Effect of histologic type and smoking status on interpretation of serum carcinoembryonic antigen value in non–small cell lung carcinoma

doi:10.1016/j.athoracsur.2004.03.019

The Annals of Thoracic Surgery

Volume 78, Issue 3, September 2004, Pages 1004-1009

https://doi.org/10.1016/j.athoracsur.2004.03.019 Get rights and content

Abstract

Background

Serum carcinoembryonic antigen (CEA) has all of the properties desired for a biologic measure to be used as a prognostic indicator in the clinical evaluation of lung cancer. Carcinoembryonic antigen value appears to be related to tumor histologic type and patients' smoking status, which has yet to be intensively analyzed as reports available thus far have consisted of a limited number of patients. This study was undertaken to determine whether the prognostic value of CEA differs according to histologic type in a large group of patients with clinical early-stage lung cancer, and how smoking influences its value.

Methods

Two series of 694 and 260 consecutive patients who underwent resection for clinical stage I lung adenocarcinoma and squamous cell carcinoma, respectively, were evaluated. We measured serum CEA before and after surgery, and analyzed its prognostic significance in relation to histologic type and its correlation with smoking status.

Results

We found significantly higher CEA levels in patients with adenocarcinomas than in those with squamous cell carcinomas (7.8 versus 5.5 ng/mL; p = 0.0018), but a higher percentage of CEA-positive patients among those with squamous cell carcinoma (109 of 260, 41.9%) than those with adenocarcinoma (245 of 694, 35.3%). Clinical stage I patients with a high preoperative CEA level had a poor prognosis, and for pathologically confirmed stage I patients with a high postoperative CEA level the prognosis was worse. The prognostic value of serum CEA level was thus significantly greater for adenocarcinoma than for squamous cell carcinoma. This was probably because of a much higher proportion of smokers among patients with squamous cell carcinoma. In adenocarcinoma, the growth of which was generally less influenced by smoking, the proportion of CEA-positive smokers (49.3%, 170 of 345) was greater than that of CEA-positive nonsmokers (21.5%, 75 of 349, p < 0.0001). Additionally, in patients with adenocarcinoma, survival of nonsmokers was more greatly influenced by CEA level than that of smokers.

Conclusions

Although serum CEA values measured before and after surgery are important in identifying patients at high risk of poor survival, its specificity is higher for adenocarcinoma than for squamous cell carcinoma. When serum CEA levels are checked, smoking status of patients, particularly of those with squamous cell carcinoma, should be taken into account.

Section snippets

Material and methods

From January 1985 through December 2002, two series of 694 and 260 consecutive patients with clinical stage I disease were operated on for proven primary adenocarcinoma and squamous cell carcinoma of the lung, respectively. The histologic type of tumor was determined by applying the World Health Organization classification. In all patients, we measured serum CEA before and after surgery and resected the primary tumor. The tumor was measured directly in the surgical specimens. For preoperative

Results

Clinical characteristics, surgical treatment, and pathologic stage are summarized in Table 1. Compared with squamous cell carcinoma patients, adenocarcinoma patients were younger (p < 0.0001), included a higher number of women (p < 0.0001), had a smaller tumor (p < 0.0001), and had higher levels of preoperative serum CEA (p = 0.0018). However, the percentage of preoperative CEA-positive patients was higher in the squamous cell carcinoma group (41.9% versus 35.3%). The two groups were fairly

Comment

Preoperative serum CEA value had independent prognostic value after adjusting for sex, age, tumor size, and histologic type as evaluated in patients treated surgically for clinical stage I non–small cell lung cancer. Its increase was related to clinically and statistically significant reduction in survival even after intentional curative resection for early-stage disease. Although serum CEA value does not appear to be a specific marker of lung cancer, it is an essential prognostic factor. Thus,

