Enhanced Expression of Podoplanin in Oral Carcinomas in situ and Squamous Cell Carcinomas

Abstract

Objective: Podoplanin, a known lymphatic endothelial cell marker, has been reported to be expressed in various types of cancer. To elucidate the expression of podoplanin in precancerous lesions, we examined the immunohistochemical profiles of podoplanin in oral squamous epithelial lesions. Method: We studied a total of 298 foci of squamous cell carcinoma (SCC), carcinoma in situ (CIS), epithelial dysplasia, and hyperplastic and/or normal epithelial lesions by immunohistochemistry using D2-40. Results: There was no positivity for podoplanin in normal or hyperplastic epithelia, while all of the CIS and SCC foci stained positive. Approximately one third of the mild dysplasia foci (10 of 36 foci, 28%) and 80% of moderate dysplasia foci (78/98) showed grade 1 positive reactions (positive only in the 1st layer). Grade 2 reactions (up to 4th layer) were seen in 4 of 98 moderate dysplasia foci (4%), 29 of 74 CIS foci (39%), and 3 of 30 SCC foci (10%). Grade 3 reactions (to more than 5th layer) were found in 35 (47%) CIS foci and 26 (87%) SCC foci. Conclusions: The relationship between the present histological categorization and podoplanin grade was statistically significant. D2-40 expression is considered to be related to the severity of oral precancerous lesions.

Podoplanin-mediated cell adhesion through extracellular matrix in oral squamous cell carcinoma

“…These in vitro results also reflected in the tissue-level observation that PDPN þ cells tended to locate in the basal or peripheral zone of SCC cell nests, in which Ki-67 þ -proliferating cells were not always simultaneously overlapped. 13 In addition, there was no involvement of PDPN in the apoptotic process of oral SCC cells. Although PDPN þ SCC cases were clinicopathologically related to their degrees of differentiation and lymphatic invasion, we did not extend our experiments to include cellular differentiation and lymphatic invasion in this study.…”

“…[5][6][7][8][9]34 In oral cancer, PDPN expression has been related to poor clinical outcomes, including lymph node metastasis or to malignant transformation of precancerous lesions, although its molecular function has not been well understood. [10][11][12][13]35 To elucidate its function, we carried out comparative immunohistochemical studies between PDPN and the other molecules, which are related to cell proliferation or differentiation in oral mucosal malignancies 13 or odontogenic tumors. 7 Its expression profile in oral CIS was almost identical to that of SCC, and the immunohistochemistry for PDPN was helpful in the differential diagnosis of CIS from epithelial dysplasia.…”

“…7 Its expression profile in oral CIS was almost identical to that of SCC, and the immunohistochemistry for PDPN was helpful in the differential diagnosis of CIS from epithelial dysplasia. 13 In odontogenic tumors, its immunolocalization pattern was related to intraepithelial signaling pathways of ECM molecules. 7 In both instances, the area of PDPN distribution overlapped with Ki-67 or PCNA þ areas but was not always identical to them.…”

“…[10][11][12] We have also shown the PDPN expression profiles to be a useful immunohistochemical aid in the differential diagnosis of oral carcinoma in situ (CIS) from epithelial dysplasia because PDPN positive ( þ ) cells are distributed more widely in CIS than in epithelial dysplasia, overlapping with Ki-67 þ -proliferating cell zones. 13 In order to provide a background to the cellproliferating potentials of oral CIS, we have demonstrated the characteristic intercellular deposition and turnover of perlecan, one of the extracellular matrix (ECM) molecules, which results in the widening of intercellular space of the epithelial compartment. [14][15][16] In addition, we have reported that PDPN þ cells are characteristically localized within odontogenic tumor-specific architectures, in which ECM signaling seems to be enhanced.…”

“…20 Hence, the actual molecular function of PDPN in cancer cells has remained largely unknown. In our previous studies, we have paid attention to the characteristic expression mode of PDPN on the cell border or the basolateral surface of tumor cells, 7,13 and we have formulated the hypothesis that PDPN has a role in tumor cells' communication with ECM or ECMmediated cell adhesion. In the present study, we have attempted to examine the function of PDPN by RNA interference (RNAi) with a special reference to cell adhesion and its relationship with the other ECM-signaling molecules using oral SCC cells.…”