Gastrointestinal stromal tumor historical perspective

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1];Associate Editor(s)-in-Chief: Akshun Kalia M.B.B.S.[2]

Overview

Prior to the advent and use of electron microscopy, gastrointestinal stromal tumors (GIST) were classified as smooth muscle tumors such as leiomyomas or leiomyosarcomas. In 1983, Mazur and Clark and Schaldenbrand and Appleman in 1984 were the first to describe gastrointestinal stromal tumors as an independent entity of intra-abdominal tumors that were neither carcinomas nor exhibit histologic features of smooth muscle or nerve cells. In 1998, Kindblom et al described the origin of GIST as pluripotential mesenchymal stem cells which were programmed to differentiate into the interstitial cell of Cajal. In 1998 Hirota and others were the first to describe c-kit (proto-oncogene) mutations as the cause of GIST. In 2001, Joensuu was the first to report successful treatment of patients with advanced GIST on molecular-targeted therapy (imatinib).

The historical perspective of gastrointestinal stromal tumors (GIST) is as follow: ^[1]^[2]^[3]

Prior to the advent and use of electron microscopy, gastrointestinal stromal tumors (GIST) were classified as smooth muscle tumors such as leiomyomas or leiomyosarcomas. However, electron microscopy gave little evidence in the favour of smooth muscle cells as the origin of GIST.
In 1980s, the use of immunohistochemistry and immunotyping further suggested that GIST arise from antigens related to neural crest cells.
In 1983, Mazur and Clark and Schaldenbrand and Appleman in 1984 were the first to describe gastrointestinal stromal tumors as an independent entity of intra-abdominal tumors that were neither carcinomas nor exhibit histologic features of smooth muscle or nerve cells.
In 1998, Kindblom et al described the origin of GIST as pluripotential mesenchymal stem cells which were programmed to differentiate into the interstitial cell of Cajal.
Additional studies have shown that interstitial cells of Cajal express KIT and their development depends upon stem cell factor, which is regulated through KIT kinase.
In 1998 Hirota and others were the first to describe c-kit (proto-oncogene) mutations as the cause of GIST.
Recent advances in molecular genetics have to led to classification of GIST based on gene type and development of molecular-targeted therapy.
In 2001, Joensuu was the first to report successful treatment of patients with advanced GIST on molecular-targeted therapy (imatinib).

↑ Kindblom LG, Remotti HE, Aldenborg F, Meis-Kindblom JM (1998). “Gastrointestinal pacemaker cell tumor (GIPACT): gastrointestinal stromal tumors show phenotypic characteristics of the interstitial cells of Cajal”. Am. J. Pathol. 152 (5): 1259–69. PMC 1858579. PMID 9588894.
↑ Hirota S, Isozaki K, Moriyama Y, Hashimoto K, Nishida T, Ishiguro S, Kawano K, Hanada M, Kurata A, Takeda M, Muhammad Tunio G, Matsuzawa Y, Kanakura Y, Shinomura Y, Kitamura Y (1998). “Gain-of-function mutations of c-kit in human gastrointestinal stromal tumors”. Science. 279 (5350): 577–80. PMID 9438854.
↑ Mazur MT, Clark HB (1983). “Gastric stromal tumors. Reappraisal of histogenesis”. Am. J. Surg. Pathol. 7 (6): 507–19. PMID 6625048.