An evaluation system of distant metastasis of oral squamous cell carcinoma according to the biological alterations in the course of cancer treatment

在研究口腔鳞状细胞癌（SCC）远处转移潜能的临床病理因素的过程中，我们得出结论，远处转移病例在SCC细胞中表现为E-cadherin （E-cad）和α catenin （α-cat）的阴性表达，pN2b或pN2c淋巴结转移，对癌症化疗有抵抗。此外，我们之前的研究表明，硫酸肝素糖胺聚糖（HS-GAG）在SCC中表达增强的病例导致淋巴结转移的发生率高。此外，我们还发现HS-GAG免疫组化株强阳性的SCCs对蒽环类、顺铂类和培霉素类联合化疗具有耐药性。考虑到远端转移的发生率与SCC对肿瘤化疗的耐药特性呈正相关，开发针对HS-GAG染色强阳性SCC有效的肿瘤化疗方案可能会降低远端转移的发生率。另一方面，我们的研究表明，癌症化疗后SCC细胞中E-cad和α-cat的表达水平可升高，而HS-GAG在癌中的表达水平可降低。从这里显示的证据来看，即使在一个被常规评估系统评估为化疗耐药的SCC病例中，治疗后SCC的生物学特性可能会被改变，然后改变的特性可能会抑制转移潜力。因此，在治疗过程中检测SCC的生物学变化，包括E-cad、α-cat和HS-GAG的表达，可用于评估SCC的远处转移。

During the course of studies to identify clinicopathological factors which might be useful in evaluation of distant-metastatic potential of oral squamous cell carcinoma (SCC), we have reached the conclusion that distant metastasis cases showed negative expression of E-cadherin (E-cad) and α catenin (α-cat) in the SCC cells, pN2b or pN2c lymph node metastasis, and resistance to the cancer chemotherapy. Moreover, our previous studies revealed that cases showing enhanced expression of heparan sulfate glycosaminoglycan (HS-GAG) in SCC caused high incidence of lymph node metastasis. In addition, it was also revealed that the SCCs strongly positive for the HS-GAG immunohistochemical straining were resistant to the combined chemotherapy with anthracycline, cisplatin and peplomycin. Considering the positive relationship between the incidence of distant metastasis and the character of SCC resistant to the cancer chemotherapy, it might be possible that development of cancer chemotherapy effective against SCC strongly positive for the HS-GAG staining could reduce the incidence of the distant metastasis. On the other hand, our studies suggested that the expression level of E-cad and α-cat in the SCC cells could be increased after the cancer chemotherapy while the expression level of HS-GAG in the carcinoma could be deceased. From the evidence shown here, even in a case evaluated as a resistant SCC to the chemotherapy by conventional evaluation system, it might be possible that biological character of the SCC could be altered after the treatment, and then the altered character could suppress metastatic potential. Consequentially examination of the biological alterations of SCC including expression of E-cad, α-cat and HS-GAG during the course of the treatment could be useful in evaluation of distant metastasis of SCC.