Serum Carcinoembryonic Antigen Levels before Initial Treatment are Associated with EGFR Mutations and EML4-ALK Fusion Gene in Lung Adenocarcinoma Patients

Wang, Wentao; Li, Yin; Ma, Jie; Chen, Xiaobing; Qin, Jianjun

doi:10.7314/apjcp.2014.15.9.3927

Cited by 13 publications

(11 citation statements)

References 33 publications

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“…These results were consistent with previous studies in NSCLC (10,15,18). CEA is an important serum tumor marker; recent studies have found that patients with ALK rearrangement were seen more frequently to have normal serum CEA level in lung adenocarcinoma (19,20). However the study populations of these retrospective investigations were most with early clinical stage.…”

Section: Discussionsupporting

confidence: 92%

Comparison of clinical and radiological characteristics between anaplastic lymphoma kinase rearrangement and epidermal growth factor receptor mutation in treatment naïve advanced lung adenocarcinoma

Miao

Zhu

et al. 2017

J. Thorac. Dis.

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Background: Gene analysis could not be performed in all patients, especially in advanced non-small cell lung cancer (NSCLC). We aimed to find some clinical futures and CT or FDG-PET characteristics, which could be combined to help distinguish anaplastic lymphoma kinase (ALK) rearrangement form epidermal growth factor receptor (EGFR) mutations in treatment naïve advanced lung adenocarcinoma of Chinese patients. Methods:We retrospectively reviewed clinical and radiological characteristics of 145 patients with treatment naïve advanced lung adenocarcinoma. The one-way ANOVA, the Mann-Whitney test, chi-square test and logistic regression were used for comparison between patients with ALK rearrangement and those with EGFR mutation.Results: Among 145 patients with advanced lung adenocarcinoma, only six patients had both ALK rearrangement and EGFR mutation, the sample size was too small to analysis. Univariate analysis revealed that patients with ALK rearrangement were younger (P=0.001) and with lower serum carcinoembryonic antigen (CEA) level (P=0.008) than those with EGFR mutation. More of tumors with ALK rearrangement were well defined (P=0.023) and have bubble lucency (P=0.026) compared with those with EGFR mutation (P=0.026). Lymphadenopathy was seen more frequently in patients with ALK rearrangement (P=0.167). Twenty-six patients received FDG-PET/CT, among this population, lesion standardized uptake values (SUV)>6.95 and lymph nodes SUV max >6.25 were more often seen in ALK rearrangement group (P=0.011, both).In multivariate analysis, patients younger than 50 years (RR =9.878, 95% CI: 2.318-42.090, P=0.002), with lower CEA level than 4.95 μg/L (RR =8.166, 95% CI: 1.085-31.983, P=0.003) and without brain metastasis (RR =7.304, 95% CI: 1.099-48.558, P=0.040) were more likely to be ALK rearrangement than EGFR mutation. Tumor diameter less than 36 mm were prone to be EGFR mutation (RR =0.078, 95% CI: 0.017-0.356, P=0.001).Conclusions: Treatment naïve advanced lung adenocarcinomas with ALK rearrangement were more likely to have younger age, lower serum CEA level, larger tumor volume, well defined tumor border, and non-brain metastasis than those with EGFR mutation. Bubble lucency and higher FDG uptake of lesion and lymph nodes may help distinguish ALK rearrangement from EGFR mutation in the absence of genetic analysis.

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Section: Discussionsupporting

confidence: 92%

Comparison of clinical and radiological characteristics between anaplastic lymphoma kinase rearrangement and epidermal growth factor receptor mutation in treatment naïve advanced lung adenocarcinoma

Miao

Zhu

et al. 2017

J. Thorac. Dis.

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“… 13 – 15 Some believe that this discrepancy is because patients with higher CEA levels are more likely to have a positive EGFR mutation. 14 , 18 After removing EGFR mutation status as a confounding factor, our study revealed that higher baseline CEA was associated with worse outcomes in EGFR -mutant patients treated with EGFR-TKIs, which was in line with study focus on colorectal cancer treated with bevacizumab-based therapies. 32 …”

Section: Discussionsupporting

confidence: 79%

“… 13 – 15 This phenomena may be attributed to a higher EGFR mutation rate in patients with higher CEA levels. 14 , 18 However, previous studies also revealed that higher CEA level was correlated with higher tumor burden and more advanced stage. 19 …”

