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Reduced nuclear and ectopic cytoplasmic expression of lysyl oxidase–like 2 is associated with lymph node metastasis and poor prognosis in esophageal squamous cell carcinoma☆

  • Tian-Yu Li, PhD

      Affiliations

    • Department of Biochemistry and Molecular Biology, Medical College of Shantou University, Shantou 515041, China
    • ,
  • Li-Yan Xu, PhD

      Affiliations

    • The Key Immunopathology Laboratory of Guangdong Province, Institute of Oncologic Pathology, Medical College of Shantou University, Shantou 515041, China
    • ,
  • Zhi-Yong Wu, MD

      Affiliations

    • Department of Oncologic Surgery, Shantou Central Hospital, Affiliated Shantou Hospital of Sun Yat-sen University, Shantou 515041, China
    • ,
  • Lian-Di Liao, BS

      Affiliations

    • The Key Immunopathology Laboratory of Guangdong Province, Institute of Oncologic Pathology, Medical College of Shantou University, Shantou 515041, China
    • ,
  • Jin-Hui Shen, MD

      Affiliations

    • Department of Pathology, Shantou Central Hospital, Affiliated Shantou Hospital of Sun Yat-sen University, Shantou 515041, China
    • ,
  • Xiu-E Xu, BS

      Affiliations

    • The Key Immunopathology Laboratory of Guangdong Province, Institute of Oncologic Pathology, Medical College of Shantou University, Shantou 515041, China
    • ,
  • Ze-Peng Du, PhD

      Affiliations

    • The Key Immunopathology Laboratory of Guangdong Province, Institute of Oncologic Pathology, Medical College of Shantou University, Shantou 515041, China
    • ,
  • Qing Zhao, MS

      Affiliations

    • The Key Immunopathology Laboratory of Guangdong Province, Institute of Oncologic Pathology, Medical College of Shantou University, Shantou 515041, China
    • ,
  • En-Min Li, PhD

      Affiliations

    • Department of Biochemistry and Molecular Biology, Medical College of Shantou University, Shantou 515041, China
    • Corresponding Author InformationCorresponding authors. En-Min Li is to be contacted at Department of Biochemistry and Molecular Biology, Medical College of Shantou University, Shantou 515041, China. Li-Yan Xu, Institute of Oncologic Pathology, Medical College of Shantou University, No.22, Xinling Road, Shantou 515041, Guangdong, China.

Received 28 April 2011; received in revised form 8 July 2011; accepted 22 July 2011. published online 28 December 2011.
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Summary 

Lysyl oxidase family members have various roles in cancer progression. The aim of this study was to investigate their expression and clinical significance in esophageal squamous cell carcinoma. We examined messenger RNA expression of lysyl oxidase family members including lysyl oxidase and lysyl oxidase–like proteins (lysyl oxidase L) in 10 esophageal squamous cell carcinoma cell lines and 83 pairs of tumor samples by quantitative real-time polymerase chain reaction. All except lysyl oxidase L3 were expressed at high levels in esophageal squamous cell carcinoma, but only lysyl oxidase L2 was associated with lymph node metastasis (P = .034). We examined lysyl oxidase L2 protein further by immunohistochemistry staining in 178 surgically resected esophageal squamous cell carcinoma tissue samples. The protein manifested decreased nuclear expression and increased cytoplasmic expression. Moreover, these 2 events both had significant correlation with the presence of lymph node metastasis (P = .001 and P < .001). Overall survival rates of the patients with esophageal squamous cell carcinoma with decreased nuclear expression or increased cytoplasmic expression of lysyl oxidase L2 were significantly lower than those of the patients with esophageal squamous cell carcinoma with the reverse expression pattern (P = .040 or P = .022). Multivariate analyses revealed that nuclear expression of lysyl oxidase L2 was an independent prognostic factor for esophageal squamous cell carcinoma. These results suggest that lysyl oxidase L2 exerts a critical effect on esophageal squamous cell carcinoma progression and can be a predictive marker of lymph node metastasis and outcome.

Keywords: Esophageal squamous cell carcinoma, Lysyl oxidase–like 2, Prognostic factors

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☆ This work was supported by grants from the National Nature Science Foundation of China (No. 81000900; Beijing, China) and the National Natural Science Foundation of China-Guangdong Joint Fund (No. U0932001; Beijing, China).

PII: S0046-8177(11)00370-4

doi:10.1016/j.humpath.2011.07.027

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