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Impact of Intratumoral Nerve Growth Factor Expression on Perineural Invasion and Prognosis in Resectable Extrahepatic Cholangiocarcinoma
Kazuhide Urabe*1, Yoshiaki Murakami1, Kenichiro Uemura1, Yasushi Hashimoto1, Naru Kondo1, Naoya Nakagawa1, Hayato Sasaki1, Eiso Hiyama2, Taijiro Sueda1
1Department of Surgery, Applied Life Sciences Institute of Biomedical & Health Sciences, Hiroshima University, Hiroshima-city, Japan; 2Natural Science Center for Basic Research and Development, Hiroshima university, Hiroshima-City, Japan
Background
Perineural invasion is one of the risk factors of poor survival in extrahepatic cholangiocarcinoma. Intratumoral expression of nerve growth factor (NGF), which is a crucial neurotrophic factor of nerve growth and proliferation in proto neural crest, has been reported to be associated with perineural invasion in several kinds of cancers. However, it is still unclear whether intratumoral NGF expression impacts on perineural invasion and survival in extrahepatic cholangiocarcinoma. The aim of this study was to investigate the association of NGF expression in resected specimens with perineural invasion and survival of patients who underwent surgical resection for extrahepatic cholangiocarcinoma.
Materials and Methods
Records of 112 patients with extrahepatic cholangiocarcinoma (including 53 with distal cholangiocarcinoma and 59 with perihilar cholangiocarcinoma) who underwent surgical resection between September 1999 and April 2014 were reviewed retrospectively. Intratumoral NGF expression were investigated using immunohistochemical technique. Relationships between NGF expression and clinicopathological factors including perineural invasion in resected specimen were statistically evaluated, and risk factors for poor survival of patients with resectable extrahepatic cholangiocarcinoma were analyzed using univariate and multivariate analyses.
Results
High and low intratumoral NGF expression was observed in 62 (55%) and 50 (45%) patients, respectively. For all 112 patients, no significant differences was found between NGF expression and presence of perineural invasion (P = 0.94). Moreover, intratumoral NGF expression was not associated overall survival (P = 0.97). In multivariate analysis, presence of perineural invasion (hazard ratio [HR] 3.53: 95% confidence interval [CI] 1.52-10.3; P = 0.0021) and lymph node metastasis (HR 2.47; 95% CI 1.56-5.08; P = 0.0005) are identified significant as independent risk factors for poor overall survival.
Conclusion
The current results suggested that presence of perineural invasion in extrahepatic cholangiocarcinoma was an independent risk factor of poor survival of patients with resectable extrahepatic cholangiocarcinoma, however, NGF expression was probably not associated with perineural invasion, and did not impact on their survival.
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