الفهرس 
Aim of the workOnly 14 pages are availabe for public view
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Abstract
Gastrointestinal stromal tumours (GIST) are the most common mesenchymal tumours of the digestive tract, account for 0.1–3% of all gastrointestinal cancers. Although rare, GIST are of clinical relevance because 10–30% of cases are malignant.
Most tumors occur in stomach (60%), small intestine (30%), duodenum (4-5%), followed by colon (4%) esophagus (1-2%) and rectum (1-2%). GISTs have also been rarely reported in the appendix and gallbladder. GIST may rarely appear at extravisceral locations, such as the mesentery, pelvis, omentum, and retroperitoneum. Tumors appearing in the previous locations are named “extra gastrointestinal GIST” (E-GIST).
The biological behaviour of GIST, and its potential malignancy are difficult to be expected. Therefore, it was a point of scientific research attraction during the past decade.
ROR2 is a signaling receptor for Wnt ligands. ROR2 is a member of the receptor tyrosine kinase orphan receptor (ROR) family, which belongs to the receptor tyrosine kinase (RTK) superfamily. ROR2 has a dual role in tumor development, being able to act either promoting or inhibiting cancer progression in different tumors, a feature also described for other developmental pathways, such as Notch.
The aim of the present work was to investigate the prognostic role of ROR2 expression in GIST. This is a retrospective study that included 56 cases of GIST.
Formalin fixed, paraffin embedded (FFPE) tissue blocks were retrieved from the archival material of National Cancer Institute, Cairo University during the period between “2010 – 2013”. The diagnosis of GIST was confirmed by positive expression of c-KIT immunostaining in all cases except 5 negative cases that were positive for PDGFRA immunostaining. We studied the ROR2 and Ki 67 expression in GIST cases and their correlation with different clinicopathological parameters.
ROR2 cytoplasmic expression was positive in 40 cases (71.4%). Strong ROR2 staining was seen in 28 cases (50%), moderate staining in 9 cases (16 %), and mild in 3 cases (5.4%). The current study revealed that ROR2 strong immunostaining was significantly correlated to prolonged overall survival of GIST patients. In addition, ROR2 positivity and percentage of immunostaining were inversely related to tumor progression. The present results showed no significant association between ROR2 expression and different clinicopathological parameters including age, gender, site, size, LN, patient status, distant metastasis, morphology, mitosis, INH risk category as well as 2006 risk category.
Ki 67 is a nuclear antigen that is closely related to cell mitosis and serves as an indicator of cell division and proliferation; thus Ki 67 exists in actively proliferating cells. It is expressed in all phases of the cell cycle in stages G1, S, and G2. Ki 67 can recognize most of the proliferating cells except for G0, whereas, the mitotic index reflects the M stage of mitosis only.
The cut-off point of Ki 67 in the present study was 3% which represents the median. The present results demonstrated a significant association between Ki 67 proliferative index and GIST risk category (2006 risk category) and between Ki 67 proliferative index and mitotic rate. However, no significant association between Ki67 and other parameters including overall survival was found.
C-KIT cytoplasmic expression was positive in 51 cases (91.07%) while 5 cases (8.93%) were negative. The current study revealed that c-KIT expression has no significant statistical correlation with clinicopathological data, ROR2 expression, Ki 67 expression or with overall survival of studied cases.