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

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.