GIST is not one disease, but in fact a family of diseases. In addition to the “adult” form of GIST, there is a pediatric form, and several familial (inherited) forms. A number of mutations exist (KIT, PDGFRA, SDH, NF1, etc.), some forms of the disease have no known mutation, and new mutations will most likely be found in the future. Regardless of what form of the disease a patient has, learning as much as they can about it is essential. Below you’ll find a great deal of information to help get you started.
Understanding GIST Sections:
Gastrointestinal stromal tumors (GISTs) belong to a group of cancers called soft tissue sarcomas. Sarcomas are a rare type of cancer that can occur in connective tissues, bones, muscles, fat, nerves, blood vessels, and cartilage. Sarcomas are derived from the general class of cells known as “mesenchymal cells”. In contrast, most of the “common” cancers, such as lung cancer, skin cancer, and prostate cancer, are derived from a different type of cell, known as “epithelial cells”, the cells which line the body’s many surfaces. Why does this distinction matter? Because carcinomas and sarcomas behave very differently and are treated differently. Sarcomas are much less common than carcinomas. As a result, there are relatively few oncologists who specialize in treating sarcomas.
It is estimated that, in the United States, between 3,000 and 5,000 people each year develop GISTs. Approximately 80-85% of GISTs are limited to a single site at the time of diagnosis; only 15-20% are metastatic at the time of diagnosis.
About 40-70% of GISTs arise from the stomach, 20-40% arise from the small intestine, and 5-15% from the colon and rectum. GISTs can also be found in the esophagus (<5%). Sometimes GISTs develop outside the intestinal tract in the abdominal cavity. These are called eGISTs.
GIST often spreads from the original (primary) site to distant locations. If this happens, these tumors are called metastases (or simply, “mets”). If GIST tumors metastasize they usually travel to the liver, or the peritoneum. Metastases to the lymph-nodes and lungs are rare, but do occur.
When GIST spreads to the liver, the liver tumors are GIST tumors, not liver cancer. GIST metastases in the liver are still derived from GIST cells and must be treated like GIST cells. Liver cancer is a completely different cancer that starts in the liver.
GIST tumors often grow quite large before they are discovered and primary tumors often produce few symptoms. Metastatic tumors can be quite numerous. GISTs are often discovered during emergency surgery for unexpected perforation of the gastrointestinal tract and consequent bleeding. When GIST tumors are first discovered, the most common symptoms are:
- Vague abdominal discomfort or pain.
- Presence of a palpable abdominal mass.
- Feeling of abdominal fullness.
- Secondary symptoms resulting from tumor bleeding and associated anemia.
A Brief History of GIST Cancer:
Although the term “GIST” was first used in 1983 (by Mazur and Clark), the 1998 discovery by Hirota that GIST tumors can contain mutations in the c-kit gene marked the beginning of a new understanding and reclassification of sarcomas of the GI tract. Prior to the year 2000, GISTs were previously classified as one of many types of soft tissue sarcoma (STS) including tumors of smooth-muscle origin (most commonly leiomyosarcoma, and also leiomyoma or leiomyoblastoma) and of neural-crest origin (eg, schwannoma, or nerve sheath tumor). Most tumors previously diagnosed as Gastrointestinal Autonomic Nerve Tumors (GANTs) are also now classified as GISTs and contain essentially the identical KIT mutations as GIST. What establishes GIST as a separate diagnoses from these other soft tissue sarcomas in not just the description of where the tumor is located, but also the additional factor that it is KIT (CD117-positive (although a small percentage of GISTs are KIT-negative). Most GIST patients are also CD34 positive and desmin negative.
KIT-positive? Desmin-negative? What does that mean?
Well, one of the best ways to identify the cancer cell type (aside from just looking at the cells under a microscope) is to determine the proteins that the cell makes. Specialized tests allow the pathologist to do this, usually by determining whether the cell will bind antibodies against the protein of interest. So, “KIT-positive” means that the cell makes the protein “KIT”; desmin-negative means that the cell does not makes the protein “desmin”.
With the development of new effective therapies for GIST, it is vitally important that patients with soft tissue sarcomas of the GI tract have their tumor slides tested for KIT (CD117) by a pathologist experienced with GIST and KIT. Some patients with pathology reports that were done prior to 2001 may think they have leiomyosarcoma, leiomyoma, leiomyoblastoma, or GANT when in fact their pathology slides were never tested for KIT and they may have GIST.
GISTs were previously thought to arise from smooth muscle cells of the GI tract. The discovery that GISTs express the KIT protein helped establish that GISTs do not originate from smooth muscle. The current thinking is that GIST tumors arise either from stem cells that differentiate towards Interstitial Cells of Cajal or directly from Interstitial Cells of Cajal (ICCs). The Interstitial Cells of Cajal are the pacemaker cells of the GI tract, (they are named after a great Spanish biologist and microscopist named Cajal; pronounced “ca-hal”) they stimulate the movement (contractions) of the GI tract. These movements (‘peristalsis”) are the waves of contraction which force the digested food through the gut.
Life Fest 2012 – GIST: From Pathology Puzzle to Targeted Therapy
GIST Cancer Research Is Continually Changing:
GIST research and even GIST clinical practice is moving very quickly. The information presented on this website is believed to be accurate. However, the authors are not medical professionals and the information presented should not be used as a substitute for consultation with a doctor that is experienced with GIST.
No one can take the place of an experienced GIST team of doctors. This may include a Pathologist, Oncologist, and a Surgeon. GIST is such a rare type of cancer that few doctors have much experience in treating it. The hospitals with top sarcoma treatment centers are likely to have more experience with GIST. This is especially true with the hospitals that conducted or are conducting clinical trials with Gleevec and Sutent. They have seen many more GIST patients and are more familiar with their unique needs, with treatment options, managing side effects, monitoring considerations, and what to do if the initial treatment fails.
The Impact of Targeted Therapy:
The introduction of the drug Gleevec for the treatment of GIST has sparked a tremendous amount of interest and research. Gleevec is a molecularly targeted drug that is both more effective and has fewer side effects than traditional chemotherapy. This area of research is very fast moving so recent information is important. Because of this, we have tried to provide a date for key information provided. Such dates will appear in the text where appropriate and will be formatted similar to this: (date of comment: February, 2005).
Sutent is another targeted therapy that was approved in 2006 for GIST that is resistant to Gleevec or for patients that can’t tolerate Gleevec.
Stivarga was approved on February 25th, 2013 in the United States as third-line therapy for GIST. Together, Gleevec, Sutent and Stivarga represent the main drug therapies for advanced GIST.