Skip to main page content
Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2013 Jul 23;109(2):379-86.
doi: 10.1038/bjc.2013.314. Epub 2013 Jun 18.

CD44 Variant 9 Expression in Primary Early Gastric Cancer as a Predictive Marker for Recurrence

Affiliations
Free PMC article

CD44 Variant 9 Expression in Primary Early Gastric Cancer as a Predictive Marker for Recurrence

K Hirata et al. Br J Cancer. .
Free PMC article

Abstract

Background: Multiple early gastric cancers (EGCs) may develop in 6-14% of patients even after achieving curative endoscopic submucosal dissection (ESD); however, a useful biomarker for predicting recurrence is not available. The present study investigated whether the expression of CD44 variant 9 (CD44v9), a functional cancer stem cell marker, in the primary gastric cancer tissue represents an indicator of recurrence.

Methods: Eighty-eight patients who underwent ESD for EGC from 2008 to 2010 were enrolled and monitored for recurrence for 3 years. The expression levels of CD44v9 in the tissue of initial EGCs were evaluated by immunohistochemistry, and the recurrence rate was compared between CD44v9-positive and CD44v9-negative groups. The mucin phenotype and expression of microRNA-21 (miR-21) and programmed cell death protein 4 (PDCD4) were also analysed.

Results: The recurrence rate of EGC was significantly higher in the CD44v9-positive group than in the CD44v9-negative group (hazard ratio (HR), 21.8; 95% confidence interval (CI), 5.71-83.1). However, mucin phenotypes and the expression of miR-21 and PDCD4 did not predict recurrence after ESD. Meanwhile, grade of gastric atrophy was also identified as a significant marker of multiple recurrence (HR, 4.95; 95% CI, 1.30-18.8).

Conclusion: CD44 variant 9 expression represents a potential predictive marker for recurrence in EGC.

Figures

Figure 1
Figure 1
Study design. This study included 88 patients who underwent ESD for the treatment of EGCs at the Keio University Hospital between February 2008 and March 2010. Of a total of 88 ESD samples, 10 from patients who had a history of ESD and 4 from patients in whom multiple ESDs were performed simultaneously were excluded. Of the 74 initial samples in which ESD was performed, 3 from patients who had never undergone endoscopic examination after their initial ESD, 5 from patients who had gastrectomy because of a positive margin, and 1 from a patient who was treated with chemotherapy for oesophageal cancer that developed after ESD for EGC were excluded. During the follow-up period after ESD, development of multiple recurrence of EGCs were identified in 13 cases, and no recurrences were detected in the remaining 52 cases. Abbreviations: EGC=early gastric cancer; ESD=endoscopic submucosal dissection.
Figure 2
Figure 2
Histogram of CD44v9 IHC scores for all 65 EGCs. The x axis shows the CD44v9 IHC score (%) and the y axis shows the number of patients. Abbreviations: CD44v9=CD44 variant 9; EGC=early gastric cancer; IHC=immunohistochemistry.
Figure 3
Figure 3
Representative results of CD44v9 IHC in EGC. (A) CD44v9-negative EGC. (B and C) CD44v9-positive EGC. Inverse correlation between CD44v9 expression and phospho-p38MAPK detection in EGC. Abbreviations: CD44v9=CD44 variant 9; EGC=early gastric cancer; IHC=immunohistochemistry.
Figure 4
Figure 4
Kaplan–Meier curves. (A–E) Kaplan–Meier curves for recurrence-free rate of EGC.(A) CD44v9-negative (dotted line, n=52) and CD44v9-positive (solid line, n=13) groups; (B) mucin phenotype: gastric phenotype (solid line, n=17), mixed phenotype (dotted line, n=23), and intestinal phenotype (dashed line, n=25) groups; (C) miR-21 expression: miR-21-lower (dotted line, n=27) and miR-21-higher (solid line, n=34) groups; (D) PDCD4 expression: PDCD4-lower (dotted line, n=27) and PDCD4-higher (solid line, n=38) groups; (E) type of gastric atrophy: closed-type (dotted line, n=36) and open-type (solid line, n=29) groups. Abbreviations: CD44v9=CD44 variant 9; EGC=early gastric cancer; ESD=endoscopic submucosal dissection; miR-21=microRNA-21; PDCD4=programmed cell death protein 4.

Similar articles

See all similar articles

Cited by 51 articles

See all "Cited by" articles

References

    1. Chan JA, Krichevsky AM, Kosik KS. MicroRNA-21 is an antiapoptotic factor in human glioblastoma cells. Cancer Res. 2005;65 (14:6029–6033. - PubMed
    1. Chen W, Zhang X, Chu C, Cheung WL, Ng L, Lam S, Chow A, Lau T, Chen M, Li Y, Nie Y, Wong BC, Pang R. 2013Identification of CD44+ cancer stem cells in human gastric cancer Hepatogastroenterology 60(127): DOI:10.5754/hge12881. - PubMed
    1. Collins AT, Berry PA, Hyde C, Stower MJ, Maitland NJ. Prospective identification of tumorigenic prostate cancer stem cells. Cancer Res. 2005;65 (23:10946–10951. - PubMed
    1. Dalerba P, Dylla SJ, Park IK, Liu R, Wang X, Cho RW, Hoey T, Gurney A, Huang EH, Simeone DM, Shelton AA, Parmiani G, Castelli C, Clarke MF. Phenotypic characterization of human colorectal cancer stem cells. Proc Natl Acad Sci USA. 2007;104 (24:10158–10163. - PMC - PubMed
    1. Diehn M, Cho RW, Lobo NA, Kalisky T, Dorie MJ, Kulp AN, Qian D, Lam JS, Ailles LE, Wong M, Joshua B, Kaplan MJ, Wapnir I, Dirbas FM, Somlo G, Garberoglio C, Paz B, Shen J, Lau SK, Quake SR, Brown JM, Weissman IL, Clarke MF. Association of reactive oxygen species levels and radioresistance in cancer stem cells. Nature. 2009;458 (7239:780–783. - PMC - PubMed

Publication types

MeSH terms

Feedback