Extranodal Extension and Epithelial Cell Adhesion Molecule Over-expression in Oral Squamous Cell Carcinoma.

BACKGROUND/AIM: Concomitant chemoradiotherapy (CCRT) with cisplatin is commonly administered after neck dissection in patients with oral squamous cell carcinoma (OSCC) showing extranodal extension (ENE). This study investigated whether the efficacy of CCRT differed depending on the degree of ENE and whether the expression of epithelial cell adhesion molecule (EpCAM) was associated with prognosis. PATIENTS AND METHODS: Patients with OSCC who underwent neck dissection and had histologically proven neck metastasis (pN+) were investigated retrospectively. ENE was divided into ENE minor (ENEmi; <2 mm) and ENE major (ENEma; ≥2 mm). The expression of EpCAM was also immunohistochemically examined using tissues obtained during neck dissection. RESULTS: One hundred and seventy pN+ cases [ENE(-), n=89; ENEmi, n=23; ENEma, n=58] were included. Multivariate analysis revealed that advanced T stage and ENEma were significantly correlated with poor prognosis. The 5-year disease-specific survival rates in ENE(-), ENEmi, and ENEma groups were 73.7%, 75.5%, and 28.0% respectively. An add-on effect of postoperative CCRT was not seen in the ENEmi group; however, postoperative CCRT improved the survival of patients in the ENEma group. In the ENEma group, the prognosis was significantly worse in EpCAM-positive patients than in EpCAM-negative patients. CONCLUSION: Postoperative CCRT may improve prognosis in ENEma cases. EpCAM expression may be a poor prognostic factor in ENEma cases. On the other hand, postoperative CCRT did not have a significant effect on prognosis in ENEmi cases. Among them, although there was no significant difference in the survival rate, postoperative CCRT could be omitted in ENEmi/EpCAM(-) cases.

Cell-in-cell structure in cancer: evading strategies from anti-cancer therapies.

One of the regulated forms of cell death is the cell-in-cell (CIC) structure, in which a surviving cell is engulfed by another cell, a mechanism that causes the death of the engulfed cell by an adjacent cell. Several investigators have previously shown that the presence of CICs is an independent risk factor significantly associated with decreased survival in patients with various types of cancer. In this review, we summarize the role of CIC in the tumor microenvironment (TME), including changes and crosstalk of molecules and proteins in the surrounding CIC, and the role of these factors in contributing to therapeutic resistance acquisition. Moreover, CIC structure formation is influenced by the modulation of TME, which may lead to changes in cellular properties. Future use of CIC as a clinical diagnostic tool will require a better understanding of the effects of chemotherapy on CIC, biomarkers for each CIC formation process, and the development of automated CIC detection methods in tissue sections of tumor specimens.

CD44 Variant 6 Expression and Tumor Budding in the Medullary Invasion Front of Mandibular Gingival Squamous Cell Carcinoma Are Predictive Factors for Cervical Lymph Node Metastasis.

Oral squamous cell carcinoma (OSCC) with invasion into the mandibular medullary space has been reported to be a predictive factor for cervical lymph node metastasis (CLNM). As CLNM has been associated with the stemness of cancer cells, we aimed to evaluate the relationship between clinical characteristics and immunohistochemical findings on the invasion front of the medullary invasive OSCC and CLNM. The medical records of 25 patients with the mandibular medullary invasive OSCC who were performed mandibulectomy and neck dissection in our department from 2010 to 2016 were examined. Serial sections were stained with antibodies against CD44 variant 6 (CD44v6) to examine cancer stemness and to evaluate the number of tumor buds in the medullary invasion front of the mandibular invasive OSCC. Categorical data were analyzed by Fisher's exact test. The expression of CD44v6 and the number of tumor buds between the groups with and without pathological CLNM (CLNM+ and CLNM-, respectively) were analyzed using the Mann-Whitney U test. Of the 25 patients, 11 patients were CLNM+. Of the several measured variables, histologic differentiation of the mandibular invasive OSCC was a significant factor for CLNM+. CD44v6 expression and tumor bud formation in the medullary invasion front of the mandibular invasive OSCC were significantly higher in the CLNM+ group, suggests that both CD44v6 and tumor budding in the medullary invasion front are predictive factors for CLNM.