Gastric Morphology and Immunophenotype Predict Poor Outcome in Mucinous Adenocarcinoma of the Uterine Cervix

Abstract

Endocervical-type mucinous adenocarcinoma (ECA) of the uterine cervix is defined as a tumor composed of cells resembling those of the endocervical glands, but recent studies have demonstrated that a minority of ECAs displays a gastric immunophenotype. The aim of this study was to assess the significance of the gastric phenotype. Fifty-three cases of mucinous adenocarcinoma of the uterine cervix (37 FIGO stage IB, 4 stage IIA, and 12 stage IIB) were reviewed and reevaluated using a newly established morphologic criteria for distinguishing gastric type adenocarcinoma, which was defined as a tumor showing clear and/or pale eosinophilic and voluminous cytoplasm, with distinct cell borders. The results were correlated with gastric immunophenotype, determined by HIK1083 and MUC6 immunostaining, and patient outcome. Following the current World Health Organization scheme (2003), 47 tumors (89%) were classified as ECA, 1 (2%) as intestinal type, 1 (2%) as mixed endocervical and intestinal type, and 4 (8%) as minimal deviation adenocarcinoma. Twelve of 47 (26%) ECAs and all 4 minimal deviation adenocarcinomas, reclassified as gastric type using the novel criteria, were frequently positive for HIK1083 with a rate of 75% (12/16), whereas only 11% (4/37) of nongastric tumors were positive. There was no significant difference in MUC6 reactivity between gastric and nongastric type tumors (31%, 5/16 vs. 16%, 6/37; P=0.4). Patients with gastric-type adenocarcinomas had a significantly decreased 5-year disease-specific survival rate (30 vs. 77%; P<0.0001), and the gastric type morphology was related to a significant risk for disease recurrence compared with the nongastric type (P=0.001; HR, 4.5; 95% confidence interval, 1.42-14.2). HIK1083-positivity was also related to decreased 5-year disease-specific survival rate (38% vs. 74%; P<0.005). Mucinous adenocarcinoma of the uterine cervix with gastric immunophenotype can be a distinct morphologic variant showing an aggressive clinical course.

Absence of High-Risk Human Papillomavirus (HPV) Detection in Endocervical Adenocarcinoma with Gastric Morphology and Phenotype

“…In a previous investigation we demonstrated that mucinous AC with gastric immunophenotype was morphologically distinct with a good interobserver reproducibility, characterized by neoplastic cells with conspicuous cell borders and clear and/or pale eosinophilic voluminous cytoplasm, and aggressive clinical behavior. 20,23 MDA is not a common neoplasm, accounting for 1-3% of all endocervical ACs, but the gastric-type adenocarcinoma (GAC) appears in 10 -30% of all endocervical ACs 19,20 and thus may not be a negligible pitfall of HPV DNA tests and vaccination, and therapeutic strategy.…”

“…19,20 Additionally, both neoplasms can be associated with lobular endocervical glandular hyperplasia (LEGH), 19 which represents a pyloric gland metaplasia 21 and has also been shown to be hr-HPV DNA-negative. 16,22 These facts suggest that the mucinous AC with gastric immunophenotype, incorporating MDA as its well-differentiated form in the morphological spectrum, is a distinct entity arising via a hr-HPV-independent pathway.…”

Synchronous cervical minimal deviation adenocarcinoma, gastric type adenocarcinoma and lobular endocervical glandular hyperplasia along with stil in peutz-jeghers syndrome: eliciting oncogenesis pathways

“…The 5-year disease-free survival rate of patients with gastric-type adenocarcinoma (38%) was substantially lower than that of patients with the usual type of uterine cervical adenocarcinoma (74%). In the study by kojima et al, gastric morphology and immunophenotype (HIk1083-positivity) were found to be independent predictive factors of disease recurrence and decreased survival in stage I and II cervical adenocarcinoma (17). The minimal deviation adenocarcinoma also has a less favorable prognosis than the usual type of endocervical adenocarcinoma.…”

Magnetic resonance imaging findings and prognosis of gastric-type mucinous adenocarcinoma (minimal deviation adenocarcinoma or adenoma malignum) of the uterine corpus: Two case reports

“…The immunophenotype of these neoplasms is characterized by positivity for HIK1083 and/or MUC6, partial positivity for p53, and negativity for p16 (5). This type of adenocarcinoma of the uterine cervix is considered to be associated with poor prognosis due to its more aggressive clinical behavior compared with the usual types of adenocarcinoma of the uterine cervix (6,8). However, among mucinous adenocarcinomas of the uterine corpus, only two cases displaying the gastric phenotype have been previously reported in the English literature (3,4).…”

“…Watery discharge is a major symptom of gastric-type adenocarcinoma of the uterine cervix, and macroscopic examination has revealed small cysts associated with the tumor. Although gastric-type mucinous adenocarcinoma of the uterine cervix exhibits a benign histological appearance, it is typically associated with chemoresistance and poor prognosis (6).…”