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World Journal of Surgical Oncology

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Open Access 01-12-2012 | Research

Significance of EpCAM and TROP2 expression in non-small cell lung cancer

Authors: Min Gyoung Pak, Dong Hoon Shin, Chang Hun Lee, Min Ki Lee

Published in: World Journal of Surgical Oncology | Issue 1/2012

Abstract

Background

The tumor-associated calcium signal transducer (TACSTD) genes, originally designated epithelial cell adhesion molecule (EpCAM) and TROP2, represent true oncogenes. Little is known about EpCAM and TROP2 gene expression in non-small cell lung carcinoma (NSCLC). This study evaluated EpCAM and TROP2 protein expression and clinicopathologic significance in cases of NSCLC.

Methods

Tissue microarray blocks acquired from 164 cases of NSCLC, including 100 cases of adenocarcinoma (AdC) and 64 of squamous cell carcinoma (SCC), were examined by immunohistochemical staining for EpCAM, and TROP2. The results were correlated with clinicopathologic data.

Results

EpCAM and TROP2 were significantly overexpressed in SCC than in AdC (P < 0.01). In AdC, EpCAM overexpression was closely related to sex, histologic grade, pathologic T stage, pathologic N stage, and TNM stage, and TROP2 overexpression was only related to histologic grade (P < 0.05, respectively). In SCC, correlations were evident between EpCAM overexpression and TNM stage (P = 0.01), and between TROP2 overexpression and pathologic T stage (P = 0.02). EpCAM overexpression showed no significance with overall survival in AdC and SCC patients. However, TROP2 overexpression in AdC had a positive influence on overall survival (P = 0.02) and disease-free survival (P = 0.03). In particular, AdC patients with stage II or III showed better overall survival (P = 0.05) and disease-free survival (P = 0.04).

Conclusions

While EpCAM and TROP2 show weak and non-complete membranous staining in normal bronchial epithelium and pneumocyte, their complete membranous expression in carcinoma suggests their role in carcinogenesis. EpCAM and TROP2 were more frequently overexpressed in SCC. EpCAM overexpression had no prognostic value in this study, but TROP2 overexpression showed better survival in AdC patients and might be a better prognostic marker in advanced stage AdC.

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Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D: Global cancer statistics. CA Cancer J Clin. 2011, 61: 69-90. 10.3322/caac.20107.CrossRefPubMed

Piyathilake CJ, Frost AR, Weiss H, Manne U, Heimburger DC, Grizzle WE: The expression of Ep-CAM (17-1A) in squamous cell cancers of the lung. Hum Pathol. 2000, 31: 482-487. 10.1053/hp.2000.6711.CrossRefPubMed

Keedy VL, Temin S, Somerfield MR, Beasley MB, Johnson DH, McShane LM, Milton DT, Strawn JR, Wakelee HA, Giaccone G: American Society of Clinical Oncology provisional clinical opinion: epidermal growth factor receptor (EGFR) mutation testing for patients with advanced non-small-cell lung cancer considering first-line EGFR tyrosine kinase inhibitor therapy. J Clin Oncol. 2011, 29: 2121-2127. 10.1200/JCO.2010.31.8923.CrossRefPubMed

Wenqi D, Li W, Shanshan C, Bei C, Yafei Z, Feihu B, Jie L, Daiming F: EpCAM is overexpressed in gastric cancer and its downregulation suppresses proliferation of gastric cancer. J Cancer Res Clin Oncol. 2009, 135: 1277-1285. 10.1007/s00432-009-0569-5.CrossRefPubMed

Cubas R, Li M, Chen C, Yao Q: Trop2: a possible therapeutic target for late stage epithelial carcinomas. Biochim Biophys Acta. 2009, 1796: 309-314.PubMed

Went PT, Lugli A, Meier S, Bundi M, Mirlacher M, Sauter G, Dirnhofer S: Frequent EpCam protein expression in human carcinomas. Hum Pathol. 2004, 35: 122-128. 10.1016/j.humpath.2003.08.026.CrossRefPubMed

Baeuerle PA, Gires O: EpCAM (CD326) finding its role in cancer. Br J Cancer. 2007, 96: 417-423. 10.1038/sj.bjc.6603494.PubMedCentralCrossRefPubMed

