World Congress of Gastroenterology

WCOG 2019


 
ASSOCIATION OF NOTCH SIGNAL PATHWAYS AND TARGET PROTEINS, AND MATRIX METALLOPROTEINASES WITH PROGRESSION, INVASION AND METASTASIS OF GASTRIC ADENOCARCINOMA TUMORS
ADEM AKCAKAYA 1 ELİF YAPRAK SARAÇ 2 MUSTAFA HASBAHÇECİ 1 FATMA BETÜL AKÇAKAYA 3 NURCAN ÜNVER 4 GANİME ÇOBAN 5 BURCU GÜL 5 TUĞBA KOTİL 2 İLKAY ÖZDEMİR 2 SEYHUN SOLAKOĞLU 2

1- DEPARTMENT OF GENERAL SURGERY, FACULTY OF MEDICINE, BEZMIALEM VAKIF UNIVERSITY
2- DEPARTMENT OF HISTOLOGY AND EMBRYOLOGY, ISTANBUL FACULTY OF MEDICINE
3- FACULTY OF MEDICINE, BEZMIALEM VAKIF UNIVERSITY
4- DEPARTMENT OF PATHOLOGY, YEDIKULE CHEST DISEASES AND THORACIC SURGERY TRAINING AND RESEARCH HOSPITAL
5- DEPARTMENT OF PATHOLOGY, FACULTY OF MEDICINE, BEZMIALEM VAKIF UNIVERSITY
 
Background/Aims:

Most components of Notch signaling are strongly expressed at different levels in gastric carcinoma tissue samples and are associated with a considerable number of clinical parameters. This study was to investigate the role of Notch signaling with its receptors and the expression of matrix metalloproteinases (MMP2 and MMP9) in the metastasis and invasion of GAC.

Materials and Methods:

A total number of 77 patients undergoing total / subtotal gastrectomy for GAC were included in the study, and followed up postoperatively for five years. Their postoperative histopathological findings, clinical course, metastatic status, and mortality rates were recorded. The expressions of four Notch receptors (Notch1, Notch2, Notch3, Notch4), two Delta/Serrate Ligand domain (DSL) ligands DLL1 and DLL3, and potent downstream targets MMP2 and MMP9 were evaluated by immunohistochemistry (IHC) and correlated with clinical and pathological findings.

Results:

Seventy-three out of 77 patients completed the follow-ups. Most of patients had a tumor located in gastric antrum with a mean size of 6.15 ± 3.47 cm. 54.8% of them had a metastasis, 57.5% had a morbidity, 47.9% was re-hospitalized frequently due to a post-operative complication, and two of the patients died in the first post-operative year.

The immunoreactivities of Notch1, Notch2, Notch3, Notch4 elevated with increasing depth of invasion and lymph node metastasis, especially in T4 stage (P<0.0001), while DLL1 and DLL3 decreased in T4 stage (P<0.0001). Only Notch4 increased significantly in the tumors with known distant metastasis while only DLL1 decreased in those tumors (P<0.05). MMP2 and MMP9 reactivities were highest in stroma of tumors in T4 (P<0.0001) and N3 stage with a distant metastasis (P<0.05).

Conclusion:

This is the first follow-up study on Notch signaling with their receptors DLL1 and DLL3, and MMP2 and MMP9 immunoreactivities in human GAC. Our preliminary findings suggest increased expression of Notch pathway and MMPs might be involved in the progression, migration and invasion to the submucosa of gastric wall, to the lymph nodes and even in the distant metastasis of the tumoral cells. 

Keywords:

Gastrectomy, gastric adenocarcinoma, Notch, MMP, DLL