Immunohistochemical Detection of Lymph Nodes Micrometastases in Patients of Pathologic Stage I Non-small-cell Lung Cancer

병리적 병기 1기의 비소세포폐암 환자에서 면역조직화학염색에 의한 림프절 미세전이 관찰

  • Ryu, Jeong-Seon (Department of Internal Medicine, College of Medicine, Inha University) ;
  • Han, Hye-Seung (Department of Pathology, College of Medicine, Konkuk University) ;
  • Kim, Min-Ji (Department of Internal Medicine, College of Medicine, Inha University) ;
  • Kwak, Seung-Min (Department of Internal Medicine, College of Medicine, Inha University) ;
  • Cho, Jae-Hwa (Department of Internal Medicine, College of Medicine, Inha University) ;
  • Yoon, Yong-Han (Department of Chest Surgery, College of Medicine, Inha University) ;
  • Lee, Hong-Lyeol (Department of Internal Medicine, College of Medicine, Inha University) ;
  • Chu, Young-Chae (Department of Pathology, College of Medicine, Inha University) ;
  • Kim, Kwang-Ho (Department of Chest Surgery, College of Medicine, Inha University)
  • 류정선 (인하대학교 의과대학 내과학교실) ;
  • 한혜승 (건국대학교 의과대학 병리학교실) ;
  • 김민지 (인하대학교 의과대학 내과학교실) ;
  • 곽승민 (인하대학교 의과대학 내과학교실) ;
  • 조재화 (인하대학교 의과대학 내과학교실) ;
  • 윤용한 (인하대학교 의과대학 흉부외과학교실) ;
  • 이홍렬 (인하대학교 의과대학 내과학교실) ;
  • 주영채 (인하대학교 의과대학 병리학교실) ;
  • 김광호 (인하대학교 의과대학 흉부외과학교실)
  • Received : 2004.03.15
  • Accepted : 2004.08.16
  • Published : 2004.10.30

Abstract

Background : To evaluate the frequency and clinical significance of lymph node micrometastasis in patients of non-small-cell lung cancer pathologically staged to be T1-2,N0. Method : From consecutive 29 patients of non-small-cell lung cancer who received curative operation and routine systemic nodal dissection, we immunohistochemically examined 806 lymph nodes from mediastinal, hilar and peribronchial lesion. All slides were stained with hematoxylin and eosin staining for one section and with cytokeratin AE1/AE3 antibody for another consecutive section of same lymph node to find out micrometastasis. Results : In 806 lymph nodes examined, no tumor cell was seen on hematoxylin and eosin staining and micrometastic foci were shown to be on 0.37%(3) of 806 lymph nodes, in which were upper paratracheal, interlobar and peribronchial lymph node. These three positive stains constitute 10.3%(3) of the 29 patients with non-small-cell lung cancer. Nine patients died from disease progression(4), postoperative complication(3) and concomitant diseases(2). The four patients with disease progression did not show evidence of micrometastasis on their lymph node examination. Conclusion : The frequency of lymph node micrometastasis was in 0.37% of 806 lymph nodes examined. The study results might suggested that routine analysis of micrometastasis on the lymph node didn't give any clinical implication on patients with non-small-cell lung cancer.

연구 배경 : 병리적 병기 I기의 비소세포 폐암 환자를 대상으로 림프절 미세 전이의 빈도와 임상적 의의를 알아보고자 연구를 하였다. 방 법 : 수술적 절제를 시행한 29예의 환자에서 총 806개의 파라핀 포매 상태로 보관된 종격동 림프절을 이용하였다. 미세 전이를 확인하기 위하여 림프절 파라핀 불럭으로 2개의 절편을 만들었고 첫 번째 절편은 H & E 염색을, 두 번째 절편은 cytokeratin AE1/AE3 항체를 이용하여 암세포의 미세 전이를 확인하고자 면역 조직화학 염색을 하였다. 결 과 : 대상 환자의 병리적 병기 IA는 10예 이었고 IB는 19예이었다. 면역 조직화학 염색을 시행한 파라핀 블록 수는 총 246개이었고 림프절 수는 총 806개이었다. H & E 염색으로 총 806개의 림프절을 관찰하였으나 암세포의 미세 전이는 관찰되지 않았다. Cytokeratin AE1/AE3 항체를 이용한 면역 조직화학 염색에서 총 806개의 림프절 중 3개(0.37%)에서 관찰되었다. 대상 환자의 평균 관찰 기간은 34.2개월이었고 관찰 기간 중 9예에서 사망이 관찰되었다. 사망 원인은 폐암 진행: 4예, 수술 후 합병증: 3예, 동반 질환: 2예 이었다. 질병의 진행으로 사망한 환자 모두에서 림프절 미세 전이 소견이 관찰되지 않았으며, 림프절 미세 전이가 관찰된 3예의 환자 모두 생존 중이다. 결 론 : 림프절 미세 전이를 발견을 위한 면역 조직화학 염색은 시행한 806개의 림프절중 0.37%에서만 미세전이가 관찰되어 임상적 상용에 어려움이 있을 것으로 생각된다.

