Article Abstract

Microsatellite alteration in plasma DNA discriminates multiple primary lung cancer from metastatic lung cancer

Authors: Long Tian, Xin Wang, Rujun Zeng, Cheng Shen, Yutian Lai, Kun Zhou, Guowei Che


Background: To develop a novel molecular approach as a noninvasive test for differentiation of tumor origin, and to evaluate the feasibility of distinguishing multiple primary lung cancer (MPLC) from metastatic lung cancer (MLC) through the analysis of microsatellite genomic instability of plasma DNA.
Methods: Matched normal, tumor, and plasma samples were obtained from 12 patients with single lesions. After DNA extraction, the samples were subjected to microsatellite analysis using 6 markers (D2S1363, D6S1056, D7S1824, D10S1239, D15S822, and D22S689). Tumor and plasma samples were collected from 12 patients with multiple lesions. Of them, 6 patients were diagnosed as multiple primary tumors and 6 patients as pulmonary metastasis according to the last version of guideline proposed by American College of Chest Physicians.
Results: In the single lesion group, 33 (45.8%) of 72 plasma tests displayed positive polymerase chain reaction (PCR)-results. Of the 43 tumor samples with positive PCR-results, 31 (72.1%) could also be detected in plasma. In the multiple lesion group, 8 and 4 patients showed the “contradictory trend” and the “unique trend”, respectively in the plasma analysis. However, in the tumor analysis, 10 and 2 patients showed the “contradictory trend” and the “unique trend”, respectively. The sensitivity and specificity of plasma tests to identify multiple primary tumors are 80% (8/10) and 100% (2/2), respectively.
Conclusions: Identical microsatellite alteration could be observed in both circulating DNA and the tumor. With polymorphic microsatellite markers, the “contradictory trend” representing multiple primary tumors that is detected in tumor cells and plasma DNA could assist in discriminating MPLC and MLC.