Yunjian Pan1, Rui Wang1, Ting Ye1, Chenguang Li1, Haichuan Hu2, Yongfu Yu3, Yang Zhang2, Lei Wang1, Xiaoyang Luo1, Hang Li4, Yuan Li5, Lei Shen5, Yihua Sun6, Haiquan Chen7. 1. Department of Thoracic Surgery, Fudan University Shanghai Cancer Center, the Department of Biostatistics, School of Public Health, Fudan University, Shanghai, China; Department of Oncology, the Department of Biostatistics, School of Public Health, Fudan University, Shanghai, China. 2. Department of Oncology, the Department of Biostatistics, School of Public Health, Fudan University, Shanghai, China. 3. Shanghai Medical College, and the Department of Biostatistics, School of Public Health, Fudan University, Shanghai, China. 4. Department of Thoracic Surgery, Fudan University Shanghai Cancer Center, the Department of Biostatistics, School of Public Health, Fudan University, Shanghai, China; Department of Pathology, Fudan University Shanghai Cancer Center, the Department of Biostatistics, School of Public Health, Fudan University, Shanghai, China. 5. Department of Thoracic Surgery, Fudan University Shanghai Cancer Center, the Department of Biostatistics, School of Public Health, Fudan University, Shanghai, China; Department of Pathology, Fudan University Shanghai Cancer Center, the Department of Biostatistics, School of Public Health, Fudan University, Shanghai, China; Department of Oncology, the Department of Biostatistics, School of Public Health, Fudan University, Shanghai, China. 6. Department of Oncology, the Department of Biostatistics, School of Public Health, Fudan University, Shanghai, China; Department of Thoracic Surgery, Fudan University Shanghai Cancer Center, the Department of Biostatistics, School of Public Health, Fudan University, Shanghai, China. 7. Department of Oncology, the Department of Biostatistics, School of Public Health, Fudan University, Shanghai, China; Department of Thoracic Surgery, Fudan University Shanghai Cancer Center, the Department of Biostatistics, School of Public Health, Fudan University, Shanghai, China. Electronic address: hqchen1@yahoo.com.
Abstract
BACKGROUND: The mutations in oncogenic genes, such as EGFR, ALK, BRAF, HER2, DDR2, RET, and AKT1, defined subsets of non-small cell lung cancers (NSCLCs) with potential sensitivity to targeted therapies. At present, the mutational spectrum, prevalence, and clinicopathologic characteristics in squamous cell carcinomas with minor (<10%) glandular component (SQCC-mGCs) are not well established. METHODS: Three hundred ten surgically resected lung squamous cell carcinoma (SQCC) specimens were collected. The histology of all cases was reevaluated using hematoxylin-eosin and immunohistochemistry staining. EGFR, KRAS, HER2, BRAF, PIK3CA, AKT1, and DDR2 mutations, as well as ALK and RET rearrangements, were examined in 310 SQCCs by directed sequencing. RESULTS: Ninety-five SQCC-mGCs (30.6%) and 215 pure SQCCs (69.4%) were identified. Of the 95 SQCC-mGCs, 26 (27.4%; 95% CI, 18.7%-37.4%) were found to harbor known oncogenic mutations, including 10 with EGFR, seven with KRAS, three with PIK3CA, one with BRAF, one with HER2, one each with EGFR/PIK3CA and KRAS/PIK3CA double mutations, and two with EML4-ALK fusions. Ten of 215 pure SQCCs (4.7%; 95% CI, 2.3%-8.4%) harbored mutations, including seven with PIK3CA, and each with AKT1, DDR2, and EGFR. No RET rearrangements were detected in SQCCs. SQCC-mGCs had a significantly higher rate of mutations in known oncogenic genes than that in pure SQCCs (27.4% vs 4.7%, P<.001). All KRAS mutations occurred in SQCC-mGCs. CONCLUSIONS: Our results demonstrated that oncogenic mutations in EGFR, KRAS, BRAF, HER2, and ALK were extremely rare or absent in patients with pure SQCC, whereas SQCC-mGC had a relatively high frequency of EGFR, ALK, or KRAS mutations. Prospective identification of these known oncogenic mutations in SQCC-mGC before the initiation of treatment is an essential step to identify which patient could benefit from targeted therapies.
BACKGROUND: The mutations in oncogenic genes, such as EGFR, ALK, BRAF, HER2, DDR2, RET, and AKT1, defined subsets of non-small cell lung cancers (NSCLCs) with potential sensitivity to targeted therapies. At present, the mutational spectrum, prevalence, and clinicopathologic characteristics in squamous cell carcinomas with minor (<10%) glandular component (SQCC-mGCs) are not well established. METHODS: Three hundred ten surgically resected lung squamous cell carcinoma (SQCC) specimens were collected. The histology of all cases was reevaluated using hematoxylin-eosin and immunohistochemistry staining. EGFR, KRAS, HER2, BRAF, PIK3CA, AKT1, and DDR2 mutations, as well as ALK and RET rearrangements, were examined in 310 SQCCs by directed sequencing. RESULTS: Ninety-five SQCC-mGCs (30.6%) and 215 pure SQCCs (69.4%) were identified. Of the 95 SQCC-mGCs, 26 (27.4%; 95% CI, 18.7%-37.4%) were found to harbor known oncogenic mutations, including 10 with EGFR, seven with KRAS, three with PIK3CA, one with BRAF, one with HER2, one each with EGFR/PIK3CA and KRAS/PIK3CA double mutations, and two with EML4-ALK fusions. Ten of 215 pure SQCCs (4.7%; 95% CI, 2.3%-8.4%) harbored mutations, including seven with PIK3CA, and each with AKT1, DDR2, and EGFR. No RET rearrangements were detected in SQCCs. SQCC-mGCs had a significantly higher rate of mutations in known oncogenic genes than that in pure SQCCs (27.4% vs 4.7%, P<.001). All KRAS mutations occurred in SQCC-mGCs. CONCLUSIONS: Our results demonstrated that oncogenic mutations in EGFR, KRAS, BRAF, HER2, and ALK were extremely rare or absent in patients with pure SQCC, whereas SQCC-mGC had a relatively high frequency of EGFR, ALK, or KRAS mutations. Prospective identification of these known oncogenic mutations in SQCC-mGC before the initiation of treatment is an essential step to identify which patient could benefit from targeted therapies.
Authors: Christine M Lusk; Donovan Watza; Greg Dyson; Douglas Craig; Valerie Ratliff; Angela S Wenzlaff; Fulvio Lonardo; Aliccia Bollig-Fischer; Gerold Bepler; Kristen Purrington; Shirish Gadgeel; Ann G Schwartz Journal: Clin Cancer Res Date: 2019-04-12 Impact factor: 12.531