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Published on: September 20, 2016
Comprehensive analysis of oncogenic mutations in lung squamous cell carcinoma with minor glandular component
Yunjian Pan1, Rui Wang1, Ting Ye1
1Department 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.
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.
Insights
Squamous cell carcinomas with minor glandular components (SQCC-mGCs) show a higher prevalence of oncogenic mutations in genes like EGFR and KRAS compared to pure squamous cell carcinomas (SQCCs). Identifying these mutations in SQCC-mGCs is crucial for guiding targeted therapy selection.
Area of Science:
- Oncology
- Genetics
- Pathology
Background:
- Oncogenic mutations in genes like EGFR, ALK, BRAF, HER2, DDR2, RET, and AKT1 identify non-small cell lung cancer (NSCLC) subsets responsive to targeted therapies.
- The mutational landscape, prevalence, and clinicopathologic features of squamous cell carcinomas with a minor glandular component (SQCC-mGCs) remain incompletely understood.
Purpose of the Study:
- To investigate the spectrum and prevalence of oncogenic mutations in lung squamous cell carcinoma (SQCC) subtypes.
- To compare the mutation rates between SQCCs with a minor glandular component (SQCC-mGCs) and pure SQCCs.
- To assess the clinical implications of these mutations for targeted therapy selection.
Main Methods:
- Histological reevaluation of 310 surgically resected SQCC specimens using hematoxylin-eosin and immunohistochemistry staining.
- Analysis of EGFR, KRAS, HER2, BRAF, PIK3CA, AKT1, and DDR2 mutations, alongside ALK and RET rearrangements, in 310 SQCCs via directed sequencing.
Main Results:
- Ninety-five SQCC-mGCs (30.6%) and 215 pure SQCCs (69.4%) were identified.
- Oncogenic mutations were detected in 27.4% of SQCC-mGCs (including EGFR, KRAS, PIK3CA, BRAF, HER2, and ALK alterations) versus 4.7% of pure SQCCs (including PIK3CA, AKT1, DDR2, and EGFR).
- KRAS mutations were exclusively found in SQCC-mGCs, and RET rearrangements were absent in all SQCCs.
Conclusions:
- SQCC-mGCs exhibit a significantly higher frequency of actionable oncogenic mutations (EGFR, ALK, KRAS) compared to pure SQCCs.
- Oncogenic mutations in EGFR, KRAS, BRAF, HER2, and ALK are rare in pure SQCCs.
- Prospective identification of these mutations in SQCC-mGCs is essential for optimizing targeted therapy selection and improving patient outcomes.
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