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| Interstitial cells of Cajal as precursors of gastrointestinal stromal tumors |
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| Author(s): Sircar K, Hewlett BR, Huizinga JD, Chorneyko K, Berezin I, Riddell RH |
| Source: AMERICAN JOURNAL OF SURGICAL PATHOLOGY Volume: 23 Issue: 4 Pages: 377-389 Published: APR 1999 |
| Times Cited: 238 References: 39 |
| Abstract: Interstitial cells of Cajal (ICC) are implicated in the regulation of gut peristalsis and are immunostained by antibodies against Kit (CD117), a tyrosine kinase receptor. Most gastrointestinal mesenchymal tumors (GIMTs) are of uncertain histogenesis, although many are CD34-positive. CD34 was found to colocalize with vimentin (Vim) and the Kit-positive networks of cells within and around neural plexi, indicating that ICC can be Vim- and CD34-positive. ICCs appear to be the only Kit+CD34+Vim+ cell in the gut. Formalin-fixed, paraffin-embedded tissues from 43 GIMTs were immunostained for Kit, CD34, Vim, PGP 9.5 (PGP, a neural marker), muscle-specific actin (MSA), and other markers including desmin (Des). Eight tumors were myoid (MSA+Des+Vim-Kit-CD34-), and one was a schwannoma (PGP+S100+Vim+Kit-CD34-), but 34 tumors were of uncertain histogenesis (gastrointestinal stromal tumors, GIST), exhibiting neither a complete myoid nor a schwannian immunophenotype. All 34 were Vim+, and 33/34 were either Kit (n = 30) or CD34 (n = 23) immunoreactive. Of these 34 GIST, 24 were negative for all myoid and neural markers, 6 were PGP+S100-, and 4 were MSA+Des-. The Kit+CD34+Vim+ immunophenotype of GIST suggests that they originate from, or have differentiated into, ICC-like cells; the term ICC tumor (ICCT) is suggested. Kit is a more sensitive marker than CD34 for ICCT, but both are required in tumor identification. All clinically malignant GISTs were pathologically malignant (size, mitoses) but also showed loss of either CD34 or Kit. "Blind" examination of electron micrographs in 10 tumors showed them to be heterogeneous. Some had features seen in normal ICC, but cells could not be positively identified as being adult ICC. GIMT may therefore be classifiable into those with pure myoid, schwannian (or neural) differentiation, but the majority are of ICC origin or show ICC differentiation immunophenotypically (ICCT). |
| Document Type: Article |
| Language: English |
| Reprint Address: Riddell, RH (reprint author), McMaster Univ, Med Ctr, Dept Pathol, Hamilton, ON L8N 3Z5 Canada |
Addresses:
1. McMaster Univ, Med Ctr, Dept Pathol, Hamilton, ON L8N 3Z5 Canada
2. McMaster Univ, Med Ctr, Dept Mol Med, Hamilton, ON L8N 3Z5 Canada
3. McMaster Univ, Med Ctr, Dept Biomed Sci, Hamilton, ON L8N 3Z5 Canada
4. McMaster Univ, Med Ctr, Intestinal Dis Res Program, Hamilton, ON L8N 3Z5 Canada |
| Publisher: LIPPINCOTT WILLIAMS & WILKINS, 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA |
| Subject Category: Pathology; Surgery |
| IDS Number: 183TQ |
| ISSN: 0147-5185 |
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