Prognostic impact of CD44-positive cancer stem-like cells at the invasive front of gastric cancer - PubMed (original) (raw)

Prognostic impact of CD44-positive cancer stem-like cells at the invasive front of gastric cancer

Hirokazu Kodama et al. Br J Cancer. 2017.

Abstract

Background: The invasive tumour front may provide prognostic information. We examined the relationship between the presence of cancer stem cells (CSCs) at the invasive tumour front and prognosis in gastric cancer (GC).

Methods: CD44 is a CSC marker; accordingly, CD44 standard (CD44s), CD44 variant-6 (CD44v6), and CD44 variant-9 (CD44v9) expression were examined in 123 resected primary GCs and the clinical significance of CSCs at the invasive tumour front was analysed.

Results: Thirteen (10.6%), 79 (64.2%), and 47 (38.2%) GCs were CD44s-, CD44v6-, and CD44v9-positive, respectively. Patients with CD44-positive expression at the invasive tumour front had significantly poorer disease-specific survival than those with negative expression (CD44s: P<0.00001, CD44v6: P=0.013, CD44v9: P=0.0002). CD44s expression at the invasive tumour front was an independent prognostic factor in resectable GC patients (hazard ratio=3.13; 95% confidence interval, 1.09-9.01; P=0.035) and was significantly associated with peritoneal (P<0.001), lymphatic (P<0.001), and haematogenous recurrences (P=0.008). In addition, the number of CD44 isoforms expressed in cancer cells at the invasive tumour front was associated with patient prognosis. No conventional clinicopathological factors were independently associated with CD44 expression at the invasive tumour front.

Conclusions: CD44-positive cancer stem-like cells at the invasive tumour front indicate poor survival and can be a unique biological prognostic factor for GC.

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Figures

Figure 1

Figure 1

CD44s, CD44v6, and CD44v9 expression in primary GC by IHC staining. Representative images from three cases for the expression of each CD44 isoform are shown. (A and D), (B and E), and (C and F) are from the same patient. (A) Positive staining for CD44s both in whole tumour sections and at the ITF in GC with serosal exposure. (original magnification: × 40); (B) Positive staining for CD44v6 at the mucosal layer, but negative staining at the ITF of submucosal invasive GC. (C) Negative staining for CD44v9 in the surface layer, but positive staining at the ITF of muscularis propria invasive GC. (original magnification: × 40). In the high-power field, the expression of each CD44 isoform was identified along the membrane of cancer cells (D–F). (original magnification: × 200). Abbreviations: CD44s=CD44 standard isoform; CD44v6=CD44 variant isoform 6; CD44v9=CD44 variant isoform 9; GC=gastric cancer; IHC=immunohistochemistry; ITF=invasive tumour front.

Figure 2

Figure 2

Disease-specific survival calculated by the Kaplan—Meier method in patients who underwent gastrectomy for resectable gastric cancer (GC). (A) disease-specific survival in patients with or without CD44s expression at the invasive tumour front (ITF); (B) disease-specific survival in patients with or without CD44v6 expression at the ITF; (C) disease-specific survival in patients with or without CD44v9 expression at the ITF; (D) disease-specific survival in patients with the expression of more than one CD44 isoforms at the ITF; all-negative: patients who stained negative for all the CD44 isoforms at the ITF; single-positive: patients showing positive staining for one CD44 isoform at the ITF; double-positive: patients showing positive staining for two CD44 isoforms at the ITF; all-positive: patients showing positive staining for all the CD44 isoforms at the ITF.

References

    1. Al-Hajj M, Wicha MS, Benito-Hernandez A, Morrison SJ, Clarke MF (2003) Prospective identification of tumorigenic breast cancer cells. Proc Natl Acad Sci USA 100(7): 3983–3988. - PMC - PubMed
    1. Bankfalvi A, Piffko J (2000) Prognostic and predictive factors in oral cancer: the role of the invasive tumour front. J Oral Pathol Med 29(7): 291–298. - PubMed
    1. Brown RL, Reinke LM, Damerow MS, Perez D, Chodosh LA, Yang J, Cheng C (2011) CD44 splice isoform switching in human and mouse epithelium is essential for epithelial-mesenchymal transition and breast cancer progression. J Clin Invest 121(3): 1064–1074. - PMC - PubMed
    1. Cao X, Cao D, Jin M, Jia Z, Kong F, Ma H, Wang Y, Jiang J (2014) CD44 but not CD24 expression is related to poor prognosis in non-cardia adenocarcinoma of the stomach. BMC Gastroenterol 14: 157. - PMC - PubMed
    1. Collins AT, Berry PA, Hyde C, Stower MJ, Maitland NJ (2005) Prospective identification of tumorigenic prostate cancer stem cells. Cancer Res 65(23): 10946–10951. - PubMed

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