The study focuses on the improvement of morphological diagnosis and prognostical criteria of gastrointestinal stromal tumors (GISTs), that based on analysis their clinical, morphological and immunohistochemical features. A number of clinicomorphological, histological and imunohistochemical features of primary and recurrent gastrointestinal stromal tumors are described in chapters of this dissertation.
The material was composed of 100 primary GISTs and 30 recurrent GISTs, from patients who had primary resection of tumor and the following treatment with imatinib. The material with primary GISTs was divided into subgroups with different characteristics: based on the site tumors divided into stomach (34 cases) and non-stomach (66 cases), based on histology – spindle cell tumors (91 cases), epithelioid (6 tumors) and mixed (3 tumors), based on the presence or absence of recurrence within 1-3 years after surgical resection – GISTs with replace (37 cases) and without it (63 tumors). The research had two main phases. The first stage was devoted to study of clinical and morphological features of 100 primary and 30 recurrent GISTs. The aim of the second phase was the deep investigation of biological features of GISTs with using of the broad panel of immunohistochemical markers. We selected 36 cases out 100 primary GISTs, those were analyzed in the first phase, among these tumors 12 tumors had relapse within 3 years after surgery and 24 were tumors without relapses in the same period of time. 10 recurrent GISTs were selected out 30 cases those we had in the first stage. The criteria of inclusion were the sufficient amount of material in formalin fixed paraffin embedded blocks and the good quality of this material. The immunohistochemical study was performed with the following primary antibodies: CD117, CD34 and DOG-1 were used to phenotyping of GISTs, to differential diagnosis with leiomyomas and leiomyosarcomas was used smooth muscle actin (SMA), to the study of angiogenesis in tumors – CD31, marker of cellular adhesion – CD44 and marker of neoangiogenesis – vascular endothelial growth factor (VEGF), to the investigation of invasion – matrix metalloproteinase-9 (MMP-9), to analysis of proliferative activity – Ki-67, to analysis of tumor progression properties – p16ink4A; to study the immune profile of GISTs we used antibodies against CD3, CD8 (cytotoxic lymphocytes), CD4 (T-helpers), CD56 (NK-cells), CD45 (leucocyte common antigen), CD68 (macrophages).
Clinical and morphological features of GISTs. According to our study, GISTs were more common among women than among men (65% and 35% respectively). Most GISTs localized in small intestine (38%), the stomach took the second place (34%). Obtained data were similar to data given by WHO. GISTs of jejunum and ileum were the largest by size and had asymptomatic course in 54,5% and anemia in 30,3% of cases. These tumors more often were found in the stage of metastases in other organs. The rarest location were esophagus (only 1 tumor) and duodenum (5 tumors – 5 %). Before histological examination duodenal GISTs were described as carcinomas of the head of pancreas. In our study colorectal GISTs were found more often than it’s described in WHO data (27% cases in our study and 5% according to WHO data). These tumors had usually asymptomatic course and were 5 cm or less in size. Colorectal GISTs in many cases were just incidental findings, among these group of tumors we detected oftener, than among GISTs with other location, synchronous or metachronous malignancies (33,3% of colorectal GISTs). 50% of tumors were found in stage T4, 33% in stage T3, only 17% in stage T2, but affection of regional lymph nodes were described only in 5% of our cases, and metastases in other organs were found in 13% of cases. Liver metastases were found in all cases of primary GISTs with metastases and in 3% of cases were described also metastases in peritoneum and omentum. Among primary GISTs with metastases, 69% had location in small intestine (9 from 13 cases). 37% (37 cases) of primary GISTs in our study gave metastases in period from 1 till 3 years. In general, stomach GISTs regardless of their mitotic activity relapsed rarer than non-stomach GISTs (19% and 25% with mitotic rate ≤5 /5mm2, 30,8% and 54,8% with mitotic rate > 5/5mm2 respectively). This difference had clinical, but didn’t have statistical significance (X2=0,632, p>0,05 and X2=0,131, p>0,05 for groups with low and high mitotic rate respectively).
