Expression status of CD44 and CD133 as a prognostic marker in esophageal squamous cell carcinoma treated with neoadjuvant chemotherapy followed by radical esophagectomy

Okamoto,Koichi; Ninomiya,Itasu; Ohbatake,Yoshinao; Hirose,Atsushi; Tsukada,Tomoya; Nakanuma,Shinichi; Sakai,Seisho; Kinoshita,Jun; Makino,Isamu; Nakamura,Keishi; Hayashi,Hironori; Oyama,Katsunobu; Inokuchi,Masafumi; Nakagawara,Hisatoshi; Miyashita,Tomoharu; Hidehiro,Tajima; Takamura,Hiroyuki; Fushida,Sachio; Ohta,Tetsuo

doi:10.3892/or.2016.5133

Expression status of CD44 and CD133 as a prognostic marker in esophageal squamous cell carcinoma treated with neoadjuvant chemotherapy followed by radical esophagectomy

Authors:
- Koichi Okamoto
- Itasu Ninomiya
- Yoshinao Ohbatake
- Atsushi Hirose
- Tomoya Tsukada
- Shinichi Nakanuma
- Seisho Sakai
- Jun Kinoshita
- Isamu Makino
- Keishi Nakamura
- Hironori Hayashi
- Katsunobu Oyama
- Masafumi Inokuchi
- Hisatoshi Nakagawara
- Tomoharu Miyashita
- Tajima Hidehiro
- Hiroyuki Takamura
- Sachio Fushida
- Tetsuo Ohta
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Affiliations: Department of Gastroenterologic Surgery, Kanazawa University, Kanazawa, Ishikawa 920-8641, Japan
Published online on: September 28, 2016 https://doi.org/10.3892/or.2016.5133
Pages: 3333-3342

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Abstract

Cancer stem cells (CSCs) have self-renewal and pluripotency capabilities and contribute to cancer progression and chemoresistance. It has been proposed that the treatment resistance and heterogeneity of CSCs are deeply involved in the prognosis of patients with esophageal squamous cell carcinoma (ESCC). The objective of this study was to identify the influence of the expression status of the CSC markers CD44 and CD133 on chemotherapeutic efficacy and prognosis in ESCC patients who underwent radical esophagectomy after neoadjuvant chemotherapy (NAC). Endoscopically biopsied specimens taken before NAC and surgically resected specimens after NAC were immunohistochemically assessed for CD44 and CD133 expression for 47 ESCC patients who underwent NAC followed by radical esophagectomy. The correlation between CD44 and CD133 expression status and clinicopathological findings and the prognosis of ESCC patients after NAC followed by esophagectomy were analyzed. The percentages of CD44-positive cells and CD133-positive cells in specimens were increased after NAC. CD44 and CD133 expression status before NAC did not correlate with the degree of tumor progression and had no impact on the chemotherapeutic effect. However, strong expression of CD44 or CD133 and a high proportion of CD133-expressing cells before NAC were significantly associated with poorer esophageal cancer-specific survival. Patients with strong expression of CD44 or CD133 and those with a high ratio of CD133-positive tumor cells showed significantly poor prognosis regardless of the effect of chemotherapy. Multivariate analysis showed that simultaneous strong expression of CD44 and CD133 before NAC, a high rate of CD133-positive tumor cells before NAC, and primary tumor remission assessed by preoperative endoscopy were significant independent prognostic factors for ESCC. Our data indicate that CD44 and CD133 expression status prior to treatment dictates the malignant potential of ESCC and may be a novel predictor of recurrence and prognosis of ESCC patients after treatment.

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