Keywords

References

  1. Jiao X, Krasna MJ. Clinical Significance of Micrometastasis in Lung and Esophageal Cancer: A New Paradigm in Thoracic Oncology. Ann Thorac Surg2002;74:278-84
  2. Tanaka F, Miyahara R, Ohtake Y, Yanagihara K, Fukuse T, Hitomi S, et al. Advantage of postoperative oral administration of UFT(tegafur and uracil) for completely resected p-stage I-IIIa nonsmall cell lung cancer(NSCLC). Eur J Cardiothorac Surg 1998;14(3):256-62
  3. Endo C, Saito Y, Iwanami H, Tsushima T, Imai T, Kawamura M, et al. A randomized trial of postoperative UFT therapy in p stage I, II non-small cell lung cancer: North-east Japan Study Group for Lung Cancer Surgery. Lung Cancer 2003;40(2):181-6
  4. Arriagada R, Bergman B, Dunant A, Le Chevalier T, Pignon JP, Vansteenkiste J, et al. Cisplatin-based adjuvant chemotherapy in patients with completely resected non-small-cell lung cancer. N Engl J Med 2004;22;350(4):351-60
  5. Dobashi K, Sugio K, Osaki T, Oka T, Yasumoto K. Micrometastatic p53-positive cells in the lymph nodes of non-small-cell lung cancer: prognostic significance.J Thorac Cardiovasc Surg 1997;114:339-46
  6. Betz C, Papadopoulos T, Buchwald J, Dammrich J, Muller-Hermelink HK. Surfactant protein gene expression in metastatic and micrometastatic pulmonary adenocarcinomas and other non-small cell lung carcinomas: detection by reverse transcriptasepolymerase chain reaction. Cancer Res 1995;55:4283-6
  7. Salerno CT, Frizelle S, Niehans GA, Ho SB, Jakkula M, Kratzke RA, et al. Detection of occult micrometastases in non-small cell lung carcinoma by reverse transcriptase-polymerase chain reaction. Chest 1998;113:1526-32
  8. Iwao K, Watanabe T, Fujiwara Y, Takami K, Kodama K, Higashiyama M, et al. Isolation of a novel human lung-specific gene, LUNX, a potential molecularmarker for detection of micrometastasis in nonsmall-cell lung cancer. Int J Cancer 2001;91:433-7
  9. Maruyama R, Sugio K, Fukuyama Y, Hamatake M, Sakada T, Saitoh G, et al. Evaluation of p53 alterations in occult lymph node metastases. J Surg Oncol 2000;73:143-7
  10. Kawano R, Hata E, Ikeda S, Sakaguchi H. Micrometastasis to lymph nodes in stage I left lung cancer patients. Ann Thorac Surg 2002;73(5):1558-62
  11. Ohta Y, Nozawa H, Tanaka Y, Oda M, Watanabe Y. Increased vascular endothelial growth factor and vascular endothelial growth factor-c and decreasednm23 expression associated with microdissemination in the lymph nodes in stage I non-small cell lung cancer. J Thorac Cardiovasc Surg 2000;119:804-13
  12. Hashimoto T, Kobayashi Y, Ishikawa Y, Tsuchiya S, Okumura S, Nakagawa K, et al. Prognostic value of genetically diagnosed lymph node micrometastasis innon-small cell lung carcinoma cases. Cancer Res 2000;60:6472-8
  13. Goldstein NS, Mani A, Chmielewski G, Welsh R, Pursel S. Immunohistochemically detected micrometastases in peribronchial and mediastinal lymph nodes from patients with T1, N0, M0 pulmonary adenocarcinomas. Am J Surg Pathol 2000;24:274-9
  14. Gu CD, Osaki T, Oyama T, Inoue M, Kodate M, Dobashi K, et al. Detection of micrometastatic tumor cells in pN0 lymph nodes of patients with completelyresected nonsmall cell lung cancer: impact on recurrence and Survival. Ann Surg 2002;235:133-9
  15. Chen ZL, Perez S, Holmes EC, Wang HJ, Coulson WF, Wen DR, et al. Frequency and distribution of occult micrometastases in lymph nodes of patientswith non-small-cell lung carcinoma. J Natl Cancer Inst 1993;85:493-8
  16. Nicholson AG, Graham AN, Pezzella F, Agneta G, Goldstraw P, Pastorino U. Does the use of immunhistochemistry to identify micrometastases provideuseful information in the staging of node-negative non-small cell lung carcinomas? Lung Cancer 1997;18:231-40
  17. Mountain CF. Revisions in the International System for Staging Lung Cancer. Chest 1997;111:1710-7
  18. Prognostic importance of axillary lymph node metastases from breast cancers. International(Ludwig) Breast Cancer Study Group. Lancet 1990;335:1565-8