Evaluation of the serotonin pathway as a biomarker in cholangiocarcinoma

评估血清素通路作为胆管癌生物标志物的作用

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作者:Christos Fountzilas, Sylvia Alarcon Velasco, Wiam Bshara, Charles M LeVea, Medhavi Gupta, Wenyan Ji, Anthony George, Kristopher Attwood, Renuka V Iyer

Background

Cholangiocarcinomas (CCAs) are rare and aggressive malignant tumors of the biliary tract. Serotonin (5HT) has tumor-promoting effects in CCA while inhibition of 5HT synthesis can decrease tumor growth.

Conclusions

Tumor TPH-1 expression was not predictive of response to treatment. There was a trend for improved long-term outcomes in patients with high tumor TPH expression and lower serum 5HT concentration.

Methods

In this retrospective study, we evaluated the expression of 5HT and tryptophane hydroxylase-1 (TPH-1) in tumor specimens from patients treated with cisplatin plus gemcitabine (CisGem). We included consecutive patients ≥18 years, with locally advanced unresectable, recurrent, or metastatic CCA who were treated with CisGem and had available archival tumor tissue for immunohistochemistry. Formalin-fixed paraffin (FFPE) sections were stained for 5HT and TPH-1. Specimens were evaluated for neuroendocrine features and tumor-infiltrating lymphocytes (TILs). Serum 5HT was measured.

Results

We identified 23 patients fulfilling the inclusion criteria. 5HT expression was absent in almost all tumors examined. TPH-1 expression was neither associated with stage or primary tumor location nor predictive of response to CisGem. There was a trend for improved overall survival (OS) in patients whose tumors had high TPH-1 expression. The examined tumor specimens had no neuroendocrine features. Most sections had no TILs. There was a trend for worse OS in patients with high serum 5HT concentration. Conclusions: Tumor TPH-1 expression was not predictive of response to treatment. There was a trend for improved long-term outcomes in patients with high tumor TPH expression and lower serum 5HT concentration.

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