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Int J Clin Exp Pathol 2011;4(8):733-741

Original Article
Clinicopathologic significance of putative stem cell markers, CD44 and nestin, in gastric

Sadhna Dhingra, Wei Feng, Robert E Brown, Zhongren Zhou, Thaer Khoury, Rongzhen Zhang, Dongfeng Tan

Pathology, University of Texas MD Anderson Cancer Center, Houston, TX, United States; Pathology and Laboratory Medicine, University of
Texas Health Science Center, Houston, TX United States; Department of Pathology, North Cypress Medical Center, Cypress TX, United States;
Pathology, University of Rochester, Rochester, United States; Pathology, Roswell Park Cancer Institute, Buffalo, United States

Received October 10, 2011; accepted October 27, 2011; Epub October 30, 2011; Published November 30, 2011

Abstract: Cancer stem cells (CSC) are unique subpopulations that have the capacity to drive malignant progression and mediate
radio/chemoresistance. The role of nestin as a CSC marker in gastric adenocarcinoma is largely unknown. Our objective was to evaluate
immunoexpression of CSC markers CD44 and nestin in gastric adenocarcinoma versus non-neoplastic gastric mucosae (NNGM) and
correlate it with various clinicopathologic factors. Tissue microarray blocks from 174 cases of gastric adenocarcinoma and 41 samples of
adjacent NNGM were assembled. Clinical data including patient’s age and sex, tumor histologic subtype and grade, and disease stage were
obtained. Expression of CD44 and nestin was assessed by immunohistochemistry. Expression of membranous CD44 (51%, 78/152) and
cytoplasmic nestin (25%, 43/174) was significantly greater in gastric adenocarcinoma than in NNGM (P<0.001). A subset of cases (n=15) that
co-expressed membranous CD44 and cytoplasmic nestin were significantly more frequent in Lauren intestinal histologic subtype than in
diffuse subtype (P<0.05). Foci of intestinal metaplasia (n=6) showed either CD44 (3/6) or nestin (2/6) expression. This is the first study to report
the clinicopathologic significance of nestin expression in gastric cancers, and to correlate the nestin expression with CD44, another stem cell
marker. The study shows that nestin and CD44, are significantly expressed in a subset of gastric adenocarcinoma, particularly co-expression
of nestin and CD44 is significantly revealed in Lauren intestinal histologic subtype. Their expression is also increased in intestinal metaplasia,
a premalignant lesion. These findings suggest that CSCs may have a pathogenetic role in the pathway of intestinal metaplasia-intestinal type
gastric adenocarcinoma.

Keywords: Stem cell markers, CD44, Nestin, gastric adenocarcinoma

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Address all correspondence to:
Dr. Dongfeng Tan
Department of Pathology
University of Texas MD Anderson Cancer Center
Houston, TX, USA.