Paired analysis of tumor mutation burden for lung adenocarcinoma and associated idiopathic pulmonary fibrosis.

Genetic alterations underlying the development of lung cancer in individuals with idiopathic pulmonary fibrosis (IPF) have remained unclear. To explore whether genetic alterations in IPF tissue contribute to the development of IPF-associated lung cancer, we here evaluated tumor mutation burden (TMB) and somatic variants in 14 paired IPF and tumor samples from patients with IPF-associated lung adenocarcinoma. We also determined TMB for 22 samples of lung adenocarcinoma from patients without IPF. TMB for IPF-associated lung adenocarcinoma was significantly higher than that for matched IPF tissue (median of 2.94 vs. 1.26 mutations/Mb, P = 0.002). Three and 102 somatic variants were detected in IPF and matched lung adenocarcinoma samples, respectively, with only one pair of specimens sharing one somatic variant. TMB for IPF-associated lung adenocarcinoma was similar to that for lung adenocarcinoma samples with driver mutations (median of 2.94 vs. 2.51 mutations/Mb) and lower than that for lung adenocarcinoma samples without known driver mutations (median of 2.94 vs. 5.03 mutations/Mb, P = 0.130) from patients without IPF. Our findings suggest that not only the accumulation of somatic mutations but other factors such as inflammation and oxidative stress might contribute to the development and progression of lung cancer in patients with IPF.

Operative results of clinical stage I non-small cell lung cancer.

BACKGROUND: Clinical stage (c-stage) I non-small cell lung cancer (NSCLC) is generally indicated for surgery, however, surgical exploration sometimes reveals advanced disease, thus resulting in incomplete resection. PATIENTS AND METHODS: A total of 645 consecutive patients were investigated in which 347 were diagnosed to have c-stage IA in 347 and 298 were diagnosed to have IB disease. All cases underwent operation and were investigated for resectability and the cause of an incomplete resection. RESULTS: The c-Stage IA patients included 16.6% of T3/4 and 10.4% of N2 whereas clinical stage IB patients included 14.4% of T3/4 and 18.8% of N2/3. A complete resection was performed in 594 patients (91%). In 347 c-stage IA patients, the complete resection rates were 93% in adenocarcinomas (235/252), 100% in squamous cell carcinomas (76/76), and 89% in others (17/19). In 298 c-stage IB patients, the complete resection rates were 86% in adenocarcinomas (141/164), 90% in squamous cell carcinomas (90/100), and 94% in others (31/33). The 5-year survival rates of the c-stage IA and IB patients who underwent a complete resection were 66.4 and 48.3%, respectively. However, the same rates were 18.4 and 14.7% for c-stage IA and IB patients who underwent an incomplete resection. The reasons for an incomplete resection in 54 patients were malignant pleurisy in 38 (70.4%), extranodal invasion of mediastinal nodal metastasis in ten (19%), an incomplete bronchial margin in three (5.6%), and ipsilateral pulmonary metastases in two (3.7%), and ipsilateral adrenal metastasis in one (1.3%). In 13% of the c-stage IB adenocarcinomas, pleural metastasis was discovered during thoracotomy. CONCLUSIONS: Pleural dissemination was the most frequent cause of an incomplete resection, and its prevalence was high in c-stage IB adenocarcinomas.