+ Site Statistics
+ Search Articles
+ PDF Full Text Service
How our service works
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ Translate
+ Recently Requested

Comprehensive analysis of oncogenic mutations in lung squamous cell carcinoma with minor glandular component

Comprehensive analysis of oncogenic mutations in lung squamous cell carcinoma with minor glandular component

Chest 145(3): 473-479

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. 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. 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. 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.

Please choose payment method:

(PDF emailed within 0-6 h: $19.90)

Accession: 052269843

Download citation: RISBibTeXText

PMID: 24158231

DOI: 10.1378/chest.12-2679

Related references

Comprehensive investigation of clinicopathologic features, oncogenic driver mutations and immunohistochemical markers in peripheral lung squamous cell carcinoma. Journal of Thoracic Disease 9(11): 4434-4440, 2017

Comprehensive profiling and quantitation of oncogenic mutations in non-small cell lung carcinoma using single-molecule amplification and re-sequencing technology. Tumour Biology 39(2): 1010428317691413-1010428317691413, 2017

Comprehensive profiling and quantitation of oncogenic mutations in non small-cell lung carcinoma using single molecule amplification and re-sequencing technology. Oncotarget 7(31): 50477-50489, 2016

Metastatic Squamous Cell Carcinoma Component from an Adenosquamous Carcinoma of the Lung with Identical Epidermal Growth Factor Receptor Mutations. Case Reports in Pulmonology 2015: 283875-283875, 2015

Rapid onset lung squamous cell carcinoma with prominent peritoneal carcinomatosis and an eosinophilic leukemoid reaction, with coexistence of the BRAF V600E and oncogenic KRAS G12A mutations: A case report. Oncology Letters 8(2): 589-593, 2014

MA 13.02 Comprehensive Genetic Analysis Related to PD-L1 Expression in Early-stage Lung Squamous Cell Carcinoma. Journal of Thoracic Oncology 12(11): S1851-S1852, 2017

Analysis of Fifty Hotspot Mutations of Lung Squamous Cell Carcinoma in Never-smokers. Journal of Korean Medical Science 32(3): 415-420, 2017

Comprehensive investigation of oncogenic driver mutations in Chinese non-small cell lung cancer patients. Oncotarget 6(33): 34300-8, 2016

Analysis of HYAL3 gene mutations in Chinese lung squamous cell carcinoma patients. Tumori 99(1): 108-112, 2013

Common oncogenic mutations are infrequent in oral squamous cell carcinoma of Asian origin. Plos One 8(11): E80229-E80229, 2014

Do oncogenic drivers exist in squamous cell carcinoma of the lung?. Oncology 27(9): 906, 913-4, 2013

Small cell anaplastic carcinoma of the lung with glandular and squamous differentiation. American Journal of Surgical Pathology 5(3): 307-309, 1981

Late occurrence of K-ras gene mutations in the pathogenesis of squamous cell carcinoma of the lung: analysis in sputum. Analytical and Quantitative Cytology and Histology 18(6): 501-502, 1996

Lung Cancer with a Small Cell Carcinoma Component Diagnosed from Pleural Effusion and a Squamous Cell Carcinoma Component Diagnosed from the Tumor. Internal Medicine 57(23): 3419-3422, 2018

Afatinib against Esophageal or Head-and-Neck Squamous Cell Carcinoma: Significance of Activating Oncogenic HER4 Mutations in HNSCC. Molecular Cancer Therapeutics 15(8): 1988-1997, 2017