Skip to main content
Erschienen 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

verfasst von: 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

Erschienen in: Annals of Surgical Oncology | Ausgabe 12/2009

Einloggen, um Zugang zu erhalten

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.
Literatur
1.
Zurück zum Zitat Shottenfeld D. Epidemiology of lung cancer. Philadelphia, PA: Lippincott-Raven; 1996. Shottenfeld D. Epidemiology of lung cancer. Philadelphia, PA: Lippincott-Raven; 1996.
2.
Zurück zum Zitat Graziano SL. Non-small cell lung cancer: clinical value of new biological predictors. Lung Cancer. 1997;17(Suppl. 1):S37–58.CrossRefPubMed Graziano SL. Non-small cell lung cancer: clinical value of new biological predictors. Lung Cancer. 1997;17(Suppl. 1):S37–58.CrossRefPubMed
3.
Zurück zum Zitat Mountain CF. Revision in the International System for Staging Lung Cancer. Chest. 1997;11:1710–7.CrossRef Mountain CF. Revision in the International System for Staging Lung Cancer. Chest. 1997;11:1710–7.CrossRef
4.
Zurück zum Zitat 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 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.
Zurück zum Zitat 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 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.
Zurück zum Zitat 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 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.
Zurück zum Zitat 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. 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.
Zurück zum Zitat Christensen HN. Role of amino acid transport and countertransport in nutrition and metabolism. Physiol Rev. 1990;70:43–77.PubMed Christensen HN. Role of amino acid transport and countertransport in nutrition and metabolism. Physiol Rev. 1990;70:43–77.PubMed
9.
Zurück zum Zitat McGivan JD, Pastor-Anglada M. Regulatory and molecular aspects of mammalian amino acid transport. Biochem J. 1994;299:321–34.PubMed McGivan JD, Pastor-Anglada M. Regulatory and molecular aspects of mammalian amino acid transport. Biochem J. 1994;299:321–34.PubMed
10.
Zurück zum Zitat Oxender DL, Christensen HN. Evidence for two types of mediation of neutral amino acid transport in Ehrlich cells. Nature. 1963;197:765–7.CrossRefPubMed 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.
Zurück zum Zitat 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 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.
Zurück zum Zitat 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 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.
Zurück zum Zitat 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 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.
Zurück zum Zitat 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 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.
Zurück zum Zitat 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 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.
Zurück zum Zitat 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 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.
Zurück zum Zitat 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 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.
Zurück zum Zitat 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 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.
Zurück zum Zitat 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 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.
Zurück zum Zitat 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 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.
Zurück zum Zitat 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 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.
Zurück zum Zitat 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 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.
Zurück zum Zitat 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. 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.
Zurück zum Zitat 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 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.
Zurück zum Zitat 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. 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.
Zurück zum Zitat 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 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.
Zurück zum Zitat 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 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.
Zurück zum Zitat 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 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.
Zurück zum Zitat 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 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.
Zurück zum Zitat 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 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.
Zurück zum Zitat 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 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.
Zurück zum Zitat 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 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.
Zurück zum Zitat 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 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.
Zurück zum Zitat 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 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.
Zurück zum Zitat 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 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
Metadaten
Titel
CD98 Expression Is Associated with Poor Prognosis in Resected Non-Small-Cell Lung Cancer with Lymph Node Metastases
verfasst von
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
Publikationsdatum
01.12.2009
Verlag
Springer-Verlag
Erschienen in
Annals of Surgical Oncology / Ausgabe 12/2009
Print ISSN: 1068-9265
Elektronische ISSN: 1534-4681
DOI
https://doi.org/10.1245/s10434-009-0685-0

Weitere Artikel der Ausgabe 12/2009

Annals of Surgical Oncology 12/2009 Zur Ausgabe

Translational Research and Biomarkers

RGS16 Is a Marker for Prognosis in Colorectal Cancer

Wie erfolgreich ist eine Re-Ablation nach Rezidiv?

