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

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

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)899-906
Number of pages8
JournalAnnals of Surgical Oncology
Volume26
Issue number3
DOIs
Publication statusPublished - Mar 15 2019

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Drug Therapy
Neoplasms
Multivariate Analysis
Immunohistochemistry
Esophageal Squamous Cell Carcinoma
Confidence Intervals
Cell Line
Survival
Therapeutics

All Science Journal Classification (ASJC) codes

  • Surgery
  • Oncology

Cite this

Hara, T., Makino, T., Yamasaki, M., Tanaka, K., Miyazaki, Y., Takahashi, T., ... Doki, Y. (2019). Effect of c-Met and CD44v6 Expression in Resistance to Chemotherapy in Esophageal Squamous Cell Carcinoma. Annals of Surgical Oncology, 26(3), 899-906. https://doi.org/10.1245/s10434-018-07126-5

Effect of c-Met and CD44v6 Expression in Resistance to Chemotherapy in Esophageal Squamous Cell Carcinoma. / Hara, Takeo; Makino, Tomoki; Yamasaki, Makoto; Tanaka, Koji; Miyazaki, Yasuhiro; Takahashi, Tsuyoshi; Kurokawa, Yukinori; Nakajima, Kiyokazu; Matsuura, Nariaki; Mori, Masaki; Doki, Yuichiro.

In: Annals of Surgical Oncology, Vol. 26, No. 3, 15.03.2019, p. 899-906.

Research output: Contribution to journalArticle

Hara, T, Makino, T, Yamasaki, M, Tanaka, K, Miyazaki, Y, Takahashi, T, Kurokawa, Y, Nakajima, K, Matsuura, N, Mori, M & Doki, Y 2019, 'Effect of c-Met and CD44v6 Expression in Resistance to Chemotherapy in Esophageal Squamous Cell Carcinoma', Annals of Surgical Oncology, vol. 26, no. 3, pp. 899-906. https://doi.org/10.1245/s10434-018-07126-5
Hara, Takeo ; Makino, Tomoki ; Yamasaki, Makoto ; Tanaka, Koji ; Miyazaki, Yasuhiro ; Takahashi, Tsuyoshi ; Kurokawa, Yukinori ; Nakajima, Kiyokazu ; Matsuura, Nariaki ; Mori, Masaki ; Doki, Yuichiro. / Effect of c-Met and CD44v6 Expression in Resistance to Chemotherapy in Esophageal Squamous Cell Carcinoma. In: Annals of Surgical Oncology. 2019 ; Vol. 26, No. 3. pp. 899-906.
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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.",
author = "Takeo Hara and Tomoki Makino and Makoto Yamasaki and Koji Tanaka and Yasuhiro Miyazaki and Tsuyoshi Takahashi and Yukinori Kurokawa and Kiyokazu Nakajima and Nariaki Matsuura and Masaki Mori and Yuichiro Doki",
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T1 - Effect of c-Met and CD44v6 Expression in Resistance to Chemotherapy in Esophageal Squamous Cell Carcinoma

AU - Hara, Takeo

AU - Makino, Tomoki

AU - Yamasaki, Makoto

AU - Tanaka, Koji

AU - Miyazaki, Yasuhiro

AU - Takahashi, Tsuyoshi

AU - Kurokawa, Yukinori

AU - Nakajima, Kiyokazu

AU - Matsuura, Nariaki

AU - Mori, Masaki

AU - Doki, Yuichiro

PY - 2019/3/15

Y1 - 2019/3/15

N2 - 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.

AB - 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.

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