Went P, Dirnhofer S, Salvisberg T, Amin MB, Lim SD, Diener PA, Moch H: Expression of epithelial cell adhesion molecule (EpCam) in renal epithelial tumors. Am J Surg Pathol. 2005, 29: 83-88. 10.1097/01.pas.0000.146028.70868.7a.CrossRefPubMed

Spizzo G, Went P, Dirnhofer S, Obrist P, Simon R, Spichtin H, Maurer R, Metzger U, von Castelberg B, Bart R, Stopatschinskaya S, Kochli OR, Haas P, Mross F, Zuber M, Dietrich H, Bischoff S, Mirlacher M, Sauter G, Gastl G: High Ep-CAM expression is associated with poor prognosis in node-positive breast cancer. Breast Cancer Res Treat. 2004, 86: 207-213. 10.1023/B:BREA.0000036787.59816.01.CrossRefPubMed

10.

Ohmachi T, Tanaka F, Mimori K, Inoue H, Yanaga K, Mori M: Clinical significance of TROP2 expression in colorectal cancer. Clin Cancer Res. 2006, 12: 3057-3063. 10.1158/1078-0432.CCR-05-1961.CrossRefPubMed

11.

Fong D, Spizzo G, Gostner JM, Gastl G, Moser P, Krammel C, Gerhard S, Rasse M, Laimer K: TROP2: a novel prognostic marker in squamous cell carcinoma of the oral cavity. Mod Pathol. 2008, 21: 186-191.PubMed

12.

Nishio M, Koshikawa T, Yatabe Y, Kuroishi T, Suyama M, Nagatake M, Sugiura T, Ariyoshi Y, Mitsudomi T, Takahashi T: Prognostic significance of cyclin D1 and retinoblastoma expression in combination with p53 abnormalities in primary, resected non-small cell lung cancers. Clin Cancer Res. 1997, 3: 1051-1058.PubMed

13.

Kobayashi H, Minami Y, Anami Y, Kondou Y, Iijima T, Kano J, Morishita Y, Tsuta K, Hayashi S, Noguchi M: Expression of the GA733 gene family and its relationship to prognosis in pulmonary adenocarcinoma. Virchows Arch. 2010, 457: 69-76. 10.1007/s00428-010-0930-8.CrossRefPubMed

14.

Cubas R, Zhang S, Li M, Chen C, Yao Q: Trop2 expression contributes to tumor pathogenesis by activating the ERK MAPK pathway. Mol Cancer. 2010, 9: 253-265. 10.1186/1476-4598-9-253.PubMedCentralCrossRefPubMed

15.

El Sewedy T, Fornaro M, Alberti S: Cloning of the murine TROP2 gene: conservation of a PIP2-binding sequence in the cytoplasmic domain of TROP-2. Int J Cancer. 1998, 75: 324-330. 10.1002/(SICI)1097-0215(19980119)75:2<324::AID-IJC24>3.0.CO;2-B.CrossRefPubMed

16.

Fornaro M, Dell'Arciprete R, Stella M, Bucci C, Nutini M, Capri MG, Alberti S: Cloning of the gene encoding Trop-2, a cell-surface glycoprotein expressed by human carcinomas. Int J Cancer. 1995, 62: 610-618. 10.1002/ijc.2910620520.CrossRefPubMed

17.

Nakatsukasa M, Kawasaki S, Yamasaki K, Fukuoka H, Matsuda A, Tsujikawa M, Tanioka H, Nagata-Takaoka M, Hamuro J, Kinoshita S: Tumor-associated calcium signal transducer 2 is required for the proper subcellular localization of claudin 1 and 7: implications in the pathogenesis of gelatinous drop-like corneal dystrophy. Am J Pathol. 2010, 177: 1344-1355. 10.2353/ajpath.2010.100149.PubMedCentralCrossRefPubMed

Title: Significance of EpCAM and TROP2 expression in non-small cell lung cancer
Authors: Min Gyoung Pak
Dong Hoon Shin
Chang Hun Lee
Min Ki Lee
Publication date: 01-12-2012
Publisher: BioMed Central
Published in: World Journal of Surgical Oncology / Issue 1/2012
Electronic ISSN: 1477-7819
DOI: https://doi.org/10.1186/1477-7819-10-53

At a glance: The STEP trials

Springer Medicine

Significance of EpCAM and TROP2 expression in non-small cell lung cancer

Abstract

Background

Methods

Results

Conclusions

At a glance: The STEP trials

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

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