Sentinel lymph node mapping and molecular staging in nonsmall cell lung carcinoma

• Published in: Cancer 2005-10, Vol.104 (7), p.1453-1461
• Main Authors: Pulte, Dianne, Li, Eric, Crawford, Bernard K., Newman, Elliot, Alexander, Alice, Mustalish, David C., Jacobson, Daniel R.
• Format: Article
• Language: English
• Subjects: Aged; Base Sequence; Biological and medical sciences; Carcinoma, Non-Small-Cell Lung - mortality; Carcinoma, Non-Small-Cell Lung - pathology; Carcinoma, Non-Small-Cell Lung - surgery; Cohort Studies; cytokeratin 7; DNA, Neoplasm - analysis; Humans; Lung Neoplasms - mortality; Lung Neoplasms - pathology; Lung Neoplasms - surgery; Male; Medical sciences; Middle Aged; Molecular Biology; Molecular Sequence Data; molecular staging; Neoplasm Invasiveness - pathology; Neoplasm Staging - methods; nonsmall cell lung carcinoma; Pneumology; Pneumonectomy - methods; Predictive Value of Tests; Prognosis; Prospective Studies; Reverse Transcriptase Polymerase Chain Reaction - methods; Risk Assessment; Sensitivity and Specificity; sentinel lymph node; Sentinel Lymph Node Biopsy; Survival Analysis; Tumors; Tumors of the respiratory system and mediastinum
• ISSN: 0008-543X; 1097-0142
• DOI: 10.1002/cncr.21325

BACKGROUND Lymph node (LN) involvement predicts recurrence in patients who have undergone resection of apparently localized nonsmall cell lung carcinoma (NSCLC). Standard detection methods for LN disease have a low sensitivity, and many patients with apparent N0 disease status develop recurrent disease. Molecular techniques can improve the detection of micrometastases, whereas sentinel lymph node (SLN) mapping can indicate which LN may contain micrometastases. These methods, although potentially complementary, have not, to the authors' knowledge, been used together previously. METHODS The authors used SLN mapping and molecular staging to improve the detection of LN micrometastases in patients with NSCLC. Reverse transcriptase‐polymerase chain reaction (RT‐PCR) analysis for cytokeratin‐7 (CK7), expressed both in normal lung and in malignant lung, was used to identify tumor‐derived material in LN. RESULTS SLN mapping was performed in 13 patients, with 1–3 SLNs identified in each patient, and sufficient RNA for RT‐PCR was obtained in 12 of these 13 patients. Eleven of 12 tumors expressed CK7. Overall, 32 LNs were positive for CK7, including 13 of 21 SLNs. Ten of 11 patients with evaluable SLNs had at least 1 CK7‐positive SLN. Routine pathology showed Stage I disease in eight patients, T3N0 disease in one patient, and LN‐positive disease in two patients. Of the nine patients with N0 disease according to routine pathology that was evaluable by RT‐PCR, eight patients were upstaged by this technique. All patients with positive LN status by routine pathology who were evaluable by RT‐PCR analysis had positive RT‐PCR results. CONCLUSIONS LN micrometastases were common in resected NSCLC, including patients with N0 disease according to routine pathology. SLN mapping was useful for identifying disease‐containing LNs. This approach may be useful for stratifying histologically N0 patients into higher risk and lower risk groups. Cancer 2005. Published 2005 by the American Cancer Society. Thirteen patients who underwent surgery for lung carcinoma with curative intent also underwent sentinel lymph node (SLN) mapping and molecular staging by reverse transcriptase‐polymerase chain reaction analysis, techniques that had not been employed together previously in any malignancy. This approach improved the sensitivity of detecting lymph node micrometastases: Several patients with N0 disease, as determined with routine pathology and immunohistochemistry, were upstaged to molecular