MCM2 - a promising marker for premalignant lesions of the lung: a cohort study

BACKGROUND: Because cells progressing to cancer must proliferate, marker proteins specific to proliferating cells may permit detection of premalignant lesions. Here we compared the sensitivities of a classic proliferation marker, Ki-67, with a new proliferation marker, MCM2, in 41 bronchial biopsy specimens representing normal mucosa, metaplasia, dysplasia, and carcinoma in situ. METHODS: Parallel sections were stained with antibodies against MCM2 and Ki-67, and the frequencies of staining were independently measured by two investigators. Differences were evaluated statistically using the two-sided correlated samples t-test and Wilcoxon rank sum test. RESULTS: For each of the 41 specimens, the average frequency of staining by anti-MCM2 (39%) was significantly (p < 0.001) greater than by anti-Ki-67 (16%). In metaplastic lesions anti-MCM2 frequently detected cells near the epithelial surface, while anti-Ki-67 did not. CONCLUSIONS: We conclude that MCM2 is detectable in 2-3 times more proliferating premalignant lung cells than is Ki-67. The promise of MCM2 as a sensitive marker for premalignant lung cells is enhanced by the fact that it is present in cells at the surface of metaplastic lung lesions, which are more likely to be exfoliated into sputum. Future studies will determine if use of anti-MCM2 makes possible sufficiently early detection to significantly enhance lung cancer survival rates.