Abeer A Bahnassy1, Thanaa El-A Helal2, Ibrahim Mh El-Ghazawy3, Gamal F Samaan4, Moataz M Galal El-Din5, Mona S Abdellateif6, Eman Desouky7, Abdel-Rahman N Zekri8. 1. Tissue Culture and Cytogenetics Unit, Pathology Department, NCI, Cairo University, Egypt. Electronic address: chaya2000@hotmail.com. 2. Pathology Department, Faculty of Medicine, Ain Shams University, Egypt. 3. Surgery Department, Faculty of Medicine, Ain Shams University, Egypt. 4. Clinical Pathology Department, Mataryia Teaching Hospital, Cairo, Egypt. 5. Surgery Department, Mataryia Teaching Hospital, Egypt. 6. Molecular Virology and Immunology Unit, Cancer Biology Department, NCI, Cairo University, Egypt. Electronic address: mona.sayed@nci.cu.edu.eg. 7. Epidemiology and Biostatistics Department, NCI, Cairo University, Egypt. 8. Molecular Virology and Immunology Unit, Cancer Biology Department, National Cancer Institute, Cairo University, Cairo, Egypt.
Abstract
BACKGROUND: We assessed the role of E-cadherin (CDH1), runt-related transcription factor 3, p21waf and p27 promoter methylation (PM) and protein expression in Helicobacter pylori (HP)-associated gastric carcinomas (GCs) and adjacent non-neoplastic tissues (ANNTs). PATIENTS AND METHODS: 192 cases were assessed for PM and protein expression of CDH1, RUNX3, p21waf and p27 by methylation-specific PCR (MSP) and immunohistochemistry. The CagA gene was also assessed. RESULTS: In GCs, 66 (34.4%) and 84 (43.8%) cases showed CDH1-PM and reduced expression. It is significantly affected in GCs rather than in non-neoplastic groups (p < 0.001). In ANNTs, 108 (56.3%) cases showed CDH1-PM and all cases revealed preserved protein expression. RUNX3-PM was detected in 78 GCs (40.6%) and 69 ANNTs (35.9%), whereas reduced protein expression was detected in 99 (51.65%) GC compared to ANNTs 90 (46.9%). p21WAF and p27 showed PM in (48.4% and 45.3%) GCs and ANNTs; respectively. p21waf protein was reduced in 90 (46.9%) cases and 91 ANNTs (47.4%). p27 was reduced in 86 (44.8%) cases and 87 ANNTs (45.3%). CDH1 aberrations correlated with HP in tumors and ANNTs and with diffuse/intestinal tumors (p = 0.014, p = 0.014 and p = 0.02). RUNX3 aberrations associated with HP (p = 0.04), high grade (p = 0.04), and advanced stage (p = 032). Tumor grade associated with RUNX3-PM, CDH, p21 and p27 protein (p < 0.05 for all). Tumor stage associated significantly with PM and reduced protein expression of all markers. Positive lymph nodes associated significantly with p27PM (p < 0.001). CONCLUSIONS: HP plays an important role in the development and progression of GC through silencing of CDH1, RUNX3, p21WAF and p27 expression.
BACKGROUND: We assessed the role of E-cadherin (CDH1), runt-related transcription factor 3, p21waf and p27 promoter methylation (PM) and protein expression in Helicobacter pylori (HP)-associated gastric carcinomas (GCs) and adjacent non-neoplastic tissues (ANNTs). PATIENTS AND METHODS: 192 cases were assessed for PM and protein expression of CDH1, RUNX3, p21waf and p27 by methylation-specific PCR (MSP) and immunohistochemistry. The CagA gene was also assessed. RESULTS: In GCs, 66 (34.4%) and 84 (43.8%) cases showed CDH1-PM and reduced expression. It is significantly affected in GCs rather than in non-neoplastic groups (p < 0.001). In ANNTs, 108 (56.3%) cases showed CDH1-PM and all cases revealed preserved protein expression. RUNX3-PM was detected in 78 GCs (40.6%) and 69 ANNTs (35.9%), whereas reduced protein expression was detected in 99 (51.65%) GC compared to ANNTs 90 (46.9%). p21WAF and p27 showed PM in (48.4% and 45.3%) GCs and ANNTs; respectively. p21waf protein was reduced in 90 (46.9%) cases and 91 ANNTs (47.4%). p27 was reduced in 86 (44.8%) cases and 87 ANNTs (45.3%). CDH1 aberrations correlated with HP in tumors and ANNTs and with diffuse/intestinal tumors (p = 0.014, p = 0.014 and p = 0.02). RUNX3 aberrations associated with HP (p = 0.04), high grade (p = 0.04), and advanced stage (p = 032). Tumor grade associated with RUNX3-PM, CDH, p21 and p27 protein (p < 0.05 for all). Tumor stage associated significantly with PM and reduced protein expression of all markers. Positive lymph nodes associated significantly with p27PM (p < 0.001). CONCLUSIONS:HP plays an important role in the development and progression of GC through silencing of CDH1, RUNX3, p21WAF and p27 expression.
Authors: Tim Marwitz; Robert Hüneburg; Isabel Spier; Jan-Frederic Lau; Glen Kristiansen; Philipp Lingohr; Jörg C Kalff; Stefan Aretz; Jacob Nattermann; Christian P Strassburg Journal: Cancers (Basel) Date: 2020-12-11 Impact factor: 6.639