Expression of Stem Cell Markers in Human Gastric Adenocarcinoma and Non-Neoplastic Gastric Mucosa, a Study of 209 Cases
S Dhingra, W Feng, D Zhou, T Khoury, RE Brown, D Tan. MD Anderson Cancer Center, Houston; UT Health Science Center, Houston; University of Rochester, Rochester; Roswell Park Cancer Institute, Buffalo
Background: Cancer stem cells (CSCs) are a unique subpopulation that possesses the capacity to repopulate tumors, drive malignant progression and mediate radio/chemoresistance. Stem cell markers, CD44 and nestin, are known to play a role in disease progression in colorectal carcinoma. Recent studies suggest that CD44 expressing gastric cancer cells show increased resistance for chemotherapy or radiation-induced cell death. Role of nestin as a CSC in gastric adenocarcinoma (GAC) is largely unknown. In this study we evaluated the expression of CD44 and nestin in GAC.
Design: Tissue microarray blocks from 168 cases of GAC and 41 adjacent non-neoplastic gastric mucosa (NNGM) were assembled. Immunohistochemical stains were performed using antibody against CD44 and nestin. The intensity (1-3+) and percentage of chromogenic signal was determined, and a composite score (CS), the product of the intensity and percentage was calculated. The significance of difference in means was determined by paired student's t-test.
Results: Membranous CD44 was positive in 52% (79/151) cases of GAC. Majority of CD44 positive cases (60/79 [75%])} showed strong (2-3+) signal intensity with 49% (39/79) displaying CS > 100 (range 5-270). In contrast, adjacent NNGM showed expression of CD44 in 24 % (10/41) cases. Nestin was localized in the cytoplasm and 23% (38/168) cases of GAC were positive. Strong (2-3+) intensity of staining was seen in 92% (35/38) cases and 57% (22/38) showed CS>100 (range 5-240). A subset of nestin positive cases (16/38 [42%]) showed (1-3+) membranous staining of CD44. Some cases with intestinal metaplasia (IM) showed either CD44 (3/6) or nestin (2/6) expression. Few NNGM (2/41 [5%]) showed nestin positivity. GAC showed statistically higher expression of nestin compared to NNGM (p<0.001).
Conclusions: This study reveals that overexpression of stem cell marker, nestin, in GAC is significantly increased versus NNGM. In addition, IM, a common premalignant lesion, also displays increased expression of stem cell markers. These findings suggest that elevated expression of stem cell markers may be associated with development and progression of GAC. Further studies using animal models and cell culture will elucidate the potential of using specific agents to target stem cells in management of GAC.
Tuesday, March 23, 2010 1:00 PM
Poster Session IV # 65, Tuesday Afternoon