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

Takaki Akamine MD, Tetsuzo Tagawa MD, PhD, Kayo Ijichi MD, Gouji Toyokawa MD, PhD, Shinkichi Takamori MD, PhD, Fumihiko Hirai MD, PhD, Tatsuro Okamoto MD, PhD, Yoshinao Oda MD, PhD, Yoshihiko Maehara MD, PhD
Translational Research and Biomarkers
Volume 26, Issue 5 / May , 2019



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.

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