23.04.2024 Ablationstherapie Nachrichten

Nach der Katheterablation von Vorhofflimmern kommt es bei etwa einem Drittel der Patienten zu Rezidiven, meist binnen eines Jahres. Wie sich spätere Rückfälle auf die Erfolgschancen einer erneuten Ablation auswirken, haben Schweizer Kardiologen erforscht.

Hinter dieser Appendizitis steckte ein Erreger

23.04.2024 Appendizitis Nachrichten

Schmerzen im Unterbauch, aber sonst nicht viel, was auf eine Appendizitis hindeutete: Ein junger Mann hatte Glück, dass trotzdem eine Laparoskopie mit Appendektomie durchgeführt und der Wurmfortsatz histologisch untersucht wurde.

Mehr Schaden als Nutzen durch präoperatives Aussetzen von GLP-1-Agonisten?

23.04.2024 Operationsvorbereitung Nachrichten

Derzeit wird empfohlen, eine Therapie mit GLP-1-Rezeptoragonisten präoperativ zu unterbrechen. Eine neue Studie nährt jedoch Zweifel an der Notwendigkeit der Maßnahme.

Ureterstriktur: Innovative OP-Technik bewährt sich

19.04.2024 EAU 2024 Kongressbericht

Die Ureterstriktur ist eine relativ seltene Komplikation, trotzdem bedarf sie einer differenzierten Versorgung. In komplexen Fällen wird dies durch die roboterassistierte OP-Technik gewährleistet. Erste Resultate ermutigen.

Update Chirurgie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.

S3-Leitlinie „Diagnostik und Therapie des Karpaltunnelsyndroms“

Karpaltunnelsyndrom BDC Leitlinien Webinare
CME: 2 Punkte

Das Karpaltunnelsyndrom ist die häufigste Kompressionsneuropathie peripherer Nerven. Obwohl die Anamnese mit dem nächtlichen Einschlafen der Hand (Brachialgia parästhetica nocturna) sehr typisch ist, ist eine klinisch-neurologische Untersuchung und Elektroneurografie in manchen Fällen auch eine Neurosonografie erforderlich. Im Anfangsstadium sind konservative Maßnahmen (Handgelenksschiene, Ergotherapie) empfehlenswert. Bei nicht Ansprechen der konservativen Therapie oder Auftreten von neurologischen Ausfällen ist eine Dekompression des N. medianus am Karpaltunnel indiziert.

Prof. Dr. med. Gregor Antoniadis
Berufsverband der Deutschen Chirurgie e.V.

S2e-Leitlinie „Distale Radiusfraktur“

Radiusfraktur BDC Leitlinien Webinare
CME: 2 Punkte

Das Webinar beschäftigt sich mit Fragen und Antworten zu Diagnostik und Klassifikation sowie Möglichkeiten des Ausschlusses von Zusatzverletzungen. Die Referenten erläutern, welche Frakturen konservativ behandelt werden können und wie. Das Webinar beantwortet die Frage nach aktuellen operativen Therapiekonzepten: Welcher Zugang, welches Osteosynthesematerial? Auf was muss bei der Nachbehandlung der distalen Radiusfraktur geachtet werden?

PD Dr. med. Oliver Pieske
Dr. med. Benjamin Meyknecht
Berufsverband der Deutschen Chirurgie e.V.

S1-Leitlinie „Empfehlungen zur Therapie der akuten Appendizitis bei Erwachsenen“

Appendizitis BDC Leitlinien Webinare
CME: 2 Punkte

Inhalte des Webinars zur S1-Leitlinie „Empfehlungen zur Therapie der akuten Appendizitis bei Erwachsenen“ sind die Darstellung des Projektes und des Erstellungswegs zur S1-Leitlinie, die Erläuterung der klinischen Relevanz der Klassifikation EAES 2015, die wissenschaftliche Begründung der wichtigsten Empfehlungen und die Darstellung stadiengerechter Therapieoptionen.

Dr. med. Mihailo Andric
Berufsverband der Deutschen Chirurgie e.V.