Annals of Surgical Oncology

, Volume 26, Issue 5, pp 1544–1551 | Cite as

The Significance of CD44 Variant 9 in Resected Lung Adenocarcinoma: Correlation with Pathological Early-Stage and EGFR Mutation

  • Takaki Akamine
  • Tetsuzo TagawaEmail author
  • Kayo Ijichi
  • Gouji Toyokawa
  • Shinkichi Takamori
  • Fumihiko Hirai
  • Tatsuro Okamoto
  • Yoshinao Oda
  • Yoshihiko Maehara
Translational Research and Biomarkers



CD44 isoforms serve as a marker for cancer stem cells. CD44 variant 9 (CD44v9) contributes to the defense against reactive oxygen species, resulting in resistance to chemoradiotherapy. However, the significance of CD44v9 in patients with lung adenocarcinoma is unknown.


We used immunohistochemical analysis to retrospectively analyze CD44v9 expression in 268 surgically resected lung adenocarcinomas and investigated the association between CD44v9 expression and patients’ clinicopathological features.


The expression of CD44v9 in 193 of 268 (72.0%) patients was significantly associated with early-stage cancer, low-grade tumors, absence of vessel and pleural invasion, and a mutated epidermal growth factor receptor (EGFR) gene. Multivariate logistic analysis revealed that CD44v9 expression was significantly associated with early-stage disease [odds ratio (OR) 0.29, 95% confidence interval (CI) 0.14–0.59; p < 0.001] and mutant EGFR (OR 2.53, 95% CI 1.06–6.04; p = 0.036). The percentage of CD44v9-positive tumors was higher in the earlier stages of disease; however, there was no significant difference in the survival of patients in each stage of disease who had positive or negative CD44v9 expression.


CD44v9 was highly expressed in EGFR-mutant tumors, particularly in early-stage lung adenocarcinoma, suggesting that CD44v9 expression may play an important role in EGFR-mutant tumors.



The authors thank Edanz Group ( for editing a draft of this manuscript.


This research did not receive any specific grants from funding agencies in the public, commercial, or not-for-profit sectors.



Supplementary material

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Supplementary material 1 (DOCX 16 kb)
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Supplementary material 2 (DOCX 12 kb)
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Supplementary material 3 (DOCX 14 kb)
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Fig. 1 Expression of CD44 in lung adenocarcinoma demonstrating representative (a) negative and (b) positive cases (TIFF 480 kb)
10434_2018_7137_MOESM5_ESM.tif (69 kb)
Fig. 2 Mosaic plot of data for a proportion of CD44v9 Allred scores at each stage (TIFF 70 kb)
10434_2018_7137_MOESM6_ESM.tif (94 kb)
Fig. 3 Kaplan–Meier analysis of association of stage-specific CD44v9 expression in relation to progression-free and overall survival (TIFF 94 kb)


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Copyright information

© Society of Surgical Oncology 2019

Authors and Affiliations

  • Takaki Akamine
    • 1
  • Tetsuzo Tagawa
    • 1
    Email author
  • Kayo Ijichi
    • 2
  • Gouji Toyokawa
    • 1
  • Shinkichi Takamori
    • 1
  • Fumihiko Hirai
    • 1
  • Tatsuro Okamoto
    • 1
  • Yoshinao Oda
    • 3
  • Yoshihiko Maehara
    • 1
  1. 1.Department of Surgery and Science, Graduate School of Medical SciencesKyushu UniversityFukuoka-shiJapan
  2. 2.Pathophysiological and Experimental Pathology, Department of Pathology, Graduate School of Medical SciencesKyushu UniversityFukuoka-shiJapan
  3. 3.Department of Anatomic Pathology, Graduate School of Medical SciencesKyushu UniversityFukuoka-shiJapan

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