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Annals of Surgical Oncology
Published in: Annals of Surgical Oncology 12/2009

01-12-2009 | Thoracic Oncology

CD98 Expression Is Associated with Poor Prognosis in Resected Non-Small-Cell Lung Cancer with Lymph Node Metastases

Authors: Kyoichi Kaira, MD, PhD, Noboru Oriuchi, MD, PhD, Hisao Imai, MD, Kimihiro Shimizu, MD, PhD, Noriko Yanagitani, MD, PhD, Noriaki Sunaga, MD, PhD, Takeshi Hisada, MD, PhD, Osamu Kawashima, MD, PhD, Yosuke Kamide, MD, Tamotsu Ishizuka, MD, PhD, Yoshikatsu Kanai, MD, PhD, Takashi Nakajima, MD, PhD, Masatomo Mori, MD, PhD

Published in: Annals of Surgical Oncology | Issue 12/2009

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Abstract

Background

The purpose of this study was to evaluate the prognostic value of L-type amino acid transporter 1 (LAT1) and 4F2 heavy chain (CD98) expression in resectable non-small-cell lung cancer (NSCLC) patients with N1 and N2 nodal involvement.

Methods

A total of 220 consecutive patients were retrospectively reviewed. Immunohistochemical expression of LAT1, CD98, Ki-67 labeling index, vascular endothelial growth factor (VEGF), and microvessel density (MVD) was correlated with clinical features and prognosis of patients after complete resection of the tumor.

Results

Positive expression of LAT1 and CD98 was recognized in 60% (132/220) and 47% (103/220), respectively (P = 0.021). A positive rate of LAT1 expression was significantly higher in squamous cell carcinoma (SQC) (91%; 65/71) and large cell carcinoma (LCC) (82%; 9/11) than in adenocarcinoma (AC) (42%; 58/138). Moreover, a positive rate of CD98 expression was also significantly higher in SQC (76%; 54/71) and LCC (73%; 8/11) than in AC (30%; 42/138). LAT1 expression was significantly correlated with CD98, Ki-67 labeling index, VEGF, and MVD. The 5-year survival rates of LAT1-positive and LAT1-negative patients and CD98-positive and CD98-negative patients, were 43% and 48% (P = 0.1043), respectively and 39% and 50% (P = 0.0239), respectively. Multivariate analysis confirmed that positive expression of CD98 was an independent factor for predicting a poor prognosis.

