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. 2011 Aug 23;105(5):658-65.
doi: 10.1038/bjc.2011.287. Epub 2011 Aug 9.

Sequential expression of putative stem cell markers in gastric carcinogenesis

T Wang  1 , C W Ong, J Shi, S Srivastava, B Yan, C L Cheng, W P Yong, S L Chan, K G Yeoh, B Iacopetta, M Salto-Tellez
Affiliations

Sequential expression of putative stem cell markers in gastric carcinogenesis

T Wang et al. Br J Cancer. .

Abstract

Background: Gastric carcinogenesis has been well documented in the step-wise histopathological model, known as Correa pathway. Several biomarkers including CD44, Musashi-1 and CD133 have been reported as putative stem cell (PSC) markers.

Methods: We investigated expression of PSC markers CD44, Musashi-1 and CD133 in relation to gastric carcinogenesis and prognosis and chemoresponse. Immunohistochemistry staining was performed in gastric cancer (GC) clinical specimens representing different steps of the Correa pathway. Gastric cancer samples taken before and after neoadjuvant chemotherapy with docetaxel, cisplatin and capecitabine (DCX) were also evaluated for PSC marker expression.

Results: We showed that the expression of three PSC markers was significantly elevated in GC relative to normal gastric mucosa (P<0.001 for each marker). Precancerous lesions, including intestinal metaplasia and dysplasia, demonstrated increased expression of CD44 and Musashi-1. CD133 was predominantly expressed along the border between intramucosal carcinoma and connective tissue at later stages. High CD44 and CD133 expression showed prognostic value for worse patient survival (P=0.014 and P=0.019, respectively). A small number of tumours with high expression of CD44 and CD133 showed pathological response to DCX-based neoadjuvant chemotherapy.

Conclusion: CD44 and Musashi-1 are frequently expressed in both premalignant gastric lesions and invasive GC, whereas CD133 expression is restricted mainly to neoplastic tissues.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Putative stem cell marker expression during the Correa pathway of gastric carcinogenesis. Representative images of normal, gastritis, intestinal metaplasia (IM) and malignant (GC) epithelial tissues from gastric specimens are shown following immunohistochemical staining for CD44 (E–H), Musashi-1 (I–L) and CD133 (M–P). Representative haematoxylin and eosin (H&E) stains (A–D) and immunohistochemical staining for Ki67 (Q–T) are also shown.
Figure 2
Figure 2
Frequency of positive expression for PSC markers along the Correa pathway. Values were determined following immunohistochemical staining and scoring as described in the Materials and Methods section.
Figure 3
Figure 3
Expression of PSC markers as revealed by immunohistochemical staining on full-face sections of intestinal type GC. Representative images of CD44 and Musashi-1 expression in low grade dysplasia (A and D (arrows)), high grade dysplasia (B and E (stars)) and invasive cancer (C and F), as well as CD133 in intramucosal carcinoma (G) and invasive cancer (H).
Figure 4
Figure 4
Kaplan–Meier survival analysis of GC patients according to expression levels for the PSC markers CD44 and CD133.
Figure 5
Figure 5
Expression of PSC markers in pretreatment biopsies of GC. Four tumours showed pathological response to treatment (R) and four tumours did not (NR). A significant difference between R and NR tumours was observed for the average expression level of CD44 and CD133 (P<0.05 for each).
Figure 6
Figure 6
Changes in the expression of PSC markers following neoadjuvant chemotherapy of GC. Tumours showing pathological response are shown separately to those in which no response was observed.
Figure 7
Figure 7
Schematic representation of PSC marker expression along the Correa pathway. The expression of CD44 and Musashi-1 is frequently observed in IM, dysplasia and invasive cancer stages, whereas CD133 expression is observed at the intramucosal carcinoma and invasive cancer stages.
See this image and copyright information in PMC

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