GIST Treatment
Prognosis
Prognostic features of GIST most commonly cited are primary site, size, stage at presentation, mitotic index, cellularity, and mucosal ulceration.1 Based on several large published studies, tumor size and mitotic index have emerged as the most important prognostic features and form the basis of risk assessment (Table 1).2,3
| Risk | Size | Mitotic Count |
|---|---|---|
| Very low | <2 cm | <5/50 HPF |
| Low | 2-5 cm | <5/50 HPF |
| Intermediate | 5 cm 5-10 cm |
6-10/50 HPF <5/50 HPF |
| High | >5 cm >10 cm Any size |
>5/50 HPF Any mitotic rate >10/50 HPF |
HPF, high-power field. Reprinted with permission from Fletcher C et al. Hum Pathol. 2002;33:459-465.3
Although site of origin has been implicated as an additional prognostic factor in several studies (gastric GISTs generally having somewhat better outcomes than primary GISTs in the small intestine),2,4,5a review of approximately 1500 GIST patients over a span of 17 years found that overall survival in GIST was not affected by site of origin or patient gender.6 The authors also found no significant correlation between survival and histologic appearance of the tumor, or between survival and distribution or intensity of staining of CD117. The predictive value of the proposed risk-stratification criteria (tumor size and mitotic index) was confirmed and further refined by inclusion of the Ki-67 proliferation index.
All GISTs have malignant potential: the former classification “benign” is no longer considered appropriate. More than 50% of high-risk tumors will recur or metastasize within 10 years of diagnosis, most within 3 years. Low-risk and very-low-risk GISTs rarely progress (<5%). The prognosis of intermediate-risk tumors is more uncertain.2,3
Clinically aggressive GISTs disseminate throughout the abdomen or metastasize to the liver.7 Lymph node metastases are rare. Evidence from large clinicopathologic studies demonstrates that the presence of liver or peritoneal metastases at presentation is associated with shorter survival.8
Comparisons of low-risk and high-risk GIST frequently show losses from 14q (74%), 22q (53%), and 1p (51%) in both.9-11 High-risk GISTs, however, are distinguished by significantly more chromosomal changes, typically showing gains on chromosomes 5p, 8q, 17q, and 20q, and losses from chromosomes 9p and 13q. Metastatic tumors have more significant chromosomal changes than malignant primary tumors. Chromosomal screening may also identify patients best suited for investigational protocols.
References:
1. Blanke CD, Corless CL. State-of-the art therapy for gastrointestinal stromal tumors. Cancer Invest. 2005;23:274-280.
2. Demetri G, Benjamin R, Blanke CD, et al. NCCN Task Force report: optimal management of patients with gastrointestinal stromal tumor (GIST)—expansion and update of NCCN Clinical Practice Guidelines. J Natl Compr Canc Netw. 2004;2(suppl 1):S1-S26.
3. Fletcher CDM, Berman JJ, Gorstein F, et al. Diagnosis of gastrointestinal stromal tumors: a consensus approach. Hum Pathol. 2002;33:459-465.
4. Emory TS, Sobin LH, Lukes L, Lee DH, O'Leary TJ. Prognosis of gastrointestinal smooth-muscle (stromal) tumors: dependence on anatomic site. Am J Surg Pathol. 1999;23:82-87.
5. Miettinen M, Makhlouf H, Sobin LH, Lasota J. Gastrointestinal stromal tumors of the jejunum and ileum: a clinicopathologic, immunohistochemical, and molecular genetic study of 906 cases before imatinib with long-term follow-up. Am J Surg Pathol. 2006;30:477-489.
6. Nilsson B, Bumming P, Meis-Kindblom JM, et al. Gastrointestinal stromal tumors: The incidence, prevalence, clinical course, and prognostication in the preimatinib mesylate era. Cancer. 2005;103:821-829.
7. Rubin BP. Gastrointestinal stromal tumours: an update. Histopathology. 2006;48:83-96.
8. Miettinen M, El-Rifai W, L HLS, Lasota J. Evaluation of malignancy and prognosis of gastrointestinal stromal tumors: a review. Hum Pathol. 2002;33:478-483.
9. Heinrich MC, Rubin BP, Longley BJ, Fletcher JA. Biology and genetic aspects of gastrointestinal stromal tumors: KIT activation and cytogenetic alterations. Hum Pathol. 2002;33:484-495.
10. Chen Y, Tzeng CC, Liou CP, et al. Biological significance of chromosomal imbalance aberrations in gastrointestinal stromal tumors. J Biomed Sci. 2004;11:65-71.
11. El-Rifai W, Sarlomo-Rikala M, Andersson LC, Knuutila S, Miettinen M. DNA sequence copy number changes in gastrointestinal stromal tumors: tumor progression and prognostic significance. Cancer Res. 2000;60:3899-3903.