It has been suggested that atypical adenomatous hyperplasia (AAH) may be a precursor of peripheral adenocarcinoma of the lung. Telomerase is a ribonucleoprotein enzyme that synthesizes telomeric DNA onto chromosomal ends. Its activity is believed to be crucial for cellular immortality, and it is thought to participate in the development of most human cancers. However, little is known about the regulation of telomerase in AAH. We investigated the expression of human telomerase RNA component (hTERC) and telomerase reverse transcriptase (hTERT) mRNA using in situ hybridization in surgically resected formalin-fixed, paraffin-embedded specimens: 29 AAHs (with 11 lesions interpreted as low-grade AAH and 18 as high-grade AAH) and 40 peripherally located nonmucinous bronchioloalveolar carcinomas (NMBACs) measuring < or = 20 mm in greatest diameter. Positive expressions of hTERC and hTERT mRNA were recognized in 27.3% and 27.3% of low-grade AAHs, 72.2% and 77.8% of high-grade AAHs, and 97.5% and 97.5% of NMBACs, respectively. Statistically, significant differences in both expressions could be shown between low-grade AAH and high-grade AAH and between high-grade AAH and NMBAC. Thus, in terms of the incidence of these expressions, high-grade AAH was intermediate between low-grade AAH and NMBAC and tended to be closer to NMBAC. These results suggest that high-grade AAH may be a precursor lesion of peripherally located NMBAC.
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