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Besides cancer CEA expression is affected by other factor like non-malignant diseases (chronic bronchitis, emphysema,colits) (Rule et al., 1972; Fujishima et al., 1995). CEA is reported both LUSC (41.9%) and LUAD (35.3%) (Okada et al., 2004). However, we observed no significant difference in CEA transcripts expression, histopathologically between LUSC and LUAD; between non-smokers with poor AQI and moderate AQI (Fig. 4) as well as between chronic smokers (under Poor/Moderate AQI) and non-smokers with poor AQI (Fig. 4).
Smoking tobacco is the major hazard for lung cancer in Indian subcontinent especially men, compare to woman where, other important risk factors such as air pollutions are responsible. So, the aim of the study is to compare chronic smokers (CS) and non-smokers living in areas with air quality categorized as poor (AQI 201–300) or moderate (AQI 101–200). We measured the expression of non-small cell lung cancer (NSCLC) biomarkers;. IDH1, CEA, Cyfra21-1, and TPA through quantitative Real-Time PCR (qRT-PCR) and compared the levels of upregulation of the transcripts in stage IIIa NSCLC over control benign tissues among the smoking and AQI settings. Though the all biomarkers were significantly up-regulated in tumor tissues compared to control benign tissues, the fold change increase of IDH1 and CEA was highest in CS-poor/moderate AQI, followed by non-smokers-poor AQI and non-smokers moderate AQI. This indicates the aggressiveness and poor prognosis in CS living in either poor or moderate AQI areas. The level of Cyfra21-1 was lower in in the CS groups in comparison to non-smokers in the poor AQI area. This suggest higher Lung Squamous cell carcinoma histology in non-smokers living areas with poor AQI. Hence, we conclude that poor air quality can be as injurious for lung cancers as chronic smoking.
The predictive and prognostic significance of liquid biopsy in advanced epidermal growth factor receptor-mutated non-small cell lung cancer: A prospective study
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Therefore it is only found at very low levels in the blood of healthy adults [23]. However, levels can be elevated in heavy smokers [24]. The use of CEA as a prognostic and predictive marker for NSCLC is widely debated with studies showing contradictory results [11].
To determine the predictive and prognostic roles of three blood-based biomarkers: circulating tumour DNA (ctDNA), circulating tumour cells (CTC) and carcinoembryonic antigen (CEA), in patients with advanced epidermal growth factor receptor-mutated (EGFR+) lung cancer.
We recruited 28 patients with 103 serial blood samples. We performed mutational analyses for EGFR mutations using droplet digital PCR (ddPCR) on ctDNA. We evaluated the accuracy of EGFR mutation detection in ctDNA compared with tissue biopsy. We also quantified CTCs, ctDNA and CEA in serially collected blood samples, and evaluated the baseline and changes in these blood-based biomarkers with clinical outcomes.
EGFR mutation detection in plasma was highly concordant as compared with tissue biopsy. Detectable baseline ctDNA was associated with higher disease burden (p < 0.01). Early disappearance of ctDNA at 4 weeks was associated with radiological response at 12 weeks of treatment (p = 0.01) and improved progression free survival (PFS) (HR 5.47, 95%CI 1.32–22.72, p = 0.02) and overall survival (OS) (HR 5.46, 95%CI 1.28–23.22, p = 0.02). A decrease in CTC count at 4 weeks was associated with improved PFS (HR 3.81, 95%CI 1.13–12.79, p = 0.03) but not OS. 85% of patients with radiological progression had a ctDNA rise compared with 22% of patients with stable disease (p=0.01). ctDNA rise was seen on average 170 days prior to radiological progression. There is a significant association between the rise of CEA level with radiological progression (p=0.001).
Early change in ctDNA, CTC and CEA levels may be long-term predictors of treatment benefit and failure prior to availability of radiological response data.
Associations between serum carcinoembryonic antigen levels and adenocarcinoma subtypes of the lung
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Increased serum carcinoembryonic antigen (CEA) levels have been associated with a poor outcome in lung cancer. The aim of this study was to further clarify the associations between CEA levels and adenocarcinoma subtypes.
We retrospectively assessed preoperative serum CEA levels and clinicopathological factors in 307 consecutive patients who underwent resection for primary lung adenocarcinoma with curative intent.
Subtypes included adenocarcinoma in situ (AIS) in 20 cases, minimally invasive adenocarcinoma (MIA) in 20, invasive mucinous adenocarcinoma (IMA) in three, lepidic predominant adenocarcinoma (LPA) in 41, papillary predominant adenocarcinoma (PPA) in 106, acinar predominant adenocarcinoma (APA) in 90, solid predominant adenocarcinoma (SPA) in 23, and micropapillary predominant adenocarcinoma (MPA) in four. Serum CEA levels varied according to gender, age, smoking status, clinical stage, lymph node metastasis, pathological stage, and adenocarcinoma subtype. Serum CEA levels were higher in the APA, MPA, IMA, and SA subtypes than in the AIS, MIA, PPA, and LPA subtypes. Multiple regression analysis revealed that the clinical stage and adenocarcinoma subtype were significantly associated with serum CEA levels. Univariate analysis demonstrated that preoperative CEA levels were significantly associated with both the postoperative disease-free survival (DFS) and overall survival. Cox regression analysis revealed that the clinical stage and adenocarcinoma subtype were significantly associated with the postoperative DFS.
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Some unfavorable prognostic factors for stage I non–small-cell lung cancers have been reported; however, they are not reflected in the current Tumor–Node–Metastasis classification.
We retrospectively reviewed 629 patients who underwent complete resection of pathological stage I adenocarcinomas (ADs) or squamous cell carcinomas (SQs) at two institutes between 1996 and 2011. The correlation between clinicopathological characteristics and survival rates was analyzed to identify prognostic factors.
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Original article: general thoracicEffect of histologic type and smoking status on interpretation of serum carcinoembryonic antigen value in non–small cell lung carcinoma

Abstract

Background

Methods

Results

Conclusions

Section snippets

Material and methods

Results

Comment

Lancet

Chest

Pretreatment evaluation of non–small-cell lung cancer

Am J Respir Crit Care Med

Prognostic value of preoperative carcinoembryonic antigen (CEA) plasma levels in patients with bronchogenic carcinoma

Cancer

Carcinoembryonic antigen and prognosis after radical surgery for lung cancerimmunocytochemical localization and serum levels

Br J Cancer

Measurement of carcinoembryonic antigen in patients with bronchogenic carcinoma

Cancer

Original article: general thoracic
Effect of histologic type and smoking status on interpretation of serum carcinoembryonic antigen value in non–small cell lung carcinoma