Kamikawa Yoshiaki, Kanmura Yuji, Hamada Tomofumi, Yamada Norishige, Macha Muzafar A, Batra Surinder K, Higashi Michiyo, Yonezawa Suguru, Sugihara Kazumasa
Department of Oral Surgery, Kagoshima University Hospital, 8-35-1 Sakuragaoka, Kagoshima, 890-8544, Japan.
Int J Clin Oncol. 2015 Apr;20(2):298-307. doi: 10.1007/s10147-014-0710-6. Epub 2014 Jun 10.
Both MUC1 and MUC4 are high molecular weight glycoproteins and are independent indicators of worse prognosis in many human epithelial cancers including oral squamous cell carcinoma (OSCC). However, there has been no investigation of the clinical importance of the co-expression of MUC1 and MUC4 in OSCC. The aim of this study was to evaluate the co-expression profile of MUC1/MUC4 and analyze the prognostic significance in OSCC.
We examined the expression profile of MUC1 and MUC4 in OSCC tissues from 206 patients using immunohistochemistry. The co-expression profile of MUC1/MUC4 and its prognostic significance in OSCC was statistically analyzed.
MUC1 and MUC4 overexpression were strongly correlated with each other (p < 0.0001) and a combination of both MUC1 and MUC4 expression was a powerful indicator for tumor aggressiveness such as tumor size (p = 0.014), lymph node metastasis (0.0001), tumor stage (p = 0.006), diffuse invasion (p = 0.028), and vascular invasion (p = 0.014). The MUC1/MUC4 double-positive patients showed the poorest overall and disease-free survival. Multivariate analysis revealed that MUC1/MUC4 double-positivity was the strong independent prognostic factor for overall and disease-free survival (p = 0.007 and (p = 0.0019), in addition to regional recurrence (p = 0.0025).
Taken together, these observations indicate that the use of a combination of MUC1/MUC4 can predict outcomes for patients with OSCC. This combination is also a useful marker for predicting regional recurrence. MUC1 and MUC4 may be attractive targets for the selection of treatment methods in OSCC.
MUC1和MUC4均为高分子量糖蛋白,在包括口腔鳞状细胞癌(OSCC)在内的许多人类上皮癌中,它们都是预后较差的独立指标。然而,目前尚无关于MUC1和MUC4共表达在OSCC中的临床重要性的研究。本研究的目的是评估MUC1/MUC4的共表达情况,并分析其在OSCC中的预后意义。
我们采用免疫组织化学方法检测了206例OSCC患者肿瘤组织中MUC1和MUC4的表达情况。对MUC1/MUC4的共表达情况及其在OSCC中的预后意义进行了统计学分析。
MUC1和MUC4的过表达彼此高度相关(p < 0.0001),MUC1和MUC4表达同时出现是肿瘤侵袭性的有力指标,如肿瘤大小(p = 0.014)、淋巴结转移(0.0001)、肿瘤分期(p = 0.006)、弥漫性浸润(p = 0.028)和血管浸润(p = 0.014)。MUC1/MUC4双阳性患者的总生存期和无病生存期最差。多因素分析显示,MUC1/MUC4双阳性是总生存期和无病生存期的强大独立预后因素(p = 0.007和p = 0.0019),此外还是区域复发的独立预后因素(p = 0.0025)。
综上所述,这些观察结果表明,联合使用MUC1/MUC4可以预测OSCC患者的预后。这种联合也是预测区域复发的有用标志物。MUC1和MUC4可能是OSCC治疗方法选择中具有吸引力的靶点。