[596] Helicobacter Pylori Infection Is Associated with an Increase in the Stem Cell Population in Gastric Mucosa

Q Ahmed, R Tawil, P Sochacki, N Khoury, J Du, B Patel, AP Majumdar, E Levi. Wayne State University, Detroit, MI; Karmanos Cancer Institute, Detroit, MI; John D. Dingell VAMC, Detroit, MI

Background: Evidence supporting a causal relationship between gastric dysplasia, carcinoma and Helicobacter pylori (HP) infection has been demonstrated previously. Growing evidence firmly supports that Cancer stem cells (CSCs) exist in a wide array of solid tumors. However the presence and origin of these CSCs in gastric cancer remains to be elucidated. We conducted a pilot study at our institution to possibly identify these CSCs by immunohistochemical (IHC) markers, in precursor lesions of gastric cancer, including early events such as HP gastritis.
Design: Gastric biopsies and resection specimens representing normal (n=10), HP without intestinal metaplasia (IM) (n=12), HP with IM (n=10) and gastric adenocarcinoma (n=12) were identified. These cases were evaluated for stem cell markers CD166, ALDH1 and LGR5 by IHC. We defined positivity in normal and HP cases as membranous and cytoplasmic staining in number of cells per gland (CPG). For cancer cases we used percentage of tumor cells to define positivity. Statistical significance was assessed by Chi Square test.
Results: Of the normal cases 8 /10 showed 1-2 CPG positive for ALDH1, 10/10 showed 1-2 CPG positive for LGR5, however CD166 did not stain any glandular cells. 12/12 cases of HP without IM showed 5-6 CPG positive for ALDH1, 4-5 CPG positive for CD166 and 4-5 CPG positive for LGR5. 10/10 cases of HP with IM showed 7-8 CPG positive for ALDH1, 5-6 CPG positive for CD166 and LGR5. Of the 12 cancer cases 85% were positive for ALDH1, 75% were positive for CD166 and 70% were positive for LGR5. The level of positivity ranged from 5 to 40% of the tumor cells. Staining was more prominent in the invasive fronts and lymph node metastases.

nALDH1CD166LGR5
Normal101-201-2
HP without IM125-6*4-5*4-5*
HP with IM107-8*5-6*5-6*
Gastric adenocarcinoma1285%75%70%
*p<0.05 compared to normal


Conclusions: The increased number of ALDH1, CD166 and LGR5 positive cells in HP gastritis indicates that activation of stem cells which presumably constitute the clonogenic cells of future cancers in the field of inflammation is an early event and constitutes an important step in the progression of advanced disease. The next step would be to determine whether the stem cells that are activated carry genetic hits that will progress to full blown cancer.
Category: Gastrointestinal

Monday, March 22, 2010 9:30 AM

Poster Session I Stowell-Orbison/Surgical Pathology/Autopsy Awards Poster Session # 84, Monday Morning

 

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