Conclusions

In our limited series, CD98 is a pathological factor that predicts prognosis in resectable adenocarcinoma patients with N2 disease.
Literature
1.
Shottenfeld D. Epidemiology of lung cancer. Philadelphia, PA: Lippincott-Raven; 1996.
2.
Graziano SL. Non-small cell lung cancer: clinical value of new biological predictors. Lung Cancer. 1997;17(Suppl. 1):S37–58.CrossRefPubMed
3.
Mountain CF. Revision in the International System for Staging Lung Cancer. Chest. 1997;11:1710–7.CrossRef
4.
Andre F, Grunenwald D, Pignon JP, et al. Survival of patients with resected N2 non-small-cell lung cancer: evidence for a subclassification and implications. J Clin Oncol. 2000;18:2981–9.PubMed
5.
Leong SS, Rocha Lima CM, Sherman CA, et al. The 1997 International Staging System for non-small cell lung cancer: have all the issues been addressed? Chest. 1999;115:242–8.CrossRefPubMed
6.
Jassem J, Skokowski J, Dziadziuszko R, et al. Results of surgical treatment of non-small cell lung cancer: validation of the new postoperative pathologic TNM classification. J Thorac Cardiovasc Surg. 2000;119:1141–6.CrossRefPubMed
7.
Clinical practice guidelines for the treatment of unresectable non-small cell lung cancer: adopted on May 16, 1997 by the American Society of Clinical Oncology. J Clin Oncol. 1997;15:2996–3018.
8.
Christensen HN. Role of amino acid transport and countertransport in nutrition and metabolism. Physiol Rev. 1990;70:43–77.PubMed
9.
McGivan JD, Pastor-Anglada M. Regulatory and molecular aspects of mammalian amino acid transport. Biochem J. 1994;299:321–34.PubMed
10.
Oxender DL, Christensen HN. Evidence for two types of mediation of neutral amino acid transport in Ehrlich cells. Nature. 1963;197:765–7.CrossRefPubMed
11.
Kanai Y, Segawa H, Miyamoto K, Uchino H, Takeda E, Endou H. Expression cloning and characterization of a transporter for large neutral amino acids activated by the heavy chain of 4F2 antigen (CD98). J Biol Chem. 1998;273:23629–32.CrossRefPubMed
12.
Yanagida O, Kanai Y, Chairoungdua A, et al. Human L-type amino acid transporter 1 (LAT 1): characterization of function and expression in tumor cell lines. Biochim Biophys Acta. 2001;1514:291–302.CrossRefPubMed
13.
Ohkame H, Masuda H, Ishii Y, Kanai Y. Expression of L-type amino acid transporter 1 (LAT1) and 4F2 heavy chain (4F2hc) in liver tumor lesions of rat models. J Surg Oncol. 2001;78:265–71; discussion 271–2.CrossRefPubMed
14.
Kaira K, Oriuchi N, Imai H, et al. Prognostic significance of L-type amino acid transporter 1 expression in resectable stage I-III nonsmall cell lung cancer. Br J Cancer. 2008;98:742–8.CrossRefPubMed
15.
Kaira K, Oriuchi N, Imai H, et al. Expression of L-type amino acid transporter 1 (LAT1) in neuroendocrine tumors of the lung. Pathol Res Pract. 2008;204:553–61.CrossRefPubMed
16.
Kaira K, Oriuchi N, Imai H, et al. L-type amino acid transporter 1 (LAT1) and CD98 expression in the primary site and the metastatic site of human neoplasms. Cancer Sci. 2008;99:3280–6.CrossRef
17.
Nawashiro H, Otani N, Shinomiya N, et al. L-type amino acid transporter 1 as a potential molecular target in human astrocytic tumors. Int J Cancer. 2006;119:484–92.CrossRefPubMed
18.
Chairoungdua A, Segawa H, Kim JY, et al. Identification of an amino acid transporter associated with the cystinuria-related type II membrane glycoprotein. J Biol Chem. 1999;274:28845–8.CrossRefPubMed
19.
Matsuo H, Tsukada S, Nakata T, et al. Expression of a system L neutral amino acid transporter at the blood–brain barrier. Neuroreport. 2000;11:3507–11.CrossRefPubMed
20.
Buck AC, Schirmeister HH, Guhlmann CA, et al. Ki-67 immunostaining in pancreatic cancer and chronic active pancreatitis: does in vivo FDG uptake correlate with proliferative activity? J Nucl Med. 2001;42:721–5.PubMed
21.
