The Study On Molecular And Clinical Characteristics Of Esophageal Gastrointestinal Stromal Tumors And Its Surgical Treatment

Objective:Esophageal gastrointestinal stromal tumors (GISTs) are clinically less happened mesenchymal esophageal tumors, but due to the success of the treatment to GISTs by drug target technique, it becomes an elegant example of "bench to bedside" medicine in deal with solid tumors, which promotes scientists to pay more attention to esophageal GISTs. In recent years, there are some reports about it both nationally and internationally, but most of them are case reports except few papers with relatively large sets of cases which focused on pathology. In general, up to date there is little systemic research about esophageal GISTs with large sets of cases. In order to recognize the disease deeply so that we could definitely diagnose and effectively treat the disease, improve the chances for surgical removal, prolong the survival rate and decrease the mortality, we carried out a preliminary study on the clinical, pathological, and genetic characteristics as well as biological behavior of esophageal GISTs using relatively large sets of cases both histologically and genetically.Materials and methods:1) we collected 63 samples surgically completely removed from patients diagnosed as esophageal mesenchymal tumors from the year 1978 to 2008 in the First and the Second Hospital of Lanzhou University by retrieving case archives, eight of them were diagnosed as esophageal GISTs by hematoxylin and eosin staining and immunohistochemistry, all of the eight patients were followed up respectively, and corresponding clinical and follow-up data were analyzed.2) we collected the above diagnosed paraffin-embedded samples, and genomic DNA were extracted from the tissues, then exons 9,11,13 and 17 of c-kit gene as well as the exons 12 and 18 of PDGFRA gene were detected for mutations, and analyzed combined with clinical data.Results:Eight of the 63 patients with esophageal mesenchymal tumors were diagnosed as esophageal GISTs (which was about 12.7% of those esophageal mesenchymal tumors), among which the rate of male to female was 5:3, median age was 57 years old, dysphagia was the most common symptom. The tumors located at the lower third of esophagus, five of them occurred in the distal esophagus and the gastro-esophageal junction. All the eight patients were surgically treated either by elucleation or by esophagectomy plus esophagogastrostomy. The pathological examination after surgical operation was done and no lymph node metastasis was found, the patients were not diagnosed as esophageal GISTs both pre-and post-operation. No radiation, chemical treatment and neoadjuvant imatinib therapy were used to the patients pre-or post-operation too. The median follow-up was 59 months, four of the eight patients had distal metastasis and local recurrences, and died of it, among which two patients had the liver metastasis. Sequencing was used to detect the gene mutation, exon 11 of c-kit gene was mutated in two patients, but the mutation in exons 9,13,17 of c-kit gene and exons 12,18 of PDGFRA gene were not found. Among the two patients with c-kit gene mutation, one was deletion (codons AAG, GTT, GTT at the sites 558-560 were deleted), another was point mutation (the codon GTT at the site 559 mutated to GAT). Conclusions:1) Esophageal GISTs is a less occurred tumor derived from esophageal mesenchyme with high mortality and recurrent rate, especially those with relatively larger tumor sizes (>9 centimeters). It is usually difficult to be diagnosed before surgical operation.2) It is a prerequisite for the diagnosis and differential diagnosis of esophageal GISTs to examine the samples immunohistochemically post operation. Frequently used biomarkers are CD117, CD34, SMA, S-100 and so on.3) Surgical operation is still the principal and preferred method to deal with esophageal GISTs. The criteria to a successful operation of esophageal GISTs is to completely remove the tumor with its pseudo-capsule as well as the surrounding tissues attached with it as possible as we can, i.e., R0 resection. Esophageal gastrointestinal stromal tumors principle of operation is:RO resection of the tumor under the premise of taking as much as possible to reduce functional damage of surgery.4) Mitotic index, Ki-67 labeling index, tumor size, complete extent of surgical operation and the original site of the tumor are the important factors to the prognosis of esophageal GISTs.5) Genetically esophageal GISTs can be divided into three types:c-kit mutated, PDGFRA mutated and wild type, among which mutation of c-kit gene is mostly occurred, functional mutation of c-kit gene is the most important molecular event to the occurrence of esophageal GISTs.6) The mutation in exon 11 of c-kit gene probably indicates the ominous biological behavior and prognosis of esophageal GISTs.