Stem Cell Markers CD44 and Nestin in Human Esophageal Adenocarcinoma and Its Precursor Lesions
W Feng, Z Zhou, D Tan. The University of Texas Medical School at Houston, Houston; University of Rochester Medical Center, Rochester; The University of Texas M.D. Anderson Cancer Center, Houston
Background: Recently, there has been mounting evidence for the existence of cancer stem cells within solid tumors of the colon, pancreas, breast, and prostate. CD44 and nestin are two stem cell markers that are known to be present in colorectal carcinoma and gastrointestinal stromal tumors, respectively. The expression of these two stem cell markers in esophageal adenocarcinoma (EAC) and its precursor lesions, including distinctive-type Barrett mucosa (BM) (intestinal metaplasia) and esophageal columnar dysplasia (ECD), is largely unknown. In this study, we evaluated the expression of CD44 and nestin in EAC and its precursor lesions.
Design: We evaluated samples from 135 cases of EAC, 40 ECD (15 high grade and 25 low grade), 37 BM without ECD, and 164 non-neoplastic esophageal mucosa (NNEM), without ECD or BM, in formalin-fixed, paraffin-embedded tissue microarray blocks. Tissues were stained with antibodies against CD44 and nestin. The intensity (1-3+) and percentage of positive nuclear-staining cells were determined. The significance of difference in means was determined by student's t-test.
Results: Most EAC cases showed 1-3+ membranous staining for CD44 (91 of 135 [67%]), and a subset of CD44-positive cases showed 1-3+ cytoplasmic staining for nestin (40 of 135 [30%]). Overall, EAC showed higher nestin expression compared to NNEM (p<0.005). Poorly differentiated EAC had statistically significant higher expression of both CD44 and nestin than did moderately and well differentiated EAC (p < 0.05). Most ECD cases (35 of 40 [87%], 22 low grade and 13 high grade) showed 1-2+ membranous staining for CD44. A subset of ECD cases (13 of 40 [33%], 9 low grade and 4 high grade) showed 1+ cytoplasmic staining for nestin. Most NNEM tissues showed 1-3+ membranous staining for CD44 (128 of 164 [78%]) and a few showed 1-3+ cytoplasmic staining for nestin (8 of 164 [5%]) predominantly in basal/parabasal squamous epithelial cells. Most BM showed 1-2+ membranous staining for CD44 (32 of 37 [86%]), and a subset showed 1-2+ cytoplasmic staining for nestin (7 of 37 [19%]).
Conclusions: In this study, we identified stem cell markers in EAC and its precursor lesions. These markers may serve as therapeutic targets for EAC. Further study is needed to elucidate the prognostic implications of stem cells in EAC.
Wednesday, March 24, 2010 9:30 AM
Poster Session V # 76, Wednesday Morning