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. 2025 Sep 1;33(5):330-338.
doi: 10.1097/PAI.0000000000001268. Epub 2025 May 29.

Expression of Hippo Pathway Molecules in Distal Bile Duct Cancer

Ki Rim Lee  1 , Soon Auck Hong, Mineui Hong, Joo Young Kim
Affiliations

Expression of Hippo Pathway Molecules in Distal Bile Duct Cancer

Ki Rim Lee et al. Appl Immunohistochem Mol Morphol. .

Abstract

The Hippo pathway is a tumor-suppressive pathway. Hippo pathway dysregulation correlates with cancer progression, metastasis, and a poor prognosis. Large tumor suppressor homolog 1/2 (LATS1/2), Yes-associated protein (YAP), and TEA domain-containing sequence-specific transcription factor 4 (TEAD4) are primary Hippo pathway components. We evaluated LATS1/2, YAP, and TEAD4 expression and their correlation with clinicopathological behavior and prognostic significance in 67 distal bile duct cancer (DBDC) cases. LATS1/2 expression was observed in 20 (29.9%) DBDC cases and correlated significantly with low pT classification, absence of lymphovascular invasion, and low American Joint Committee on Cancer (AJCC) stage. High YAP expression was identified in 35 (52.2%) cases and correlated with high pT classification, AJCC stage, and TEAD4 expression. High TEAD4 expression was observed in 13 (19.4%) cases and correlated significantly with lymph node metastasis, involved resection margins, and high AJCC stage. Overall survival was significantly better in patients with DBDC with than in those without LATS1/2 expression ( P < 0.001), and significantly worse in patients with high than in those with low YAP and TEAD4 expression ( P = 0.014, 0.037, respectively). The overall survival of patients with combined LATS1/2 + YAP or TEAD4 low expression was significantly better than that of other groups [hazard ratio (HR) 5.809; 95% CI, 1.770-19.065; P = 0.001]. This combination was an independent good prognostic factor (HR 4.399; 95% CI, 1.313-14.743; P = 0.016) in patients with DBDC. LATS1/2, YAP, and TEAD4 expression correlates with DBDC clinicopathological behavior and may be useful prognostic markers in patients with DBDC.

Keywords: Hippo pathway; LATS1/2; TEAD4; YAP; dital bile duct cancer.

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Conflict of interest statement

The authors declare no conflict of interest.

References

    1. Klimstra D, Nagteggal I, Rugge M, et al. WHO Classification of Tumours of the Digestive System. 5th ed. International Agency for Research on Cancer; 2019.
    1. Shin HR, Oh JK, Masuyer E, et al. Comparison of incidence of intrahepatic and extrahepatic cholangiocarcinoma--focus on East and South-Eastern Asia. Asian Pac J Cancer Prev. 2010;11:1159–1166.
    1. Choi SB, Park SW, Kim KS, et al. The survival outcome and prognostic factors for middle and distal bile duct cancer following surgical resection. J Surg Oncol. 2009;99:335–342.
    1. Komaya K, Ebata T, Shirai K, et al. Recurrence after resection with curative intent for distal cholangiocarcinoma. Br J Surg. 2017;104:426–433.
    1. Zhou GX, Li XY, Zhang Q, et al. Effects of the hippo signaling pathway in human gastric cancer. Asian Pac J Cancer Prev. 2013;14:5199–5205.

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