Gene Abberation Analysis in Precancerous Lesion of the Lung Adenocarcinoma by Laser Microdissection System

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Totally 65 AAH lesions(low/high grade atypia =45/20) were obtained from 13 of 21 (62%) cases surgically resected for peripheral type lung adenocarcinomas. The mean size of the AAH lesions was 1.7 mm in low grade AAH and 3.7 mm in high grade AAH (p<0.0001). All of the 4 AAH lesions over 5 mm in diameter showed high grade atypia. The means of the nuclear size and area were 7.22μm and 28.23μmィイD12ィエD1 in low grade AAH and 8.20μm and 36.01μmィイD12ィエD1 in high grade AAH(p=0.002 and p<0.0001, respectively). Nuclear size and nuclear area were also positively correlated with the AAH size(p<0.0001, in each). P53 and MIB-1 indexes also trend to increase from low grade AAH, to high grade AAH and to primary adenocarcinoma(p<0.0001, in each). These histopathological findings suggest that there is already a step-up in the atypia, lesion size, p53 and MIB-1 indexes from low grade to high grade AAH, and support the possibility that human AAH with high grade atypia is a precancerous lesion of peripheral lung adenocarcinoma. In addition, atypical cells in both low and high grade AAH lesions were immunohistochemically positive to SP-A and proSP-C(100%, in each), but negative to CC10(0%, in each), which indicates that the atypical cells of AAH lesions share the phenotypical characteristics of type II pneumocytes, and thus offers further support the hypothesis that AAH lesions largely may imply the proliferative lesion of type II pneumocytes of their derivative cells. In the gene abberation analysis, p53 gene abberation in exon 5 was noted in 4 of the 12 primary adenocarcinoma cases in which both AAH and primary adenocarcinoma could be aplied for p53 gene abberation analysis. One low grade AAH involved in one of the previous 4 casese revealed a same band shift with that of the primary adenocarcinoma.