World Congress of Gastroenterology

WCOG 2019


 
CORRELATION OF NOTCH SIGNAL PATHWAYS AND TARGET PROTEINS, AND MATRIX METALLOPROTEINASES WITH TYPE OF GASTRIC ADENOCARCINOMA TUMORS
ELİF YAPRAK SARAÇ 1 ADEM AKCAKAYA 2

1- DEPARTMENT OF HISTOLOGY AND EMBRYOLOGY, ISTANBUL FACULTY OF MEDICINE, ISTANBUL UNIVERSITY, ISTANBUL, TURKEY
2- DEPARTMENT OF GENERAL SURGERY, FACULTY OF MEDICINE, BEZMIALEM VAKIF UNIVERSITY, ISTANBUL, TURKEY
 
Background/Aims:

Most memberMost member of Notch pathways are known to be strongly expressed in gastric carcinomas, resulted in an increase of cancer cell proliferation and prevention of apoptosis. There is still a lack of understanding of the molecular mechanisms of Notch signaling in gastric carcinoma, hence, we aimed to investigate the association between Notch signaling with its receptors and the expression of matrix metalloproteinases (MMP2 and MMP9), and the gastric adenocarcinoma pattern.

Materials and Methods:

A total number of 73 patients (54 male, 19 female) undergoing total / subtotal gastrectomy for gastric adenocarcinoma were included in the study. The mean of age was 61.37 ± 10.49. 29 (39.7%) patients undergone a subtotal gastrectomy while 44 (60.3%) undergone a total operation. The mean duration of hospitalization was 7.42 ± 2.16 and 66 (90.4%) of patient had comorbidities. Their postoperative histopathological findings and clinical course were recorded. The expressions of four Notch receptors (Notch1, Notch2, Notch3, Notch4), two ligands DLL1 and DLL3, and potent downstream targets MMP2 and MMP9 were evaluated by immunohistochemistry (IHC) and correlated with clinical and pathological findings.

Results:

Pathological analysis of the tumors showed that 32 (43.8%) of the patients had an intestinal type of adenocarcinoma, while 39 (53.4%) had diffuse type. Most of the patients (63%) had low-differentiated tumor (G3). Diffuse adenocarcinomas showed a higher positivity for Notch 1, Notch 2, Notch 3 and Notch 4 (P<0.05 for all), a lower positivity for DLL1 (P<0.05) but not DLL3, and a higher positivity for MMP2 and MMP9 in the tumoral stroma (P<0.05 for both), compared with the intestinal type.

Conclusion:

This is the first study on Notch signaling with their receptors DLL1 and DLL3, and MMP2 and MMP9 immunoreactivities in human GAC, reporting the correlation between the Lauren type of tumor and aforesaid proteins. 

Keywords:

 Gastric adenocarcinoma, Notch, MMP, DLL