Characterization of an Lgr5-Positive Stem Cell Population in Gastric Cancer Tissues and Background Gastric Mucosa.
Deqin Ma, Yuan Yao, Amy Ziober, Antonia R Selpulveda. U of Pennsylvania, Philadelphia
Background: Lgr5 (Gpr49), is an orphan G protein-coupled receptor that is expressed in epithelial stem cells in intestine and stomach, and in cancer tissues, marking cancer stem cells. The role of gastric stem cells in H. pylori (HP)- associated gastric cancer is not well understood. In this study, we examined the expression of Lgr5 in gastric mucosa and gastric cancer tissues to determine whether the Lgr5-positive stem cell population is related to the type of mucosa (antral vs. oxyntic), H. pylori infection status, and gastric cancer subtypes.
Design: Twenty non-neoplastic and 17 tumor tissue blocks from the same patients were selected from a retrospective cohort of gastrectomy specimens. The specimens were grouped based on the presence or absence of gastric adenocarcinoma (GC) and H. pylori status: HP negative patients without GC (HP-/GC-), HP negative patients with GC (HP-/GC+), and HP positive patients with GC (HP+/GC+). The latter two were subdivided into mucosa with no tumor in the block or with tumor. H. pylori status and Lgr5 expression were determined by immunohistochemical staining with specific rabbit polyclonal antibodies. The intensity of Lgr5 stain was graded as: 0, no stain; 1, intermediate stain; and 2, strong stain. The overall percentage of positivity (stain grades 1 or 2) was scored. The neck and deep glandular components were graded separately. P values<.05 were considered significant.
Results: Lgr5 was significantly more expressed in the antrum than in oxyntic mucosa, with focal expression scores up to 14.0 ±1.8 and 2.0 ±2.2, respectively (p=.005). Significantly higher Lgr5 expression was seen in HP+/GC+ mucosa (n=8) compared with the HP-/GC+ group (n=12) (13.8 ±3.0 and 6.5 ±1.5, respectively, p=.031), with a 4-fold increase in the neck region (p=.02). Lgr5 expression was present in 70.6% (12 of 17) carcinomas. Expression of Lgr5 was rare in moderately differentiated adenocarcinoma areas as compared to poorly differentiated areas (1 of 6 vs. 12 of 15, p=.007). Lgr5 expression was higher in tumors from the HP-/GC+ group vs. the HP+/GC+ group (median: 5.0 and 0.0, respectively, p=.03).
Conclusions: The Lgr5-positive epithelial stem cell pool is expanded during H. pylori gastritis. The population of Lgr5-positive gastric stem cells appears to be associated with poorly differentiated adenocarcinomas, both in HP-positive and HP-negative stomachs. These data support the notion that Lgr5-positive cells represent a population of gastric cancer stem cells and may be important targets of H. pylori-associated gastric carcinogenesis.
Wednesday, March 2, 2011 1:00 PM
Poster Session VI # 236, Wednesday Afternoon