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）远处转移的临床病理学因素过程中，我们发现：远处转移的SCC细胞中E-cadherin（E-cad）和α-catenin（α-cat）表达阴性，有pN 2b或pN 2c淋巴结转移，对化疗耐药。此外，我们以前的研究表明，在SCC中硫酸乙酰肝素糖胺聚糖（HS-GAG）表达增强的病例导致淋巴结转移的高发生率。HS-GAG免疫组化强阳性的SCC对蒽环类抗生素、顺铂和培洛霉素联合化疗耐药。考虑到远处转移的发生率与SCC对癌症化疗的耐药性之间的正相关性，开发针对HS-GAG染色强阳性SCC的有效癌症化疗可能会降低远处转移的发生率。另一方面，我们的研究提示，化疗后SCC细胞中E-cad和α-cat的表达水平升高，而HS-GAG的表达水平降低。从这里显示的证据来看，即使在通过常规评价系统评价为对化疗耐药的SCC的情况下，SCC的生物学特性也可能在治疗后改变，然后改变的特性可以抑制转移潜力。因此，检测SCC治疗过程中E-cad、α-cat和HS-GAG的表达，对判断SCC的远处转移有一定的参考价值。

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.