Predicting malignant transformation of esophageal squamous cell lesions by combined biomarkers in an endoscopic screening program.
OBJECTIVE
To determine the association of p53, carcinoembryonic antigen (CEA) and CA19-9 protein expression with esophageal carcinogenesis.


METHODS
An iodine staining endoscopic screening program of esophageal lesions was carried out in the high-incidence area of Feicheng County, China. Seventy-seven patients with basal cell hyperplasia (BCH), 247 with low-grade dysplasia (LGD), 51 with high-grade dysplasia (HGD), 134 with invasive cancer, and 80 normal controls diagnosed by mucous membrane biopsy pathology were enrolled. Immunohistochemical detection of p53, CEA and CA19-9 proteins was performed. In the ROC curve analysis, the expression of a single biomarker and the expression of a combination of biomarkers were used to predict the risk of these four esophageal lesions.


RESULTS
The positive rates of p53 protein expression in invasive cancer, HGD, LGD, BCH and the normal control groups were 53.0%, 52.9%, 35.6%, 27.3% and 20.0%, respectively; the positive rates of CA19-9 protein expression were 44.0%, 33.3%, 16.5%, 9.2% and 6.2%, respectively; the positive rates of CEA protein expression were 74.6%, 60.8%, 23.3%, 23.7% and 16.2%, respectively. The positive rates of the combined expression of the three biomarkers were 84.3%, 76.5%, 47.6%, 42.9% and 27.5%, respectively. In the receiver operating characteristic curves of the combination of the three biomarkers, the specificity was 88.8% for the normal controls, and the sensitivity was 58.2% for invasive cancer, 25.5% for HGD, 11.2% for LGD, and 6.5% for BCH.


CONCLUSIONS
p53, CEA and CA19-9 protein expression was correlated with esophageal carcinogenesis, and testing for the combination of these biomarkers is useful for identifying high-risk patients with precancerous lesions.
Hao Zhang, Department of Gastroenterology, The Third Hospital of Jinan, Jinan 250132, Shandong Province, China.
Hao
H
Zhang
Hao Zhang, Department of Gastroenterology, The Third Hospital of Jinan, Jinan 250132, Shandong Province, China.
Hao
H
Li
Hao Zhang, Department of Gastroenterology, The Third Hospital of Jinan, Jinan 250132, Shandong Province, China.
Qing
Q
Ma
Hao Zhang, Department of Gastroenterology, The Third Hospital of Jinan, Jinan 250132, Shandong Province, China.
Fang-Yan
FY
Yang
Hao Zhang, Department of Gastroenterology, The Third Hospital of Jinan, Jinan 250132, Shandong Province, China.
Tao-Yu
TY
Diao
D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000378:metabolism*; D001706:Biopsy; D018395:CA-19-9 Antigen / Q000378:metabolism; D002272:Carcinoembryonic Antigen / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000000981:diagnostic imaging* / Q000378:metabolism*; D045744:Cell Line, Tumor; D002471:Cell Transformation, Neoplastic; D055088:Early Detection of Cancer; D004724:Endoscopy; D004938:Esophageal Neoplasms / Q000000981:diagnostic imaging* / Q000378:metabolism*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008403:Mass Screening / Q000379:methods; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D012372:ROC Curve; D011795:Surveys and Questionnaires; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
D014408:Biomarkers, Tumor; D018395:CA-19-9 Antigen; D002272:Carcinoembryonic Antigen; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53
CA19-9; Carcinoembryonic antigen; Esophageal squamous cell cancer; Esophageal squamous cell dysplasia; Immunohistochemistry; Prediction; p53