The management of GISTs is generally based on tumor size because biopsy is not recommended and mitotic index cannot be easily and accurately determined . The National Comprehensive Cancer Network recommends surgical resection for tumors greater than 2 cm because of malignant potential, and lesions less than 2 cm can be conservatively followed up . As a result, the malignant potential of small gastric GISTs could not be accurately determined due to the lack of mitotic index based on pathology. However, every GIST is now regarded as potentially malignant, and even GISTs with low mitotic rates were reported to recur locally or to metastasize . The present study sought to identify the clinical and pathological features of small gastric GISTs and to discuss the treatment strategy of small gastric GSITs.
As a specific marker of GISTs, CD117 has good sensitivity and was highly expressed in nearly 85% to 94% of cases . The high sensitivity and specificity of CD117 is a useful marker in differentiating GIST from other mesenchymal tumors of the gastrointestinal tract. DOG1 (Discovered on GIST-1) is a newly identified marker of GISTs, West et al. reported ubiquitous expression of DOG-1 in GISTs and demonstrated the immunoreactivity for DOG-1 in 97.8% of GISTs . Many reports showed that the sensitivity for CD117 and DOG1 are almost the same, and the two factors have consistency. As a hematopoietic progenitor cell antigen, CD34 is commonly present in GISTs but is less specific than CD117 and DOG1. The positive rate of CD34 is approximately 60% to 70% . In our present study, the clinical and pathological characteristics of small gastric GISTs were in agreement with the references reported. These indicate that there is no significant difference in the clinical and pathological features between the small gastric GISTs in our study and the GISTs reported previously.
Tumor size and mitotic index are the best prognostic indicators for determining the malignant potential of GISTs . In our present study, although all the gastric GISTs were less than 2 cm, the mitotic index of 14 small gastric GISTs was greater than 5 per 50 HPF. It was striking to observe that 22.22% of small gastric GISTs showed low risk, which indicated the malignant potential and implied the necessity of surgical resection of small gastric GISTs. Furthermore, we analyzed the relationship between tumor size (≤1 cm versus 1 to 2 cm) and mitotic index. We found that there was no significant difference between the two groups, and the mitotic index of 4 out of 33 gastric GISTs (≤1 cm) was greater than 5 per 50 HPF. In this situation, we think that all GISTs should be resected once diagnosed. Besides tumor size and mitotic index, the location of GIST is also considered as one of the risk factors. It is reported that the location of GISTs in the gastric cardia and gastroesophageal junction is an unfavorable prognostic factor . In our present study, 8 gastric GISTs were located in the gastric cardia, and the mitotic index of 4 cases exceeded 5, demonstrating that GISTs located in the gastric cardia possess more malignant potential than those located in the gastric fundus and gastric body.
The current management policy for gastric GISTs less than 2 cm is usually conservative, unless tumors grow or symptoms occur . In our present study, 46 of 63 cases (73.02%) were presented with symptoms including pain, bleeding and discomfort. The high rate of presenting symptoms resulted from the combination of gastric cancer and gastric GIST of patients in our study. Even in the remaining 17 asymptomatic patients, the mitotic index of 2 cases was more than 5 per 50 HPF, indicating malignant potential. These findings also indicate that gastric GISTs less than 2 cm should be resected once diagnosed because most of the small gastric GISTs presented with symptoms, and some asymptomatic cases possessed malignant potential.
In 1998, Hirota et al. reported their groundbreaking discovery of KIT mutations in GISTs. It is now established that 70% to 80% of GISTs harbor a KIT gene mutation . Most of these are exon 11 mutations, which cause constitutively activated receptors leading to unregulated autophosphorylation of the intracytoplasmic tyrosine kinases . KIT mutations in exons 9, 13 and 17 are less common and have been associated with more aggressive tumor behavior . PDGFRA mutations occur in approximately 20% to 25% of gastric GISTs, and most commonly in exon 18 . KIT and PDGFRA mutations are mutually exclusive . Very rare cases may have mutations in the BRAF kinase . GISTs without a mutation in either KIT or PDGFRA genes account for about 10% to 15% of GISTs and are known as wild type . In our present study, 74.60% of small gastric GISTs harbor a KIT exon 11 mutation, 4 cases (4.76%) harbor a KIT exon 9 mutation, one case (1.59%) harbors a KIT exon 13 mutation and one case (1.59%) harbors a KIT exon 17 mutation. One case (1.59%) harbors a PDGFRA exon 18 mutation, and 10 cases (15.87%) were wild type. These results demonstrate that the gene mutation spectrum of small gastric GISTs in our present study is in agreement with the references reported.
Some authors have proposed the use of Ki-67 as a more objective parameter for risk assessment, because multivariate analyses in several studies do indicate that Ki-67 index could be independently used as an outcome predictor . In our present study, the consistency of the mitotic index and Ki-67 expression was analyzed using McNemar’s test and the Kappa test. The results showed a good consistency between mitotic index and Ki-67 expression. This indicated that Ki-67 expression may also be considered as a prognostic indicator for determining the malignant potential of gastric GISTs.
There are several limitations in the present study. First, no recurrence-free survival rate of patients who received surgical resection of small gastric GISTs could be obtained. Second, further studies should be carried out to investigate the necessity of medication after surgical resection. Third, multicenter randomized controlled studies should be carried out to confirm the benefit of surgical resection of small gastric GISTs compared with conservative patients.