Human pathology · 2026
Diagnostic utility of MUC4 expression for distinguishing pancreatic ductal adenocarcinoma from extrahepatic cholangiocarcinoma and its clinicopathological significance.
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Funakoshi Saori, Shibayama Takahiro, Nakamura Hiromi, Ho Yu-Jui, Kato Kenichiro, Nagahama Kiyotaka, Shibata Tatsuhiro, Sakamoto Yoshihiro, Shibahara Junji, Hayashi Akimasa
Аннотация
AIMS: Pancreatic ductal adenocarcinoma (PDAC) and extrahepatic cholangiocarcinoma (EHCC) arise from anatomically adjacent sites and often present with overlapping clinical and pathological features; thus, accurate differentiation is challenging. Precise distinction is essential for appropriate treatment selection and prognostic assessment. The aims of this study were to identify molecular markers that facilitate the pathological differentiation of PDAC and EHCC and to evaluate their diagnostic utility.
METHODS AND RESULTS: Publicly available bulk tumor and cell-line RNA sequencing datasets were systematically compared to identify genes with differential expression between PDAC and EHCC. Candidate markers were subsequently evaluated by immunohistochemistry of surgical specimens from 87 patients who underwent pancreaticoduodenectomy for PDAC (n = 58) or EHCC (n = 29) between 2018 and 2023. Transcriptomic analysis identified MUC4 as a candidate differential marker. Immunohistochemical analysis demonstrated significantly higher MUC4 expression in PDAC than in EHCC (median H-score [range]: 108 [0-190] vs. 50 [5-170]; P = 0.019). In PDAC, elevated MUC4 expression was significantly associated with obstructive jaundice, invasion of the anterior pancreatic surface, and perineural invasion. Receiver operating characteristic curve analysis showed that MUC4 demonstrated discriminatory performance comparable to that of serum CA19-9. Notably, the diagnostic performance of MUC4 remained preserved in cases with low CA19-9 levels.
CONCLUSIONS: MUC4 expression is significantly higher in PDAC than in EHCC, and it may serve as a practical pathological biomarker for distinguishing these malignancies. Because MUC4 immunohistochemistry is readily applicable in routine pathology practice, its evaluation may provide a useful adjunct for the differential diagnosis of periampullary tumors.
METHODS AND RESULTS: Publicly available bulk tumor and cell-line RNA sequencing datasets were systematically compared to identify genes with differential expression between PDAC and EHCC. Candidate markers were subsequently evaluated by immunohistochemistry of surgical specimens from 87 patients who underwent pancreaticoduodenectomy for PDAC (n = 58) or EHCC (n = 29) between 2018 and 2023. Transcriptomic analysis identified MUC4 as a candidate differential marker. Immunohistochemical analysis demonstrated significantly higher MUC4 expression in PDAC than in EHCC (median H-score [range]: 108 [0-190] vs. 50 [5-170]; P = 0.019). In PDAC, elevated MUC4 expression was significantly associated with obstructive jaundice, invasion of the anterior pancreatic surface, and perineural invasion. Receiver operating characteristic curve analysis showed that MUC4 demonstrated discriminatory performance comparable to that of serum CA19-9. Notably, the diagnostic performance of MUC4 remained preserved in cases with low CA19-9 levels.
CONCLUSIONS: MUC4 expression is significantly higher in PDAC than in EHCC, and it may serve as a practical pathological biomarker for distinguishing these malignancies. Because MUC4 immunohistochemistry is readily applicable in routine pathology practice, its evaluation may provide a useful adjunct for the differential diagnosis of periampullary tumors.