Annals of Surgical Oncology

, Volume 26, Issue 3, pp 899–906 | Cite as

Effect of c-Met and CD44v6 Expression in Resistance to Chemotherapy in Esophageal Squamous Cell Carcinoma

  • Takeo Hara
  • Tomoki MakinoEmail author
  • Makoto Yamasaki
  • Koji Tanaka
  • Yasuhiro Miyazaki
  • Tsuyoshi Takahashi
  • Yukinori Kurokawa
  • Kiyokazu Nakajima
  • Nariaki Matsuura
  • Masaki Mori
  • Yuichiro Doki



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.


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.


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.


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.


Author Contributions

TH, TM, MY, MM, and YD: conception, design of the study; TH, TM, MY, KT, and YD: surgery and acquisition of clinical data; TH: immunohistochemical staining; TH, TM, and NM: evaluation of immunohistochemical staining; TH, TM, YM, TT, YK, and KN: analysis of data; TH: drafting the article; TM: critical revision of the article; MM and YD: final approval of the article.

Supplementary material

10434_2018_7126_MOESM1_ESM.tif (193 kb)
Supplemental Fig. S1 Kaplan-Meier survival analysis of overall survival among patients who (a) did not receive preoperative therapy classified by c-Met expression, (b) did not receive preoperative therapy classified by CD44v6 expression, (c) did not receive preoperative therapy classified by c-Met and CD44v6 expression, (d) received preoperative chemotherapy classified by c-Met expression, (e) received preoperative chemotherapy classified by CD44v6 expression, and (f) received preoperative chemotherapy classified by c-Met and CD44v6 expression (TIFF 193 kb)
10434_2018_7126_MOESM2_ESM.tif (154 kb)
Supplemental Fig. S2 Kaplan-Meier survival analysis of overall survival according to c-Met/CD44v6 expression in (a) pT1-2 group, (b) pN0 group, (c) pT3-4 group, (d) pN1-3 group (TIFF 154 kb)


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Copyright information

© Society of Surgical Oncology 2019

Authors and Affiliations

  • Takeo Hara
    • 1
  • Tomoki Makino
    • 1
    Email author
  • Makoto Yamasaki
    • 1
  • Koji Tanaka
    • 1
  • Yasuhiro Miyazaki
    • 1
  • Tsuyoshi Takahashi
    • 1
  • Yukinori Kurokawa
    • 1
  • Kiyokazu Nakajima
    • 1
  • Nariaki Matsuura
    • 2
    • 3
  • Masaki Mori
    • 1
  • Yuichiro Doki
    • 1
  1. 1.Department of Gastroenterological SurgeryOsaka University, Graduate School of MedicineSuita CityJapan
  2. 2.Osaka International Cancer InstituteOsakaJapan
  3. 3.Department of Molecular PathologyOsaka University Graduate School of Medicine, Division of Health SciencesSuita CityJapan

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