Xiaoliang Zhao1, Justine N McCutcheon2, Bhaskar Kallakury2, Joeffrey J Chahine2, Drew Pratt3, Mark Raffeld3, Yulong Chen4, Changli Wang4, Giuseppe Giaccone5. 1. Department of Lung Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin Lung Cancer Center, Tianjin Key Laboratory of Cancer Prevention and Therapy, National Clinical Research Center for Cancer, Tianjin, People's Republic of China; Georgetown University, Washington, District of Columbia. 2. Georgetown University, Washington, District of Columbia. 3. Department of Pathology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland. 4. Department of Lung Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin Lung Cancer Center, Tianjin Key Laboratory of Cancer Prevention and Therapy, National Clinical Research Center for Cancer, Tianjin, People's Republic of China. 5. Georgetown University, Washington, District of Columbia. Electronic address: gg396@georgetown.edu.
Abstract
BACKGROUND: SCLC accounts for 15% and 20% of all lung cancers, with combined SCLC (CSCLC) comprising 2% to 5%. Little is known about the clinical characteristics and molecular changes associated with the various histologic components. METHODS: A total of 205 SCLC cases were resected between 2005 and 2015. Clinical and pathologic features were analyzed. All CSCLC cases were confirmed by histologic examination and immunohistochemistry. The individual components were microdissected using a novel automated dissection system, and DNA was extracted and subjected to targeted exome sequencing. RESULTS: A total of 10 cases of CSCLC were identified out of 170 cases with adequate histologic material; squamous cell carcinoma comprised the second component in half of these (n = 5). There were no significant differences between CSCLC and pure SCLC with respect to clinical features. The median follow-up time was 36 months. The median survival times of patients with pure SCLC and CSCLC were 58 months and 26 months, respectively (p = 0.030). The different components of three cases of CSCLC were deemed adequate for microdissection and sequencing. Approximately 75% of the identified somatic mutations were present in both components. There were also 15 gene mutations or six amplifications unique to only one of the components. CONCLUSIONS: We identified no significant clinical or pathologic differences between pure SCLC and CSCLC; CSCLC was associated with decreased overall survival compared with pure SCLC. The histologic components of CSCLC had high genetic concordance but also showed divergent genotypes. These findings may suggest a common precursor with subsequent acquisition of oncogenic changes in CSCLC.
BACKGROUND:SCLC accounts for 15% and 20% of all lung cancers, with combined SCLC (CSCLC) comprising 2% to 5%. Little is known about the clinical characteristics and molecular changes associated with the various histologic components. METHODS: A total of 205 SCLC cases were resected between 2005 and 2015. Clinical and pathologic features were analyzed. All CSCLC cases were confirmed by histologic examination and immunohistochemistry. The individual components were microdissected using a novel automated dissection system, and DNA was extracted and subjected to targeted exome sequencing. RESULTS: A total of 10 cases of CSCLC were identified out of 170 cases with adequate histologic material; squamous cell carcinoma comprised the second component in half of these (n = 5). There were no significant differences between CSCLC and pure SCLC with respect to clinical features. The median follow-up time was 36 months. The median survival times of patients with pure SCLC and CSCLC were 58 months and 26 months, respectively (p = 0.030). The different components of three cases of CSCLC were deemed adequate for microdissection and sequencing. Approximately 75% of the identified somatic mutations were present in both components. There were also 15 gene mutations or six amplifications unique to only one of the components. CONCLUSIONS: We identified no significant clinical or pathologic differences between pure SCLC and CSCLC; CSCLC was associated with decreased overall survival compared with pure SCLC. The histologic components of CSCLC had high genetic concordance but also showed divergent genotypes. These findings may suggest a common precursor with subsequent acquisition of oncogenic changes in CSCLC.
Authors: I I Wistuba; J Berry; C Behrens; A Maitra; N Shivapurkar; S Milchgrub; B Mackay; J D Minna; A F Gazdar Journal: Clin Cancer Res Date: 2000-07 Impact factor: 12.531
Authors: F R Hirsch; M J Matthews; S Aisner; O Campobasso; J D Elema; A F Gazdar; B Mackay; M Nasiell; Y Shimosato; R H Steele Journal: Cancer Date: 1988-09-01 Impact factor: 6.860
Authors: P A Radice; M J Matthews; D C Ihde; A F Gazdar; D N Carney; P A Bunn; M H Cohen; B E Fossieck; R W Makuch; J D Minna Journal: Cancer Date: 1982-12-15 Impact factor: 6.860
Authors: Franziska Böttger; Ekaterina A Semenova; Ji-Ying Song; Giustina Ferone; Jan van der Vliet; Miranda Cozijnsen; Rajith Bhaskaran; Lorenzo Bombardelli; Sander R Piersma; Thang V Pham; Connie R Jimenez; Anton Berns Journal: Cell Rep Date: 2019-06-11 Impact factor: 9.423