Weidner N, Semple JP, Welch WR, Folkman J. Tumor angiogenesis and metastasis-correlation in invasive breast carcinoma. N Engl J Med. 1991;324:1–8.PubMed
22.
Mineo TC, Ambrogi V, Baldi A, et al. Prognostic impact of VEGF, CD31, CD34, and CD105 expression and tumor vessel invasion after radical surgery for IB-IIA non-small cell lung cancer. J Clin Pathol. 2004;57:591–7.CrossRefPubMed
23.
Kaira K, Oriuchi N, Imai H, et al. Prognostic significance of L-type amino acid transporter 1 (LAT1) and 4F2 heavy chain (CD98) expression in stage I pulmonary adenocarcinoma. Lung Cancer. 2009;66:120–6.
24.
Kaira K, Oriuchi N, Imai H, et al. Prognostic significance of L-type amino acid transporter 1 (LAT1) and 4F2 heavy chain (CD98) expression in early stage squamous cell carcinoma of the lung. Cancer Sci. 2009;100:249–54.CrossRef
25.
Imai H, Kaira K, Oriuchi N, et al. L-type amino acid transporter 1 expression is a prognostic marker in patients with surgically resected stage I non-small cell lung cancer. Histopathology. 2009;54:804–13.
26.
Rintoul RC, Buttery RC, Mackinnon AC, et al. Cross-linking CD98 promotes integrin-like signaling and anchorage-independent growth. Mol Biol Cell. 2002;13:2841–52.CrossRefPubMed
27.
Takeuchi H, Kubota T, Kitai R, et al. CD98 immunoreactivity in multinucleated giant cells of glioblastomas: an immunohistochemical double labeling study. Neuropathology. 2008;28:127–31.CrossRefPubMed
28.
Nakanishi K, Ogata S, Matsuo H, et al. Expression of LAT1 predicts risk of progression of transitional cell carcinoma of the upper urinary tract. Virchows Arch. 2007;451:681–90.CrossRefPubMed
29.
Fucks BC, Finger RE, Onan MC, Bode BP. ASCT2 silencing regulates mammalian target-of-rapamycin growth and survival signaling in human hepatoma cells. Am J Physiol Cell Physiol. 2007;293:55–63.CrossRef
30.
Winton T, Livingston R, Johnson D, et al. A prospective randomized trial of adjuvant vinorelbine (VNR) and cisplatin (CIS) in completely resected stage Ib and II non-small cell lung cancer (NSCLC). Intergroup JBR 10. N Engl J Med. 2005;352:2589–97.CrossRefPubMed
31.
Arriagada R, Bergman B, Dunant A, et al. Cisplatin based adjuvant chemotherapy in patients with completely resected non-small cell lung cancer. N Engl J Med. 2004;350:351–60.CrossRefPubMed
32.
Douillard J, Rosell R, De Lena M, et al. Adjuvant vinorelbine plus cisplatin versus observation in patients with completely resected stage IB-IIIA non-small cell lung cancer (Adjuvant Navelbine International Trialist Association[ANITA]):a randomized control trial. Lancet Oncol. 2006;7:719–27.CrossRefPubMed
33.
Kang CH, Ra YJ, Kim YT, et al. The impact of multiple metastatic nodal stations on survival in patients with resectable N1 and N2 nonsmall-cell lung cancer. Ann Thorac Surg. 2008;86:109–7.CrossRefPubMed
34.
Sayar A, Turna A, Kilicgun A, et al. Prognostic significance of surgical-pathologic multiple-station N1 disease in non-small cell carcinoma of the lung. Eur J Cardiothoracic Surg. 2004;25:434–8.CrossRef
35.
Pignon JP, Tribodet H, Scagliotti GV, et al. Lung adjuvant cisplatin evaluation: A pooled analysis by the LACE collaborative group. J Clin Oncol. 2008;26:3552–9.CrossRefPubMed
Metadata
Title
CD98 Expression Is Associated with Poor Prognosis in Resected Non-Small-Cell Lung Cancer with Lymph Node Metastases
Authors
Kyoichi Kaira, MD, PhD
Noboru Oriuchi, MD, PhD
Hisao Imai, MD
Kimihiro Shimizu, MD, PhD
Noriko Yanagitani, MD, PhD
Noriaki Sunaga, MD, PhD
Takeshi Hisada, MD, PhD
Osamu Kawashima, MD, PhD
Yosuke Kamide, MD
Tamotsu Ishizuka, MD, PhD
Yoshikatsu Kanai, MD, PhD
Takashi Nakajima, MD, PhD
Masatomo Mori, MD, PhD
Publication date
01-12-2009
Publisher
Springer-Verlag
Published in
Annals of Surgical Oncology / Issue 12/2009
Print ISSN: 1068-9265
Electronic ISSN: 1534-4681
DOI
https://doi.org/10.1245/s10434-009-0685-0

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