L1 (CD171) is highly expressed in gastrointestinal stromal tumors

Abstract

The treatment strategy for mesenchymal tumors of the gastrointestinal tract is based upon typing of the tumor. Especially differential diagnosis of gastrointestinal stromal tumors (GISTs) to leiomyomas is crucial for determining radicality of surgery. L1 cell adhesion molecule (CD171) plays an essential role in tumor progression. The aim of this study was to determine expression of L1 in GISTs, smooth muscle tumors, desmoid-type fibromatosis and peripheral nerve sheath tumors (PNSTs). We retrospectively analyzed a total of 129 surgically resected primary tumors or metastases of 72 GISTs, 29 smooth muscle tumors, seven PNSTs and 21 desmoid-type fibromatosis by immunohistochemistry for c-kit, CD34, smooth muscle actin, desmin, vimentin, S-100 and L1 expression. L1 expression was detected in 53 (74%) of 72 GISTs but in none of 29 smooth muscle tumors or 21 desmoid-type fibromatosis (Po0.01 by Fisher's test). In all, four (57%) of seven peripheral nerve sheath tumors were L1-positive. Survival analysis of 55 surgically completely resected GISTs presenting without metastasis at initial diagnosis revealed no tumor-specific death among L1-negative patients (P ¼ 0.13 by log-rank test; median follow-up time 41 months) and one recurrence was observed (P ¼ 0.12). Interestingly high levels of L1 were seen in tumor vascular endothelial cells of smooth muscle tumors and PNSTs, but not in GISTs. Our data show that L1 is highly expressed in GISTs but not in smooth muscle tumors and desmoid-type fibromatosis being important differential diagnoses. The trend towards a reduced survival of L1-positive patients in this study has to be further evaluated in future trials with higher patient numbers.

The adhesion molecule L1 regulates transendothelial migration and trafficking of dendritic cells

“…L1 was absent from normal quiescent vasculature (not depicted), but it was detected on the vessels associated to pathological conditions such as neoplastic or infl ammatory diseases ( Fig. 6 ), confi rming and extending previous observations ( 10,22 ). Because this suggested that the expression of L1 is regulated by tumor-or infl ammatory cell -derived fac- heterophilic binding partners of L1 involved in DC -EC interactions remain elusive, members of the integrin family are suitable candidates.…”

L1 is associated with micrometastatic spread and poor outcome in colorectal cancer

“…15,[35][36][37] On the other hand, epithelial pancreatic adenocarcinomas rarely express L1. 38 However, L1 expression is consistently associated with aggressive clinical behavior in other epithelial tumors like uterine, ovarian or also colon carcinomas.…”

“…2 Expression of L1 was also described in tumor vessels in renal cell carcinomas and smooth muscle tumors and could therefore enhance attachment of tumor cells by homophilic binding. 20,36 A role of L1 in homing of colorectal cancer cells to lymph nodes and bone marrow is probable, especially since L1 undergoing homophilic binding is also expressed in a subset of lymph node leukocytes. 39 However, a correlation does not prove a direct role of L1 in this process.…”

Diagnostic and prognostic markers for gastrointestinal stromal tumors in Norway

“…30 Overexpression of L1 is associated with metastasis in cutaneous malignant melanomas, whereas inactivation of L1 significantly reduces the invasion and migration of melanoma cells. 31 In the work of Keifi et al, 25 L1 was evaluated both as a diagnostic and as a prognostic marker for GIST. Their study included 72 cases, with little information provided about the patient population from which the series was derived.…”