Clinical Significance of Lymph Node Micrometastasis in Patients with Stage 1 Non-Small Cell Lung Cancer

제1기 비소세포폐암 환자에서 임파절 미세전이와 예후와의 상관관계

  • 최필조 (동아대학교 의과대학 흉뷰외과학교실) ;
  • 노미숙 (동아대학교 의과대학 병리학교실) ;
  • 이재익 (동아대학교 의과대학 흉뷰외과학교실)
  • Published : 2003.05.01

Abstract

Background: The prognostic significance of lymph node micrometastasis in non-small cell lung cancer remains controversial. We therefore investigated the clinicopathologic factors related to lymph node micrometastsis and evaluated the clinical relevance of micrometastasis with regard to recurrence. Material and Method: Five hundred six lymph nodes were obtained from 41 patients with stage 1 non-small ceil lung cancer who underwent curative resection between 1994 and 1998. Immunohistochemical staining using anti-cytokeratin Ab was used to detect micrometastasis in these lymph nodes. Result: Micrometastatic tumor cells were identified in pN0 lymph nodes in 14 (34.1%) of 41 patients. The presence of lymph node micrometastasis was not related to any clinicopathoiogic factor (p) 0.05). The recurrence rate was higher in patients with micrometastasis (57.1%) than in those without (37.0%), but the difference was not significant (p=0.22). Patients with micrometastasis had a lower 5-year recurrence-free survival rate (48.2%) than those without micrometastasis (64.1%), with a borderline significance (p=0.11), The S-year recurrence-free survival rate (25.0%) in the patients with 2 or more micrometastatic lymph nodes was significantly lower than that in the patients with no or single micrometastasis (p=0.02). In multivariate analysis, multiple lymph node micromestasis us was a significant independent predictor of recurrence (p=0.028, Risk ratio=3.568). Conclusion: Immunehistochemical anti-cytokeratin staining was a rapid, sensitive, and easy way of detecting lymph node micrometastasis. The presence of lymph node micrometastasis was not significantly associated with the recurrence, but had a tendency toward a poor prognosis in stage 1 non-small cell lung cancer. Especially, the presence of multiple micrometastatic lymph nodes was a significant and independent predictor of recurrence.

배경: 폐암에서 임파절 전이는 가장 중요한 예후 인자로 알려져 있다. 그러나 임파절에 전이 병소가 없는 제1기 비소세포 폐암의 경우에도 근치적 절제술 후 약 30∼40%의 환자가 종양의 재발이나 원격 전이로 사망하게 된다. 이것은 진단 혹은 수술 당시 이미 국소 임파절이나 다른 장기에 미세전이가 일어났을 가능성을 시사한다. 이에 저자들은 근치적 절제술을 시행한 제1기 비소세포 폐암 환자의 임파절을 면역조직화학 염색하여 임파절 미세전이를 조사하고, 미세전이 여부와 임상양상과의 연관성을 알아보았다. 대상 및 방법: 종격동 및 폐문부 임파절 절제술과 함께 근치적 절제술이 시행된 원발성 폐암 환자 중, 술 후 제1기 비소세포 폐암 환자로 확진된 41명으로부터 절제된 506개의 임파절을 anti-cytokeratin 항체를 이용한 면역조직화학염색법을 이용하여 미세전이 여부를 조사하였다. 결과: 대상환자 총 41명 중 14명(34.1%)에서 임파절 미세전이가 발견되었으며, 미세전이 여부는 여러 임상 병리학적 요소들과 유의한 관련성을 보이지 않았다. 평균 50개월의 추적 기간에 미세전이 양성군의 재발률은 57.1%로 음성군(37.0%)에 비해 높았으나 통계적 유의성은 없었다(p=0.22). 또한 미세전이 양성군의 5년 무병생존율은 48.2%로 64.1%인 음성군에 비해 낮은 경향을 보였지만 한계적 유의성만을 확인할 수 있었다(p=0.11). 그러나 2개 이상의 임파절에서 미세전이가 발견된 환자들의 5년 무병생존율은 25.0%로서 다른 환자들에 비해 통계적으로 유의하게 낮았다(p=0.02). 다변량 분석 결과, 제1기 비소세포 폐암 환자에 있어서 다발성 임파절 미세전이는 독립적인 재발의 예측인자임을 확인할 수 있었다(p=0.028). 결론: 항cytokeratin 항체를 이용한 면역조직화학염색을 통하여 신속하고 용이하게 임파절 미세전이를 발견할 수 있었다. 제1기 비소세포 폐암 환자에서 임파절 미세전이가 예후에 나쁜 영향을 미침을 통계적으로 유의하게 입증하지는 못하였지만 그 경향은 밝혀 낼 수 있었고, 특히 다발성 임파절 미제전이가 재발에 영향을 주는 독립적인 예후인자임을 밝혀낼 수 있었다.