Section: Introductionmentioning

confidence: 99%

Baseline, Trend, and Normalization of Carcinoembryonic Antigen as Prognostic Factors in Epidermal Growth Factor Receptor-Mutant Nonsmall Cell Lung Cancer Patients Treated With First-Line Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors

et al. 2015

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Among epidermal growth factor receptor (EGFR) mutation status unknown nonsmall cell lung cancer (NSCLC) patients, those with higher carcinoembryonic antigen (CEA) level are more likely to response to EGFR-tyrosine kinase inhibitors (TKIs) because they tend to have mutant epidermal growth factor receptor (EGFR). However, patients with higher CEA also have more tumor burden. With the above paradoxical evidence, it is prudent to understand the prognostic significance of baseline CEA in patients with EGFR-mutant NSCLC treated with first-line EGFR-TKIs. The clinical significance of the trend in CEA after treatment and the impact of CEA normalization during EGFR-TKI therapy are also unknown and potentially important.A total of 241 patients who received first-line EGFR-TKIs were included. As to baseline CEA, patients were divided into normal, low, and high baseline CEA by cut point determined by receiver operating characteristic curves. As to CEA responses, patients were divided into 3 groups accordingly to their amount of CEA change after taking TKIs. In group A, 1-month follow-up CEA level decreased more than 35% with nadir CEA normalization; in group B, 1-month follow-up CEA level decreased more than 35% without nadir CEA normalization; and in group C, 1-month follow-up CEA level decreased less than 35% or increased.Patients with higher baseline CEA levels had shorter progression-free survival (PFS) and overall survival (OS) (CEA > 32 vs 5–32 vs <5 ng/mL, PFS = 8.8 vs 11.3 vs 14.4 months, respectively, P < 0.001; OS = 17.8 vs 22.0 vs 27.9 months, respectively, P = 0.01). For trend and CEA normalization in groups A, B, and C, PFS was 14.3, 10.6, and 7.1 months, respectively (P < 0.001); OS was 29.7, 20.0, and 16.2 months, respectively (P < 0.001).Baseline, trend, and normalization of CEA levels are potential prognostic markers for patients with EGFR-mutant advanced NSCLC treated with first line EGFR-TKIs.

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“…In NSCLC, serum CEA levels have been widely reported as being correlated with advanced disease, EGFR mutation, and survival. [13][14][15] Our study marks the first time serum CEA levels were compared among lung adenocarcinoma histologic subtypes; differences were detected using the Kruskal-Wallis test (P = 0.004). We suspect that the LPA subtype with lower CEA levels might indicate better survival than the APA subtype with higher CEA levels.…”

Section: Discussionmentioning

confidence: 99%

Identification of lung adenocarcinoma mutation status based on histologic subtype: Retrospective analysis of 269 patients

Dong

et al. 2015

Thoracic Cancer

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BackgroundTo evaluate differences in the clinical characteristics and molecular pathology of lung adenocarcinoma subtypes as defined by the new International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society international histological classification.MethodsWe retrospectively reviewed 269 patients with initial primary lung adenocarcinoma who had undergone complete resection at our department from August 2013 to December 2014, focusing on the new histologic subtype classification, clinical characteristics, and molecular pathology.ResultsAll specimens were invasive adenocarcinoma, and were lepidic (13.0%), papillary (19.7%), acinar (51.7%), solid (8.6%), micropapillary (1.1%) or mucinous predominant (5.9%). Epidermal growth factor receptor (EGFR) mutations were detected in 132 cases (60.3%). Female patients and non‐smokers had higher EGFR mutation rates (P = 0.022 and 0.026, respectively). The lepidic, papillary, acinar, solid, micropapillary, and mucinous predominant patterns had EGFR mutation rates of 70.6%, 64.8%, 72.5%, 33.3%, 100%, and 5.9%, respectively. The exon mutation distribution differed according to serum carcinoembryonic antigen (CEA) levels (P = 0.018). v‐Ki‐ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS) mutations were detected in 20 cases (9.2%), and were frequently found in the mucinous and solid predominant subtypes. The serum CEA levels differed among the subtypes.ConclusionsIn China, there are significant differences between lung adenocarcinoma histologic subtypes. The presence of well‐differentiated components in lung adenocarcinoma indicates higher EGFR mutation rates; the presence of solid or mucinous components indicates higher KRAS mutation rates. Serum CEA levels are associated with histologic subtype and EGFR exon mutations.

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Serum Carcinoembryonic Antigen Levels before Initial Treatment are Associated with EGFR Mutations and EML4-ALK Fusion Gene in Lung Adenocarcinoma Patients

Cited by 13 publications

References 33 publications

Comparison of clinical and radiological characteristics between anaplastic lymphoma kinase rearrangement and epidermal growth factor receptor mutation in treatment naïve advanced lung adenocarcinoma

Comparison of clinical and radiological characteristics between anaplastic lymphoma kinase rearrangement and epidermal growth factor receptor mutation in treatment naïve advanced lung adenocarcinoma

Baseline, Trend, and Normalization of Carcinoembryonic Antigen as Prognostic Factors in Epidermal Growth Factor Receptor-Mutant Nonsmall Cell Lung Cancer Patients Treated With First-Line Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors

Identification of lung adenocarcinoma mutation status based on histologic subtype: Retrospective analysis of 269 patients

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