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

在寻找有助于评价口腔鳞癌远处转移潜能的临床病理因素的过程中，我们得出结论：口腔鳞癌远处转移病例中E-钙粘附素(E-cad)和α连环蛋白(α-CAT)呈阴性表达，pN2b或pN2c淋巴结转移，并对肿瘤化疗耐药。此外，我们先前的研究表明，在鳞癌中，硫酸乙酰肝素糖胺聚糖(HS-GAG)表达增强的病例会导致高淋巴结转移发生率。此外，HS-GAG免疫组织化学染色强阳性的鳞状细胞对联合化疗耐药。考虑到远处转移的发生率与鳞癌对化疗药物的耐受性呈正相关，发展HS-GAG染色强阳性的抗鳞状细胞癌化疗有可能降低远处转移的发生率。另一方面，我们的研究表明，化疗后鳞癌细胞中E-cad和α-CAT的表达水平可能升高，而HS-GAG的表达水平则可能降低。从这里显示的证据来看，即使是在传统的评估系统评估为对化疗耐药的SCC的病例中，SCC的生物学特性在治疗后也可能发生改变，然后这种改变的特征可能会抑制转移潜能。因此，在治疗过程中检测鳞癌的生物学变化，包括E-cad、α-CAT和HS-GAG的表达，可能有助于评估鳞癌的远处转移。

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.