Abstract
Defining distinctive histologic characteristics of ROS1-rearranged non-small-cell lung carcinomas (NSCLCs) may help identify cases that merit molecular testing. However, the majority of previous reports have focused on surgical specimens but only limited studies assessed histomorphology of advanced NSCLCs. In order to identify the clinical and histological characteristics of ROS1-rearranged advanced NSCLCs, we examined five hundred sixteen Chinese patients with advanced NSCLCs using ROS1 fluorescence in situ hybridization and real-time polymerase chain reaction and then analyzed for clinical and pathological features. We performed univariate and multivariate analyses to identify predictive factors associated with ROS1 rearrangement. 19 tumors were identified with ROS1 rearrangement (3.7% of adenocarcinomas). 16 ROS1+ and 122 ROS1- samples with available medical records and enough tumor cells were included for histological analysis. Compared with ROS1-negative advanced NSCLCs, ROS1-rearranged advanced NSCLCs were associated with a younger age at presentation. ROS1 rearrangements were not significantly associated with sex, smoking history, drinking history and metastatic sites. The most common histological pattern was solid growth (12/16), followed by acinar (4/16) growth. 66.7% cases with solid growth pattern showed hepatoid cytology (8/12) and 75% cases with acinar growth pattern showed a cribriform structure (3/4). 18.8% cases were found to have abundant extracellular mucus or signet-ring cells (3/16). Only one case with solid growth pattern showed psammomatous calcifications. In conclusion, age, hepatoid cytology and cribriform structure are the independent predictors for ROS1-rearranged advanced NSCLCs, recognizing these may be helpful in finding candidates for genomic alterations, especially when available tissue samples are limited.
Highlights
Lung carcinomas are the leading cause of cancerrelated mortality worldwide [1]
Age, hepatoid cytology and cribriform structure are the independent predictors for ROS1-rearranged advanced non-small-cell lung carcinomas (NSCLCs), recognizing these may be helpful in finding candidates for genomic alterations, especially when available tissue samples are limited
Of the 516 consecutive patients from the advanced NSCLCs, ROS1 rearrangements were detected in 19 cases (3.7%) using real-time PCR, 488 cases were negative and 9 cases failed
Summary
Lung carcinomas are the leading cause of cancerrelated mortality worldwide [1]. Adenocarcinoma is the most common histologic type of lung cancer [2]. The ROS1-rearranged non-small-cell lung carcinomas (NSCLCs) have been reported to be sensitive to the kinase inhibitor crizotinib [7]. Boland et al found that 26% pulmonary adenocarcinoma with signet ring cell features were ALK rearrangement [8]. Approximately 70% of patients are at advanced stage when diagnosed For these patients, the small biopsies or cytological specimens are the only limited pathologic material available for diagnosis and molecular testing. The small biopsies or cytological specimens are the only limited pathologic material available for diagnosis and molecular testing It is still unclear whether the findings from prior studies are applicable to specimens from metastatic lung tumors, small biopsies or cytology specimens
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