Erschienen in:
04.01.2019 | TRANSLATIONAL RESEARCH AND BIOMARKERS
Effect of c-Met and CD44v6 Expression in Resistance to Chemotherapy in Esophageal Squamous Cell Carcinoma
verfasst von:
Takeo Hara, MD, Tomoki Makino, MD, PhD, Makoto Yamasaki, MD, PhD, Koji Tanaka, MD, PhD, Yasuhiro Miyazaki, MD, PhD, Tsuyoshi Takahashi, MD, PhD, Yukinori Kurokawa, MD, PhD, Kiyokazu Nakajima, MD, PhD, Nariaki Matsuura, MD, PhD, Masaki Mori, MD, PhD, Yuichiro Doki, MD, PhD
Erschienen in:
Annals of Surgical Oncology
|
Ausgabe 3/2019
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Abstract
Background
c-Met relies on CD44v6 for its activation and signaling in several cancer cell lines. However, the correlation of c-Met and CD44v6 expression and its biological significance in esophageal squamous cell carcinoma (ESCC) remains unknown.
Methods
Expression of c-Met and CD44v6 was examined by immunohistochemistry (IHC) in 147 ESCC specimens. We analyzed the impact of c-Met and CD44v6 expression on clinicopathological parameters, including chemoresistance or prognosis in ESCC.
Results
High expression of c-Met and CD44v6 in cancerous lesions was identified in 49.7% and 50.3% of all patients, respectively. The c-Met-high group comprised more advanced pT and pM stages than the c-Met-low group. In addition, more patients in the c-Met-high group received neoadjuvant chemotherapy (NACT) than the c-Met-low group (64.4% vs. 43.2%, P = 0.010). On the other hand, the CD44v6-high group was associated with more advanced pT/pN stages and a poorer clinical response to NACT (response rate 53.5% vs. 77.8%, P = 0.025) than the CD44v6-low group. Double-positive immunostaining of c-Met and CD44v6 was identified in 28.6% of all cases, and multivariate analysis of overall survival (OS) identified them (hazard ratio 1.79, 95% confidence interval 1.03–3.04, P = 0.038) as independent prognostic factors in addition to pN and pM stage.
Conclusions
c-Met/CD44v6 were associated with tumor progression or chemoresistance. Double-positive expression of c-Met and CD44v6 negatively impacted patient prognosis in ESCC, implying that c-Met and CD44v6 are candidates for targeted therapy in ESCC.