Determination of Immunohistochemical Markers for Oral Squamous Cell Carcinoma Invasions

Abstract

Carcinomas are characterized by invasion of malignant cells into the underlying connective tissue and migration of malignant cells. The cellular differentiation of the invasion site as well as the pattern of invasion is crucial for the tumor behavior. Both resection margins and the pattern of invasions are important predictors of local recurrence and survival in surgically treated patients. Therefore, surgical margins should be free from carcinoma or dysplasia after surgical intervention and the accepted definition of a close margin is tumor within 5 mm of the inked resection margin, but has not so clear yet. Others use less than 2 mm or 3 mm within one high power field or a variable definition related to the pattern of invasion at the tumor host interface. The aim of this study was to determine the immunohistochemical markers for identification of invasion pattern of oral squamous cell carcinoma (OSCC) and detection of epithelial cells of surgical margins. The study analyzed the immunohistochemical characteristics of 32 cases : 8 cases each of carcinoma in situ (CIS), OSCC border, OSCC early invasion and OSCC front using Ki-67, p53, CK 17, CK 13, laminin -5γ2 and type IV collagen. The correlation between the morphological pattern on invasive sites and immunohistochemical staining were studied. The results were obtained as follows :1)The average number of Ki-67 positive basal cells was 22.7% in CIS, 57.5% in OSCC border, 62.0% in OSCC early invasion and 60.2% in OSCC front, respectively. The percentage of immuno-positive cells in OSCC border, OSCC early invasion and OSCC front are significantly higher than those of CIS (p<0.05). p53 appeared in almost all tumor cells and highest in OSCC front.2)CK 17 was positive and strong in superficial cells of OSCC border, parabasal cells of OSCC early invasion and pearl nests of OSCC front, although the degree of positivity was variable. It was negative to discrete positive in CIS.3)CK 13 was positive in superficial and parabasal cells of CIS and pearl nests of OSCC front, negative in basal cells of CIS and OSCC early invasion, and weakly present in variable distribution in OSCC border.4)The cytoplasmic accumulation of laminin -5γ2 expression was intense in OSCC border, moderate in OSCC early invasion and OSCC front, and discrete in CIS.5)Type IV collagen was strong in both OSCC border and OSCC early invasion and weak in CIS and OSCC front.These results suggested that the combined expression of Ki-67 and p53 confirmed the proliferative and mutational activities of these OSCC invasions in contrast to CIS. CK 17 and CK 13 biomarkers detected their histological differentiation and variation in epithelial cells. The migration-promoting activity and role in cancer invasion were regulated by laminin -5γ2 and type IV collagen, and was clearly observed in OSCC border. The present study also revealed high proliferative activity and high invasiveness of epithelial cells in OSCC border similar to cancer and the combined used of the markers for safety margins should be considered important by surgeon.