Keywords

References

  1. J Thorac Cardiovasc Surg v.96 Prognosis and survival in resected lung carcinoma based on the new international staging system Naruke,T.;Goya,T.;Tsuchiya,R.;Suemasu,K.
  2. CA Cancer J Clin v.51 Cancer statics,2001 Greenlee,R.T.;Hill-Harmon,M.B.;Murray,T.;Thun,M. https://doi.org/10.3322/canjclin.51.1.15
  3. Lancet v.345 Genetic diagnosis of lymph-node metastasis in colorectal cancer Hayashi,N.;Ito,I.;Nakamura,Y.(et al) https://doi.org/10.1016/S0140-6736(95)90922-2
  4. Br J Cancer v.55 Micrometastasis to axillary lymph nodes from carcinoma of breast:detection by immunohistochemistry and porgnostic significance Trojani,M.; de Mascarel I.;Bonichon,F.;Coindre,J.M.;Delsol,G. https://doi.org/10.1038/bjc.1987.59
  5. J Thorac Cardiovasc Surg v.114 Relationship between early recurrence and micrometastases in lympn nodes of patients with stage Ⅰ non-small-cell lung cancer Maruyama,R.;Sugio,K.;Mitsudomi,T.(et al) https://doi.org/10.1016/S0022-5223(97)70041-2
  6. Ann Srug v.173 Significance of axillary macrometastasis and micrometastasis in mammary cancer Huvos,A.G.;Hutter,R.V.;Berg,J.W. https://doi.org/10.1097/00000658-197101000-00006
  7. J Natl Cancer Inst v.91 Detection and clinical relevance of micrometastatic disease Pantel,K.;Cote,R.;Fodstad,O. https://doi.org/10.1093/jnci/91.13.1113
  8. Lancet v.347 Prognostic significance of isolated tumour cells in bone marrow of patients with non-small cell carcinomas without overt metastases Pantel,K.;Izibicki,J.R.;Passlick,B.(et al) https://doi.org/10.1016/S0140-6736(96)91203-9
  9. Ann Thorac Surg v.64 Micrometastatic tumor cells in the bone marrow of patients with non-small cell lung cancer Ohgami,A.;Mitsudomi,T.;Sugio,K.(et al) https://doi.org/10.1016/S0003-4975(97)00543-2
  10. Cell v.31 The catalog of human cytokeratins: pattern of expression in normal epithelia,tumors and cultured cells Moll,R.;Franke,W.W.;Schiller,D.L.;Geiger,B.;Krepler,R. https://doi.org/10.1016/0092-8674(82)90400-7
  11. Jap J Cancer Res v.87 Detection of gastric cancer micrometastases in lymph nodes by amplification of keratin 19 mRNA with reverse transcriptase-polymerase chain reaction Noguchi,S.;Hiratsuka,M.;Furukawa,H. https://doi.org/10.1111/j.1349-7006.1996.tb00272.x
  12. Ann Thorac Surg v.61 Detection of disseminated lung cancer cells in lymph nodes: impact on staging and prognosis Passlick,B.;Izibicki,J.R.;Kubuschok(et al) https://doi.org/10.1016/0003-4975(95)01012-2
  13. Recent Rusults in Cancer Research v.157 Detection and relevance of immunohistochemically identifiable tumor cells in lymph nodes Passlick,B.;Pantel,K.
  14. J Thorac Cardiovasc Surg v.114 no.3 Metastatic p53-positive cells in the lymph nodes of non-small-cell lung cancer: prognostic significance Dobashi,K.;Sugio,K.;Osaki,T.;Oka,T.;Yasumoto,K. https://doi.org/10.1016/S0022-5223(97)70178-8
  15. J Natl Cancer Inst v.85 Frequency and distribution of occult micrometastasis in the lymph nodes of patients with non-small cell lung cancer Chen,Z.I.;Perez,S.;Holmes,C.E.(et al)
  16. J Thorac Cardiovasc Surg v.99 The significance of ipsilateral mediastinal lymph node metastasis( N2 disease) in non-small-cell cancer of the lung: a commentary Shields,T.W.
  17. J Thorac Cardiovasc Surg v.112 Mode of spread in the early phase of lymphatic metastasis in non-small cell lung cancer:significance of nodal micrometastasis Izbicki,J.R.;Passlick,B.;Kubuschock,B.(et al) https://doi.org/10.1016/S0022-5223(96)70044-2
  18. J Pathol v.172 The prognostic significance of immunohistochemically detected lymph node micrometastases in colorectal carcinoma Jeffers,M.D.;O'Dowd,G.M.;Mulcahy,H. (et al) https://doi.org/10.1002/path.1711720205
  19. Oncology v.57 Clinical implications of lymph node micrometastases in the patients with colorectal cancers. A case control study Nakanishi,Y.;Ochiai,A.;Yamauchi,Y.;Moriya,Y.;Yoshimura,K.;Hiroshi,S. https://doi.org/10.1159/000012060
  20. J Clin Onclol v.8 Epithelial tumor cells in bone marrow of patients with colorectal cancer: immunocytochemical detection, phenotypic characterization, and prognostic significance Schlimok,G.;Funke,I.;Bock,B.;Schweiberer,B.;Witte,J.;Reithmuller,G. https://doi.org/10.1200/JCO.1990.8.5.831
  21. Lancet v.1 The distribution of secondary growths in cancer of breast Paget,S.