Suárez-Canto Julián, Suárez-Sánchez Faustino Julián, Domínguez-Iglesias Francisco, Hernández-Vallejo Gonzalo, García-Pedrero Juana M, de Vicente Juan C
395 Los Prados Cabueñes, 33394 Gijón, Asturias, Spain.
Department of Pathology, Hospital Universitario de Cabueñes, 395 Los Prados Cabueñes, 33394 Gijón, Asturias, Spain.
J Clin Med. 2018 Dec 10;7(12):534. doi: 10.3390/jcm7120534.
Zinc finger AN1-type containing 4 (ZFAND4) has emerged as a promising prognostic marker and predictor of metastasis for patients with oral squamous cell carcinoma (OSCC). However, further validation is fundamental before clinical implementation. Hence, this study evaluated the expression pattern of ZFAND4 protein expression by immunohistochemistry using an independent cohort of 125 patients with OSCC, and correlations with the clinicopathologic parameters and disease outcome. Remarkably, ZFAND4 expression, while negligible in normal epithelium, exhibited two distinct expression patterns in tumors that did not overlap. A gross granular staining was characteristic of the undifferentiated cells at the invasive front of tumors, whereas the most differentiated cells located at the center of the tumor nests showed diffuse non-granular staining. ZFAND4 staining was higher in undifferentiated than in differentiated areas of tumors. High ZFAND4 expression in differentiated cells was significantly associated to well-differentiated ( = 0.04) and non-recurrent tumors ( = 0.04), whereas ZFAND4 expression in undifferentiated cells correlated with tumor location ( = 0.005). No correlations between the ZFAND4 expression and patient survival were found. These data question the clinical relevance of ZFAND4 expression as a prognostic biomarker in OSCC, and also reveal distinct ZFAND4 expression patterns depending on the differentiation areas of tumors that should be evaluated separately.
含4个AN1型锌指蛋白（ZFAND4）已成为口腔鳞状细胞癌（OSCC）患者有前景的预后标志物和转移预测指标。然而，在临床应用前进一步验证至关重要。因此，本研究使用125例OSCC患者的独立队列，通过免疫组织化学评估ZFAND4蛋白表达的模式，以及与临床病理参数和疾病转归的相关性。值得注意的是，ZFAND4表达在正常上皮中可忽略不计，但在肿瘤中呈现两种不重叠的独特表达模式。粗大颗粒状染色是肿瘤侵袭前沿未分化细胞的特征，而位于肿瘤巢中心的分化程度最高的细胞显示弥漫性非颗粒状染色。肿瘤未分化区域的ZFAND4染色高于分化区域。分化细胞中高ZFAND4表达与高分化（P = 0.04）和无复发肿瘤（P = 0.04）显著相关，而未分化细胞中的ZFAND4表达与肿瘤位置相关（P = 0.005）。未发现ZFAND4表达与患者生存之间存在相关性。这些数据质疑了ZFAND4表达作为OSCC预后生物标志物的临床相关性，并且还揭示了取决于肿瘤分化区域的不同ZFAND4表达模式，应分别进行评估。
