Expression of L1 protein correlates with cluster of differentiation 24 and integrin β1 expression in gastrointestinal stromal tumors

Du,Yue; Zhang,Haihong; Jiang,Zhongmin; Huang,Guowei; Lu,Wenli; Wang,Hesheng

doi:10.3892/ol.2015.3096

Expression of L1 protein correlates with cluster of differentiation 24 and integrin β1 expression in gastrointestinal stromal tumors

Authors:
- Yue Du
- Haihong Zhang
- Zhongmin Jiang
- Guowei Huang
- Wenli Lu
- Hesheng Wang
View Affiliations

Affiliations: Department of Public Health, Tianjin Medical University, Tianjin 300070, P.R. China, Department of Pathology, Tianjin Fifth Central Hospital, Tianjin 300450, P.R. China
Published online on: April 2, 2015 https://doi.org/10.3892/ol.2015.3096
Pages: 2595-2602

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

The present study examined 66 cases of gastrointestinal stromal tumors (GISTs), 20 cases of smooth muscle tumors, 20 cases of schwannomas and 20 cases of normal gastric tissues in order to analyze the expression of L1, cluster of differentiation (CD)24 and integrin β1 by immunohistochemical staining. Patients were subjected to follow‑up, and survival data were evaluated. L1 expression was detected in 57.6% of GIST cases; this was a significantly higher percentage compared with that found in the smooth muscle tumor cases or the normal control group. CD24 and integrin β1 were also expressed at significantly higher levels in the GIST cases than in the normal control group, although no significant difference was found in the expression levels of these proteins in smooth muscle tumor or schwannoma cases. These higher levels of L1 and integrin β1 expression were associated with an increased risk of invasive GIST, and were significantly positively correlated with Ki‑67 expression. CD24 expression was not associated with the risk of GIST invasion or Ki‑67 expression. There were positive correlations between L1, CD24 and integrin β1 expression; however, these had no significant association with patient survival. Therefore, L1 alone or in conjunction with CD24 (L1 + CD24), or integrin β1 (L1 + integrin β1) can be considered a valuable indicator for the differential diagnosis of GIST. Furthermore, L1 and integrin β1 can be used alone or in combination to evaluate the biological behavior of GISTs. Future studies are required to evaluate the prognostic value of these markers.

