Clinicopathological Features and Prognostic Significance of CLDN18 in Gastric-Type Endocervical Adenocarcinoma: A Study of 13 Patients-A Single Institution Experience.

Abstract

ObjectiveGastric-type endocervical adenocarcinoma (G-EAC) is a rare, non-HPV-associated subtype of endocervical adenocarcinoma with challenging diagnosis and poor prognosis. This study aims to characterize its clinicopathological features and evaluate the expression and prognostic significance of CLDN18.MethodsA total of 13 patients with pathologically confirmed G-EAC were collected.ResultsThe 13 patients, aged 39 to 64 years (mean 51.6 years), mostly sought medical attention due to abnormal findings on physical examination or specific symptoms, including abnormal vaginal discharge. Ten specimens were well-differentiated G-EAC, and 3 were moderately to poorly differentiated G-EAC. Atypical lobular endocervical gland hyperplasia (LEGH) was observed adjacent to G-EAC in 12 specimens. The International Federation of Gynecology and Obstetrics (FIGO) stage was stage I in 12 specimens and stage III in 1 specimen. The Ki-67 proliferation index ranged from <5% to 90%. Mutant-type immunostaining of p53 (overexpression or null pattern) was observed in 9 specimens; all 13 specimens were negative for estrogen receptor (ER), and 7 specimens showed positive CLDN18 expression. An exploratory survival analysis showed a trend toward shorter progression-free survival (PFS) in patients with positive CLDN18 expression (P = .044), a finding limited by the small sample size. Thus, CLDN18 may serve as a highly specific diagnostic adjunct in a panel, and its potential prognostic significance warrants further investigation in larger cohorts.ConclusionG-EAC is rare, and its clinical diagnosis is challenging. Clinicians should maintain a high index of suspicion, perform colposcopy with multi-site biopsy and endocervical curettage for suspicious specimens. Pathologists should integrate a panel of immunohistochemical markers with morphology to differentiate it from benign mimics. In addition, CLDN18 may not only serve as a diagnostic marker for G-EAC but may also be associated with patient prognosis, demonstrating its potential predictive value.