Publication: AHNAK2 is a novel diagnostic biomarker for gallbladder adenocarcinoma
Authors
Qi Song ; Lei Xu ; Xinyi Zhang ; Minying Deng ; Jie Huang ; Jieakesu Su ; Huimei Wang ; Yingyong Hou ; Lingli Chen
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Publisher
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Universidad de Murcia, Departamento de Biologia Celular e Histiologia
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DOI
https://doi.org/10.14670/HH-25-032
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info:eu-repo/semantics/article
Description
Abstract
Objective. To investigate the pathological
diagnostic value of AHNAK2 in gallbladder carcinoma
(GBC), especially in adenocarcinoma (AC).
Methods. Tissue microarrays (TMAs) were
constructed from 296 gallbladder tumor cases,
comprising 562 cores that included normal/atypical
epithelium, low-grade intraepithelial neoplasia (LGIN),
high-grade intraepithelial neoplasia/carcinoma in situ
(HGIN/TIS), and GBC. Immunohistochemical staining
for AHNAK2 and IMP3 was performed on these TMAs
and another 10 GBC cases, and the sensitivity and
specificity of AHNAK2 were assessed across different
gallbladder tumor types.
Results. AHNAK2 immunohistochemical expression
demonstrated a progressive increase across pathological
stages (p<0.001). Among tumor types, AHNAK2
positivity was observed in 67.53% (260/385) of ACs,
97.83% (45/46) of adenosquamous/squamous cell
carcinomas (ASC/SCCs), 34.78% (8/23) of neuro
endocrine carcinomas/mixed neuroendocrine-non
neuroendocrine neoplasms (NEC/miNEN), but not in
areas of NECs, and none in undifferentiated carcinomas
(UCs). Importantly, among three grades of well,
moderately, and poorly differentiated AC, the positive
rate of AHNAK2 decreased from 70.59% (24/34),
70.11% (190/271), to 57.50% (46/80); conversely, IMP3
increased from 58.82%, 78.97% to 83.75%. Given the
extremely low positivity rates of AHNAK2 and IMP3 in
normal/atypical epithelium, combining these markers
significantly improved diagnostic performance,
demonstrating 83.73% sensitivity and 91.38% specificity
for HGIN/TIS and GBC, achieving sensitivities of
91.18%, 90.77%, and 93.75% across well, moderately,
and poorly differentiated ACs.
Conclusion. AHNAK2 demonstrates moderate
sensitivity and high specificity in the pathological diagnosis of GBC, particularly for well-differentiated
ACs. Combining AHNAK2 with IMP3 significantly
enhances diagnostic sensitivity, achieving up to 90%
across all AC grades.
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