Wang Xiao-Nan, Wang Shu-Jing, Pandey Vijay, Chen Ping, Li Qing, Wu Zheng-Sheng, Wu Qiang, Lobie Peter E
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.
Medicine (Baltimore). 2015 May;94(20):e860. doi: 10.1097/MD.0000000000000860.
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.
在癌症中，如肺癌，组织学亚型对于为患者选择合适的治疗策略很重要。然而，低分化癌仅根据形态学或临床发现往往无法区分。因此，区分低分化腺癌和鳞状细胞癌这两种最常见的上皮源性癌，对于选择最佳治疗方法至关重要。在此，我们探讨了三叶因子3（TFF3）作为原发性肺腺癌及源自不同器官的肺外腺癌生物标志物的潜在效用。我们观察到90.9%的肺腺癌TFF3呈阳性，而鳞状细胞癌未观察到TFF3表达。肺癌的亚型通过四种既定的生物标志物得以确认，细胞角蛋白7和甲状腺转录因子1用于腺癌，P63和细胞角蛋白5/6用于鳞状细胞癌。此外，通过定量PCR在11个人类肺腺癌细胞系中均观察到TFF3 mRNA的表达，且与腺癌谱系标志物高度相关。相比之下，在4个肺鳞状细胞癌细胞系中未观察到或仅观察到少量TFF3表达。通过强制表达或siRNA介导的TFF3缺失，我们确定TFF3似乎维持而非促进肺癌细胞的腺分化。此外，还检测了来自结肠、胃、宫颈、食管和喉的腺癌中的TFF3表达。在所有这些肺外癌中，93.7%的腺癌TFF3呈阳性，而鳞状细胞癌仅有2.9%为TFF3阳性。总体而言，肺和肺外腺癌中92.9%的TFF3呈阳性，而鳞状细胞癌仅有1.5%为TFF3阳性。总之，TFF3在腺癌中优先表达，可作为区分腺癌与鳞状细胞癌的额外生物标志物。
