Prospective Cohort Study of Telomere Biology Among Patients With Early Adenocarcinoma of the Lung

Bronchoalveolar carcinoma has been traditionally used to refer to a subset of adenocarcinoma distinguished by its peripheral location, typical "lepidic" growth pattern and tendency for both bronchogenic and lymphatic spread. For the purpose of this discussion and consistency with the revised 2011 criteria, BAC subtypes will be collectively referred to as early adenocarcinoma.

The clinical presentation of early adenocarcinoma subtypes is highly variable ranging from a small solitary nodule to extensive lobar consolidation. Many peripheral lesions have a characteristic ground glass opacity appearance on Chest CT, which may correlate with an improved prognosis. The reported five-year disease-free survival after resection for isolated lesions may approaches 100%.

Preoperative diagnosis of such lesions is complicated by several limitations. First, the differential diagnosis is broad including an extensive number of inflammatory and infectious processes. Second, positron emission tomography (PET), which identifies regions of increased metabolic activity, may be falsely negative due to the slow growth of early adenocarcinoma lesions. Transbronchial needle biopsy is also unreliable to confirm or exclude disease in non-solid type lesions.

The proportion of lung cancers classified as adenocarcinoma has steadily increased and now comprises nearly ½ of cases. However, the proportion of adenocarcinoma in situ is uncertain. Previous reports range from 5-10% in a large series to as high as 24% in the large Surveillance, Epidemiology and End Results database. Thus, these early adenocarcinoma lesions may represent a disproportionately large number of lung cancers which are PET negative yet carry an excellent prognosis after early resection. The early adenocarcinoma subtypes represent a clinical entity requiring further characterization to distinguish lesions more likely to be malignant from benign.

Telomerase is activated aberrantly in most lung cancers and mutations in telomerase components predispose to solid malignancies. For patients with non-small cell lung cancer, numerous studies correlate increased tumor telomerase activity with increased likelihood of Stage IIIB and Stage IV disease and/or reduced survival. Furthermore, telomerase inhibition is currently being studied in clinical trials of patients with advanced non-small lung cancer.