Diagnostic and prognostic significance of squamous cell carcinoma antigen in non-small cell lung cancer

doi:10.1016/S0169-5002(00)00225-7

Lung Cancer

Volume 32, Issue 2, May 2001, Pages 137-144

https://doi.org/10.1016/S0169-5002(00)00225-7 Get rights and content

Abstract

Squamous cell carcinoma antigen (SCC-Ag) is a glycoprotein secreted by non-small cell lung tumours (NSCLC). This study investigated the diagnostic and prognostic significance of SCC-Ag in NSCLC. Receiver operating characteristic (ROC) curve analysis was used to test the diagnostic performance of the SCC-Ag and determine the optimal threshold value in a group of 100 NSCLC patients undergoing surgery and 50 age matched healthy controls. This threshold was then prospectively validated in a group of 53 patients and 49 healthy controls. The prognostic significance of the preoperative SCC-Ag level and its postoperative decrease were tested using univariate and multivariate proportional hazard models. The area under the ROC curve was 0.71±0.04, and the best cutoff value was 1.4 ng/ml. This discriminated patients in the validation group, with a sensitivity of 0.55 and a specificity of 1.0. The hazard ratio was 0.144 (95% CI 0.074–0.281) for the postoperative decrease in the SCC Ag, and 5.823 (3.299–10.278) for the preoperative SCC Ag level. Multivariate analysis revealed that only disease stage and patients’ age are strong prognostic factors for survival. In conclusion, the SCC-Ag serum level has moderate diagnostic role in NSCLC. Both the preoperative SCC-Ag level and its postoperative decrease have prognostic significance, yet inferior to the disease stage and the patient's age.

Introduction

Squamous cell carcinoma (SCC) antigen, a subfraction of the TA-4 antigen, is a glycoprotein secreted by various tumours, including those of the lung [8]. Studies conducted to investigate the usefulness of the SCC antigen in the diagnosis and prognosis of lung cancer, have produced contradictory results [1], [2], [3], [5], [7], [8], [9], [10], [11]. Most of these studies have used arbitrarily defined cut-off values of the SCC antigen serum level to discriminate lung cancer patients from control subjects, which might have adversely affected the performance of this tumour marker. Furthermore, the results obtained from these studies were not prospectively validated [6].

To circumvent this problem we have used receiver operator characteristic (ROC) curve analysis to test the diagnostic performance of the SCC antigen and determine the optimal threshold value in a group of non-small cell lung cancer (NSCLC) patients undergoing curative surgery and age matched controls (derivation group). This threshold value was afterwards prospectively validated in another group of NSCLC patients and controls (validation group) [6].

The prognostic significance of preoperative SCC antigen level in lung cancer patients is rather limited [2], [10]. Nevertheless, the SCC antigen level decreases after surgery. The prognostic significance of this decrease in SCC antigen level after surgery has not been adequately tested. We, therefore, also studied the prognostic significance of the decrease in SCC antigen level after surgery, and compared it with other predictors of survival of NSCLC patients.

Section snippets

Materials and methods

We have measured SCC antigen in the serum of 153 patients with primary NSCLC (149 males, 62±10 years old), before and 1 month after surgery, and in 99 age matched healthy controls (97 males), using a commercially available ELISA kit (Abbot Laboratories, USA). Patients (77) had SCC, 45 had adenocarcinoma (ADC) and 31 patients had large cell carcinoma (LCC). The inclusion period was from May 1994 to August 1996.

Patients had been considered as candidates for surgery based on clinical and

Results

The preoperative serum SCC-Ag level of the lung cancer patients was 1.4 ng/ml (0.9–2.9 ng/ml) in the derivation group (median, 25–75% percentiles) and 1.5 ng/ml (0.9–2.4 ng/ml) in the validation group, whereas the respective values of the healthy controls were 1 (0.6–1.3 ng/ml) and 0.8 ng/ml (0.6–1 ng/ml) (P<0.05). As expected, the serum SCC-Ag level decreased postoperatively to 0.65 (0.3–1 ng/ml) and 0.6 ng/ml (0.4–1 ng/ml) in the derivation and validation groups, respectively (P<0.05).

Discussion

The major findings of this study are, (1) SCC Ag serum level has moderate diagnostic role in NSCLC; (2) both the preoperative SCC-Ag serum level and its postoperative decrease have prognostic significance, yet inferior to the one provided by the disease stage and the patient's age.

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A new magneto-controlled microfluidic device for direct electrochemical determination of squamous cell carcinoma antigen (SCC-Ag) in serum was designed by using anti-SCC antibody (SCC-Ab)-functionalized magnetic mesoporous nanogold/thionine/NiCo₂O₄ hybrid nanostructures as immunosensing probes (P₁-Ab) and horseradish peroxidase-SCC-Ab conjugates-labeled nanogold/graphene nanosheets as signal tags (P₂-Ab). In the presence of the analyte SCC-Ag, the sandwich immunocomplex was formed between the immunosensing probes and the signal tags. With the aid of an external magnet, the formed immunocomplex was attached to the microfluidic device. The assay was implemented in newborn calf serum (NBCS) containing 2.5 mM H₂O₂ based on the labeled peroxidase on the P₂-Ab toward the catalytic reduction of H₂O₂. Under optimal conditions, the increase in the current was proportional to the concentration of SCC-Ag from 2.5 pg/mL to 15 ng/mL. The detection limit (LOD) was 1.0 pg/mL SCC-Ag at 3s_B. The electrochemical immunoassay displayed an acceptable precision, selectivity and stability. Clinical serum specimens were assayed with the method, and the results were in acceptable agreement with those obtained from the referenced electrochemiluminescent method. Importantly, the method can be suitable for on-line use in the mass production of miniaturized lab-on-a-chip devices and open a new opportunity for protein diagnostics and biosecurity.
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Diagnostic and prognostic significance of squamous cell carcinoma antigen in non-small cell lung cancer

Abstract

Introduction

Section snippets

Materials and methods

Results

Discussion

Chest

Squamous cell carcinoma antigen as an adjunct tumour marker in primary carcinoma of the lung

J. Clin. Pathol.

Prediction of survival and recurrence by serum and cytosolic levels of CEA, CA125 and SCC antigens in resectable non-small-cell lung cancer

Br. J. Cancer.

Diagnostic validity of the SCC antigen assays in squamous cell carcinoma of the lung

J. Tumour Marker Oncol.

The meaning and use of the area under a receiver operating characteristic (ROC) curve

Radiology

Clinical prediction rules. A review and suggested modifications on methodological standards

J. Am. Med. Assoc.