A Start on the Development of Near-infrared Fluorescence Imaging of Hilar Cholangiocarcinoma.

Matton, A. (Alix) (2013) A Start on the Development of Near-infrared Fluorescence Imaging of Hilar Cholangiocarcinoma. thesis, Medicine.

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Abstract

Cholangiocarcinoma (CCA) is an aggressive cancer arising from the biliary epithelial cells. The hilar type, which occurs at the confluence of the right and left hepatic ducts, is the most common type and carries the worst prognosis. The only potentially curative treatment is surgery, and even then the 5-year survival rate is only 11-40%. Obtaining tumor negative resection margins during surgery increases the survival, though this can often not be achieved. This is due to the invasive growth characteristics of hilar CCA, with perineural- and angio-invasion, and extensive desmoplastic reactions that form around the tumor. A technique that would help surgeons in locating the tumor and obtaining tumor negative margins would be intraoperative near-infrared fluorescence (NIRF) imaging. This is a rapidly developing technique and involves the use of specifically targeted markers attached to a fluorophore, which subsequently make the tumor fluoresce under near-infrared light. This study made a start on the development of NIRF imaging in hilar CCA by searching the literature for potential markers and testing the expression of four of these (EGFR, CEA, Her2 and MUC1) in 29 resected cases of hilar CCA by means of immunohistochemistry. EGFR, CEA, Her2 and MUC1 expression in the tumors were 62% (mostly weak), 0%, 24% (mostly weak), and MUC1 (mostly strong), respectively. EGFR expression was also found in the stroma (17%, mostly weak) and in the liver parenchyma (100%, mostly strong), CEA in none of the surrounding tissue, Her2 in the stroma (7%, weak) and liver parenchyma (25%, weak), and MUC1 in the stroma (3%, weak) and none in the liver parenchyma. MUC1 also stained healthy bile ducts in 92% (mostly weak) of cases. MUC1 appears to be our most promising target for NIRF imaging given the very high and mostly strong expression rate of MUC1 in hilar CCA tumors, with no to low expression in non-cancerous surrounding tissue. Furthermore, MUC1 is an apical surface protein that has been successfully imaged in vivo in the past. If further research supports the potential value of MUC1 as a target, it would benefit from the availability of an already clinically approved anti-MUC1 antibody (pemtumomab).

Item Type:	Thesis (Thesis)
Supervisor name:	Porte, Prof. Dr. Robert J. and Mantel, Dr. Henk-Jan
Faculty:	Medical Sciences
Date Deposited:	25 Jun 2020 10:57
Last Modified:	25 Jun 2020 10:57
URI:	https://umcg.studenttheses.ub.rug.nl/id/eprint/1767

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