title: Trefoil factor 3 as a novel biomarker to distinguish between adenocarcinoma and squamous cell carcinoma.
abstract: In carcinoma, such as of the lung, the histological subtype is important to select an appropriate therapeutic strategy for patients. However, carcinomas with poor differentiation cannot always be distinguished on the basis of morphology alone nor on clinical findings. Hence, delineation of poorly differentiated adenocarcinoma and squamous cell carcinoma, the 2 most common epithelial-origin carcinomas, is pivotal for selection of optimum therapy. Herein, we explored the potential utility of trefoil factor 3 (TFF3) as a biomarker for primary lung adenocarcinoma and extrapulmonary adenocarcinomas derived from different organs. We observed that 90.9% of lung adenocarcinomas were TFF3-positive, whereas no expression of TFF3 was observed in squamous cell carcinomas. The subtype of lung carcinoma was confirmed by four established biomarkers, cytokeratin 7 and thyroid transcription factor 1 for adenocarcinoma and P63 and cytokeratin 5/6 for squamous cell carcinoma. Furthermore, expression of TFF3 mRNA was observed by quantitative PCR in all of 11 human lung adenocarcinoma cell lines and highly correlated with markers of the adenocarcinomatous lineage. In contrast, little or no expression of TFF3 was observed in 4 lung squamous cell carcinoma cell lines. By use of forced expression, or siRNA-mediated depletion of TFF3, we determined that TFF3 appeared to maintain rather than promote glandular differentiation of lung carcinoma cells. In addition, TFF3 expression was also determined in adenocarcinomas from colorectum, stomach, cervix, esophagus, and larynx. Among all these extrapulmonary carcinomas, 93.7% of adenocarcinomas exhibited TFF3 positivity, whereas only 2.9% of squamous cell carcinomas were TFF3-positive. Totally, 92.9% of both pulmonary and extrapulmonary adenocarcinomas exhibited TFF3 positivity, whereas only 1.5% of squamous cell carcinomas were TFF3-positive. In conclusion, TFF3 is preferentially expressed in adenocarcinoma and may function as an additional biomarker for distinguishing adenocarcinoma from squamous cell carcinoma.
authors.affiliation: From the Department of Pathology (X-NW, S-JW, PC, QL, Z-SW, QW); Laboratory of Pathogenic Microbiology and Immunology, Anhui Medical University, Hefei, Anhui, People's Republic of China (X-NW); Cancer Science Institute of Singapore and Department of Pharmacology, National University of Singapore (VP, PEL); and National Cancer Institute of Singapore, National University Health System, Singapore (PEL). These authors contributed equally to this work.
authors.forename: Xiao-Nan
authors.initials: XN
authors.lastname: Wang
authors.forename: Shu-Jing
authors.initials: SJ
authors.lastname: Wang
authors.forename: Vijay
authors.initials: V
authors.lastname: Pandey
authors.forename: Ping
authors.initials: P
authors.lastname: Chen
authors.forename: Qing
authors.initials: Q
authors.lastname: Li
authors.forename: Zheng-Sheng
authors.initials: ZS
authors.lastname: Wu
authors.forename: Qiang
authors.initials: Q
authors.lastname: Wu
authors.forename: Peter E
authors.initials: PE
authors.lastname: Lobie
mesh_terms: D000230:Adenocarcinoma / Q000737:chemistry* / Q000175:diagnosis; D015415:Biomarkers / Q000032:analysis; D002294:Carcinoma, Squamous Cell / Q000737:chemistry* / Q000175:diagnosis; D045744:Cell Line, Tumor; D006801:Humans; D053552:Keratin-7 / Q000032:analysis; D008175:Lung Neoplasms / Q000737:chemistry / Q000175:diagnosis; D009369:Neoplasms / Q000737:chemistry; D009687:Nuclear Proteins / Q000032:analysis; D010455:Peptides / Q000032:analysis*; D016133:Polymerase Chain Reaction; D000074482:Thyroid Nuclear Factor 1; D014157:Transcription Factors / Q000032:analysis; D000071165:Trefoil Factor-3
chemical_list: D015415:Biomarkers; D053552:Keratin-7; C000614412:NKX2-1 protein, human; D009687:Nuclear Proteins; D010455:Peptides; C082495:TFF3 protein, human; D000074482:Thyroid Nuclear Factor 1; D014157:Transcription Factors; D000071165:Trefoil Factor-3