View Figures

View References

1	Mazur MT and Clark HB: Gastric stromal tumors. Reappraisal of histogenesis. Am J Surg Pathol. 7:507–519. 1983. View Article : Google Scholar : PubMed/NCBI
2	Corless CL, Barnett CM and Heinrich MC: Gastrointestinal stromal tumours: origin and molecular oncology. Nat Rev Cancer. 11:865–878. 2011.PubMed/NCBI
3	Hamilton SR and Aaltonen LA: Mesenchymal tumours of the stomachWorld Health Organization Classification of Tumours. Pathology and Genetics of Tumours of the Digestive System. IARC Press; Lyon: pp. 62–65. 2003
4	Kiśluk J, Gryko M, Guzińska-Ustymowicz K, et al: Immunohistochemical diagnosis of gastrointestinal stromal tumors-an analysis of 80 cases from 2004 to 2010. Adv Clin Exp Med. 22:33–39. 2013.PubMed/NCBI
5	Bülbül Doğusoy G: Turkish GIST Working Group: Gastrointestinal stromal tumors: A multicenter study of 1160 Turkish cases. Turk J Gastroenterol. 23:203–211. 2012.PubMed/NCBI
6	Montgomery E, Torbenson MS, Kaushal M, et al: Beta-catenin immunohistochemistry separates mesenteric fibromatosis from gastrointestinal stromal tumor and sclerosing mesenteritis. Am J Surg Pathol. 26:1296–1301. 2002. View Article : Google Scholar : PubMed/NCBI
7	Sugiyama T: Progress in new diagnosis and therapeutic strategy for gastrointestinal malignancy: focus on new molecular-targeted treatments. Digestion. 91:7–12. 2015.PubMed/NCBI
8	Miettinen M and Lasota J: Gastrointestinal stromal tumors. Gastroenterol Clin North Am. 42:399–415. 2013. View Article : Google Scholar : PubMed/NCBI
9	Patel S: Exploring novel therapeutic targets in GIST: focus on the PI3K/Akt/mTOR pathway. Curr Oncol Rep. 15:386–395. 2013. View Article : Google Scholar : PubMed/NCBI
10	Le Cesne A and Blay JY: Medical therapy of GIST; from palliative to curative treatment. Bull Acad Natl Med. 196:861–874. 2012.[(In French)]. PubMed/NCBI
11	Emile JF: Histology and molecular biology of GIST. Bull Acad Natl Med. 196:835–844. 2012.[(In French)]. PubMed/NCBI
12	Fletcher CD, Beman JJ, Corless C, et al: Diagnosis of gastrointestinal stromal tumors: A consensus approach. Hum Pathol. 33:459–465. 2002. View Article : Google Scholar : PubMed/NCBI
13	Bareck E, Ba-Ssalamah A, Brodowicz T, et al: Austrian representatives of Medical and Surgical Oncology, Pathology, Radiology, Nuclear Medicine, Gastroenterology, and Laboratory Medicine: Gastrointestinal stromal tumors: diagnosis, therapy and follow-up care in Austria. Wien Med Wochenschr. 163:137–152. 2013. View Article : Google Scholar : PubMed/NCBI
14	Rajendra R, Pollack SM and Jones RL: Management of gastrointestinal stromal tumors. Future Oncol. 9:193–206. 2013. View Article : Google Scholar : PubMed/NCBI
15	Figge C, Loers G, Schachner M and Tilling T: Neurite outgrowth triggered by the cell adhesion molecule L1 requires activation and inactivation of the cytoskeletal protein cofilin. Mol Cell Neurosci. 49:196–204. 2012. View Article : Google Scholar : PubMed/NCBI
16	Siesser PF and Maness PF: L1 cell adhesion molecules as regulators of tumor cell invasiveness. Cell Adh Migr. 3:275–277. 2009. View Article : Google Scholar : PubMed/NCBI
17	Tischler V, Pfeifer M, Hausladen S, et al: L1CAM protein expression is associated with poor prognosis in non-small cell lung cancer. Mol Cancer. 10:1272011. View Article : Google Scholar : PubMed/NCBI
18	Lieberoth A, Splittstoesser F, Katagihallimath N, et al: Lewis(x) and alpha2,3-sialyl glycans and their receptors TAG-1, Contactin, and L1 mediate CD24-dependent neurite outgrowth. J Neurosci. 29:6677–6690. 2009. View Article : Google Scholar : PubMed/NCBI
19	Zhan P, Liu L, Liu B and Mao XG: Expression of integrin β1 and its significance in squamous cell carcinoma of the cervix. Mol Med Rep. 9:2473–2478. 2014.PubMed/NCBI
20	Hirota S, Isozaki K, Moriyama Y, et al: Gain-of-function mutations of c-kit in human gastrointestinal stromal tumors. Science. 279:577–580. 1998. View Article : Google Scholar : PubMed/NCBI
21	Miettinen M and Lasota J: Gastrointestinal stromal tumors: pathology and prognosis at different sites. Semin Diagn Pathol. 23:70–83. 2006. View Article : Google Scholar : PubMed/NCBI
