The Impact of Immunohistochemical Detection of Positive Lymph Nodes in Early Stage Lung Cancer

Abstract

Background: Detection of micrometastatic disease is an interesting area in non-small cell lung cancer (NSCLC). We conducted a study to determine whether the detection of mediastinal lymph node spread by immunohistochemical (IHC) analysis offers some prognosis with respect to patients' disease-free survival or not. Methods: Between 1997 and 2003, twenty-one early stage lung cancer patients underwent complete resection with mediastinoscopy and systemic nodal dissection. Four hundred and twenty-six paraffin-embedded lymph node sections from 21 patients were analyzed. Epithelial specific-antigen Ab-9 and Keratin-Pan Ab-1 were used as IHC marker. Results: Based on nodal spread four of the 21 patients (19.04 %) were up-staged after IHC analysis. Two patients with stage IB (T2N0) up-staged to stage IIIA (T2N2); two patients staged as IIB (T2N1) up-staged to IIIA (T2N2). Statistical analysis showed that the lymphatic dissemination detected with IHC analysis was associated with reduced disease-free survival (DFS) (p = 0.002). Conclusions: Our study provides some indication that patients with lymphatic micrometastasis have a reduced DFS. Before creating a new TNM staging system, more information is needed to understand the prognostic impact of micrometastatic dissemination.

Key words

Lung cancer - diagnosis and staging - lymph nodes - immunohistochemistry

References

• 1 Sanson M. Fait remarkable de diathèse cancereuse. Gaz med de Paris 1834; 2: 140. Cited by Papac R. Bone marrow metastases.  Cancer. 1994;  74 2403-2413
• 2 Ryall C. The technique of cancer operations, with reference to the danger of cancer infection.  BMJ. 1908;  2 1005-1008
• 3 Gusterson B, Ott R. Occult axillary lymph-node micrometastases in breast cancer [letter].  Lancet. 1990;  336 434-435
• 4 Hermanek P, Hutter R, Sobin L, Wittekind C. Classification of isolated tumor cells and micrometastasis.  Cancer. 1999;  86 2668-2673
• 5 ATS/ERS guide.  Am J Respir Crit Care Med. 1997;  156 320
• 6 Sobin L H, Wittekind (eds) C M. International Union Against Cancer (UICC): TNM Classification of Malignant Tumors. 5th ed. New York; John Wiley 1997: 91-97
• 7 Singletary S E, Allread C, Ashley P, Bassett L W, Berry D, Bland K I, Borgen P. et al . Revision of the American Joint Committee on cancer staging system for breast cancer.  J Clin Oncol. 2002;  20 3628-3636
• 8 Passlick B, Izbicki J, Kubuschok B, Thetter O, Pantel K. Detection of disseminated lung cancer cells in lymph nodes: Impact on staging and prognosis.  Ann Thorac Surg. 1996;  61 177-183
• 9 Ahrendt S, Yang S, Wu L, Roig C, Russell P, Westra W. et al . Molecular assessment of lymph nodes in patients with resected stage I non-small cell lung cancer: Preliminary results of a prospective study.  J Thorac Cardiovasc Surg. 2002;  123 466-474
• 10 Feinstein A, Sosin D, Wells C. The Will Rogers phenomenon.  N Engl J Med. 1985;  312 1604
• 11 Sienel W, Hibler R S, Mutschler W, Pantel K, Passlick B. Tumour cells in the draining vein of patients with non-small cell lung cancer: detection rate and clinical significance.  Eur J Cardiothorac Surg. 2003;  23 451-455
• 12 Izbicki J, Passlick B, Hosch S B, Kubuschock B, Schneider C, Busch C. et al . Mode of spread in the early phase of lymphatic metastasis in non-small cell lung cancer: Significance of nodal micrometastasis.  J Thorac Cardiovasc Surg. 1996;  112 623-627
• 13 Ohta Y, Nozawa H, Oda M, Watanabe Y. Increased vascular endothelial growth factor and vascular endothelial growth factor-c and decreased NM23 expression associated with microdissemination in the lymph nodes in stage I non-small cell lung cancer.  J Thorac Cardiovasc Surg. 2000;  119 804-813
• 14 Nicholson A G, Graham A NJ, Pezzella F, Angeta G, Goldstraw P, Pastorino U. Does the use of immunohistochemistry to identify micrometastases provide useful information in the staging of node negative non-small cell lung cancer?.  Lung Cancer. 1997;  18 231-240
• 15 Keller S, Adak S, Wagner H, Johnson D. Mediastinal lymph node dissection improves survival in patients with stages II and IIIa non-small cell lung cancer.  Ann Thorac Surg. 2000;  70 358-366
• 16 Funke I, Schoraut W. Meta-analyses of studies on bone marrow micrometastases: An independent prognostic impact remains to be substantiated.  J Clin Oncol. 1998;  16 557-566