Investigation of micrometastasis by cytokeratin staining in non-small cell lung cancer patients with tumor negative mediastinoscopic lymph node biopsies

Yıl 2013, Cilt: 30 Sayı: 2, 119 - 124, 31.07.2013

Sinan Kaya Ahmet Başoğlu Yasemin Büyükkarabacak Burçin  Çelik Ayşen Şengül Tülin Yetim Levent Yıldız

https://doi.org/10.5835/jecm.omu.30.02.006

Öz

To investigate micrometastasis by using epithelial cytokerati marker in non-small cell lung cancer (NSCLC) patients with tumor negative mediastinoscopic lymph node biopsies. Micrometastasis were investigated by immunohistochemical staining in 20 patients who were diagnosed as NSCLC with ipsilateral mediastinal lymph nodes (RN2) in CT scan and with negative histopathologic mediastinoscopic lymph node biopsy (pN0). Frozen section was studied with hematoxylin-eosin (HE), a routine histopatological method in lymph nodes taken by mediastinoscopy and in absence of metastasis; resection was applied with thoracotomy in the same session. We studied micrometastasis in lymph nodes, which are taken out by mediastinoscopy and dissected during resection, using both HE and immunohistochemical staining with cytokeratin. All patients were male and median age was 60.9 (51-74) years. In 16 cases epidermoid carcinoma, in 2 cases adenocarcinoma and in 2 cases bronchioloalveoler carcinoma were diagnosed as histopathological types. Cervical mediastinoscopy was performed in 20 patients who were diagnosed as RN2 by thorax CT radiologically, and complete resection was done in pN0 patients. Sixty lymph nodes, 40 of them taken by mediastinoscopy and 20 taken during resection, were stained immunohistochemically in 20 NSCLC patients. Only one lymph node from a single patient was positive after staining. After postoperative staging, 18 patients were at a lower stage, one patient was at the same stage, and one patient with micro metastasis was at an advanced stage. Immunohistochemical staining may be useful in detecting micrometastasis in NSCLC. Standard cervical mediastinoscopy is still gold standard in preoperative staging. Efficiency can be increased by combining mediastinoscopy, a gold standard method in staging, with immunohistochemical methods.

Anahtar Kelimeler

Cytokeratin, Immunohistochemical staining, Lung cancer, Mediastinoscopy, Micrometastasis

