, in case 2, at the outer endocervical canal with extension to the transformation zone and prominent intestinal metaplasia. In both, the cells showed voluminous cytoplasm containing gastric-type mucin, stained red by combined alcian blue/periodic acid-Schiff stain. Immunohistochemically, both lesions were positive for HIK1083 and p53, while negative for p16 and ER. Human papilloma virus (HPV) DNA was not detected by polymerase chain reaction. Our cases illustrate that gastric-type AIS can occur without lobular endocervical glandular hyperplasia. The lesions can occur in the outer cervical canal and present extensive intestinal differentiation. Awareness of this rare type of endocervical glandular lesion is important since they are pathogenetically different from the more common HPV-associated lesions and may become more prevalent in the HPV-eradicating era.