22	Yi JH, Park BB, Kang JH, et al: Retrospective analysis of extra-gastrointestinal stromal tumors. World J Gastroenterol. 21:1845–1850. 2015. View Article : Google Scholar : PubMed/NCBI
23	Raveh S, Gavert N and Ben-Ze'ev A: L1 cell adhesion molecule (L1CAM) in invasive tumors. Cancer Lett. 282:137–145. 2009. View Article : Google Scholar : PubMed/NCBI
24	Zhang C, Fan Y and Fu L: Research development of L1-CAM (CD171) in human cancer. Zhonghua Bing Li Xue Za Zhi. 42:574–576. 2013.[(In Chinese)]. PubMed/NCBI
25	Kaifi JT, Strelow A, Schurr PG, et al: L1 (CD171) is highly expressed in gastrointestinal stromal tumors. Mod Pathol. 19:399–406. 2006. View Article : Google Scholar : PubMed/NCBI
26	Sagiv E and Arber N: The novel oncogene CD24 and its arising role in the carcinogenesis of the GI tract: from research to therapy. Expert Rev Gastroenterol Hepatol. 2:125–133. 2008. View Article : Google Scholar : PubMed/NCBI
27	Su MC, Hsu C, Kao HL and Jeng YM: CD24 expression is a prognostic factor in intrahepatic cholangiocarcinoma. Cancer Lett. 235:34–39. 2006. View Article : Google Scholar : PubMed/NCBI
28	Jacob J, Bellach J, Grützmann R, et al: Expression of CD24 in adenocarcinomas of the pancreas correlates with higher tumor grades. Pancreatology. 4:454–460. 2004. View Article : Google Scholar : PubMed/NCBI
29	Oh BY, Kim KH, Chung SS, et al: Role of β1-integrin in colorectal cancer: case-control study. Ann Coloproctol. 30:61–70. 2014. View Article : Google Scholar : PubMed/NCBI
30	Chen SY, Lin JS and Yang BC: Modulation of tumor cell stiffness and migration by type IV collagen through direct activation of integrin signaling pathway. Arch Biochem Biophys. 555–556:1–8. 2014. View Article : Google Scholar
31	Hortsch M, Nagaraj K and Mualla R: The L1 family of cell adhesion molecules: a sickening number of mutations and protein functions. Adv Neurobiol. 8:195–229. 2014. View Article : Google Scholar : PubMed/NCBI
32	Jaggupilli A and Elkord E: Significance of CD44 and CD24 as cancer stem cell markers: an enduring ambiguity. Clin Dev Immunol. 2012:7080362012. View Article : Google Scholar : PubMed/NCBI
33	Jahangiri A, Aghi MK and Carbonell WS: β1 integrin: Critical path to antiangiogenic therapy resistance and beyond. Cancer Res. 74:3–7. 2014. View Article : Google Scholar : PubMed/NCBI
34	Liakhovich AV and Aksenov NL: Topography of cell ahesion molecules CD9, CD24, L1 and N-CAM on the surface of neuroblastoma cells studied using chemical cross linking. Tsitologiia. 42:399–403. 2000.PubMed/NCBI
35	Fogel M, Mechtersheimer S, Huszar M, et al: L1 adhesion molecule (CD 171) in development and progression of human malignant melanoma. Cancer Lett. 189:237–247. 2003. View Article : Google Scholar : PubMed/NCBI
36	Gavert N, Conacci-Sorrell M, Gast D, et al: L1, a novel target of β-catenin signaling, transforms cells and is expressed at the invasive front of colon cancers. J Cell Biol. 168:633–642. 2005. View Article : Google Scholar : PubMed/NCBI
37	Moulla A, Miliaras D, Sioga A, et al: The immunohistochemical expression of CD24 and CD171 adhesion molecules in borderline ovarian tumors. Pol J Pathol. 64:180–184. 2013. View Article : Google Scholar : PubMed/NCBI
38	Baumann P, Cremers N, Kroese F, et al: CD24 expression causes the acquisition of multiple cellular properties associated with tumor growth and metastasis. Cancer Res. 65:10783–10793. 2005. View Article : Google Scholar : PubMed/NCBI
39	Kleene R, Yang H, Kutsche M and Schachner M: The neural recognition molecule L1 is a sialic acid-binding lectin for CD24, which induces promotion and inhibition of neurite outgrowth. J Biol Chem. 276:21656–21663. 2001. View Article : Google Scholar : PubMed/NCBI
40	Sammar M, Aigner S and Altevogt P: Heat-stable antigen (mouse CD24) in the brain: dual but distinct interaction with P-selectin and L1. Biochim Biophys Acta. 1337:287–294. 1997. View Article : Google Scholar : PubMed/NCBI
41	Kadmon G, Imhof BA, Altevogt P and Schachner M: Adhesive hierarchy involving the cell adhesion molecules L1, CD24, and alpha 6 integrin in murine neuroblastoma N2A cells. Biochem Biophys Res Commun. 214:94–101. 1995. View Article : Google Scholar : PubMed/NCBI