Kaynakça

• Baron, R.L., Levitt, R.G., Sagel, S.S., White, M.J., Roper, C.L., Marbarger, J.P., 1982. Computed tomography in the preoperative evaluation of bronchogenic carcinoma. Radiology. 145, 727-732.
• Brion, J.P., Depauw, L., Kuhn, G., de Fracquen, P., Friberg, J., Rocmans, P., Struyven, J., 1985. Role of computed tomography and mediastinoscopy in preoperative staging of lung carcinoma. J. Comput. Assist. Tomogr. 9, 480-484.
• Chen, Z.L., Perez, S., Holmes, E.C., Wang, H.J., Coulson, W.F., Wen, D.R., Cochran, A.J., 1993. Frequency and distribution of occult micrometastases in lymph nodes of patients with non-small-cell lung carcinoma. J. Natl. Cancer. Inst. 85, 493-498.
• Gonzalez-Stawinski, G.V., Lemaire, A., Merchant, F., O’Halloran, E., Coleman, R.E., Harpole, D.H., D’Amico, T.A., 2003. A comparative analysis of positron emission tomography and mediastinoscopy in staging non-small cell lung cancer. J. Thorac. Cardiovasc. Surg. 126, 1900-1905.
• Gu, C.D., Osaki, T., Oyama, T., Inoue, M., Kodate, M., Dobashi, K. Oka, T., Yasumuto, K., 2002. Detection of micrometastatic tumor cells in pN0 lymph nodes of patients with completely resected nonsmall cell lung cancer: Impact on recurrence and survival. Ann. Surg. 235, 133- 139.
• Gurses, A., Turna, A., Bedirhan, M.A., Ozalp, T., Kocaturk, C., Demir, A., Ozcan, M., Urer N, 2002. The value of mediastinoscopy in preoperative evaluation of mediastinal involvement in non-small-cell lung cancer patients with clinical N0 disease. Thorac. Cardiovasc. Surg. 50, 174-177.
• International Breast Cancer Study Group, 1990. Prognostic significance of occult axillary lymph node micrometastases from breast cancers. Lancet. 335, 1565-1568.
• Izbicki, J.R., Passlick, B., Hosch, S.B., Kubuschock, B., Schneider, C., Busch, C., Knoefel, W.T., Thetter, O., Pantel, K., 1996. Mode of spread in the early phase of lymphatic metastasis in non-small-cell lung cancer: Significance of nodal micrometastasis. J. Thorac. Cardiovasc. Surg. 112, 623-630.
• Kernstine, K.H., Mclaughlin, K.A., Menda, Y., Rossi, N.P., Kahn, D.J., Bushnell, D.L., Graham, M.M, Brown, C.K., Madsen, M.T., 2002. Can FDG-PET reduce the need mediastinoscopy in potentially resectable nonsmall cell lung cancer? Ann. Thorac. Surg. 73, 394-402.
• Kramer, H., Groen, H.J., 2003. Current concepts in the mediastinal lymph node staging of nonsmall cell lung cancer. Ann. Surg. 238, 180-188.
• Lowe, V.J., Fletcher, J.W., Gobar, L., Lawson, M., Kirchner, P., Valk, P., Karis, J., Hubner, K., Delbeke, D., Heiberg, E.V., Patz, E.F., Coleman, R.E., 1998. Prospective investigation of positron emission tomography in lung nodules. J. Clin. Oncol. 16, 1075-1084.
• Luke, W.P., Pearson, F.G., Todd, T.R., Patterson, G.A., Cooper, J.D., 1986. Prospective evaluation of mediastinoscopy for assessment of carcinoma of the lung. J. Thorac. Cardiovasc. Surg. 91, 53-56.
• Martini, N., Bains, M.S., Burt, M.E., Zakowski, M.F., McCormack, P., Rusch, V.W., Ginsberg, R.J., 1995. Incidence of local recurrence and second primary tumors in resected stage I lung cancer. J. Thorac. Cardiovasc. Surg. 109, 120-129.
• Maruyama, R., Sugio, K., Mitsudomi, T., Saitoh, G., Ishida, T., Sugimachi, K., 1997. Relationship between early recurrence and micrometastases in the lymph nodes of patients with stage I non-small-cell lung cancer. J. Thorac. Cardiovasc. Surg. 114, 535-543.
• Mountain, C.F. 1997. Revisions in the International System for Staging Lung Cancer. Chest. 111, 1710-1717.
• Nishio, M., Koshikawa, T., Kuroishi, T., Suyama, M., Uchida, K., Takagi, Y., Washimi, O., Sugiura, T., Ariyoshi, Y., Takahashi, T., Ueda, R., Takahashi, T., 1996. Prognostic significance of abnormal p53 accumulation in primary, resected non-small-cell lung cancers. J. Clin. Oncol. 14, 497-502.
• Osaki, T., Oyama, T., Gu, C.D., Yamashita, T., So, T., Takenoyama, M., Sugio, K., Yasumoto, K., 2002. Prognostic impact of micrometastatic tumor cells in the lymph nodes and bone marrow of patients with completely resected stage I non-small-cell lung cancer. J. Clin. Oncol. 20, 2930-2936.
• Passlick, B., Pantel, K., 1996. Prognostic factors in stage I non-small cell bronchial carcinoma. Zentralbl. Chir. 121, 851-870.
• Passlick, B., Izbicki, J.R., Kubuschok, B., Thetter, O., Pantel, K., 1996. Detection of disseminated lung cancer cells in lymph nodes: Impact on staging and prognosis. Ann. Thorac. Surg. 61, 177-183.
• Schimmer, C., Neukam, K., Elert, O., 2006. Staging of non-small cell lung cancer: Clinical value of positron emission tomography and mediastinoscopy. Interact. Cardiovasc. Thorac. Surg. 5, 418-423.
• Sugio, K., Ishida, T., Yokoyama, H., Inoue, T., Sugimachi, K., Sasazuki, T., 1992. Ras gene mutations as a prognostic marker in adenocarcinoma of the human lung without lymph node metastasis. Cancer. Res. 52, 2093-2096.
• Toloza, E.M., Harpole, L., McCrory, D.C., 2003. Noninvasive staging of non-small cell lung cancer: A review of the current evidence. Chest. 123, 137-146.
• Toloza, E.M., Harpole, L., Detterbeck, F., McCrory, D.C., 2003. Invasive staging of non-small cell lung cancer: A review of the current evidence. Chest. 123, 157-166.
• Traweek, S.T., Liu, J., Battifora, H., 1993. Keratin gene expression in non-epithelial tissues. Detection with polymerase chain reaction. A.M. J. Pathol. 142, 1111-1118.
• Yasumoto, K., Osaki, T., Watanabe, Y., Kato, H., Yoshimura, T., 2003. Prognostic value of cytokeratin-positive cells in the bone marrow and lymph nodes of patients with resected nonsmall cell lung cancer: a multicenter prospective study. Ann. Thorac. Surg. 76, 194-202.