Expression Pattern Of Cancer Stem Cell Markers In Oral Squamous Cell Carcinoma And The Correlation Between Its Pattern And Prognosis

Background:Oral squamous cell carcinoma (OSCC) is one of the most common cancers in oral and maxillofacial malignant tumor, which has high recurrence rate and metastasis rate. In recent years, the current study is focused on cancer stem cell hypothesis, indicated that as candidate CSC markers, CD44, podoplanin and ABCG2 positive cancer cells in vitro shows highly correlated with the growth, metastasis and recurrence of OCSS cancer cells. However, there is a little evidence for the location and distribution of CSC in oral SCC tissue.Objective:In order to develop new treatment strategy targeting on OSCC, we investigated the localization and expression pattern of CD44, podoplanin and ABCG2, which are known as a cancer stem cell marker; and evaluated the possibility of using them as cancer stem cell markers of OSCC for tumorigenesis, histological stage and clinical prognosis.Methods:The Expression of CD44, podoplanin and ABCG2 was investigated by immunohistochemistry in 30 cases of OSCC. Data were analyzed using SPSS version 11.5 for windows.Results:1. The expression and localizationThe tumor cells in 28(93.33%) of the 30 specimens were positive for CD44. The tumor cells in 24(80%) of the 30 specimens were positive for ABCG2. The tumors cells in 21(70%) of the 30 specimens were positive for podoplanin.(1) Squamous epitheliums:CD44-positive cells localized in the cytoplasm and membrane of both basal layer and spinous layer. Podoplanin-positive cells were observed only in basal cell layer of epithelium above lymphatic vessels; whereas ABCG2 showed strong positive reaction in specific regions of keratin layer.(2) In well differentiated cancer nest; CD44 and podoplanin showed the similar expression pattern of squamous epitheliums. While, ABCG2 expression was observed only in the center of cancer nest. In the basal-like layer and spinous-like layer of invading tumor nests, ABCG2 was low positive expression or no expression. In Stromal lymphocytes, CD44 also showed strong membranous staining. In poorly differentiated cancer nest, CD44, ABCG2 and podoplanin were positive.(3) Chemotherapy cases:CD44, ABCG2 and podoplanin expression localized around the necrosis cancer nest.2. The correlation of CD44, podoplanin and ABCG2 expression to the pathological characteristicsThe expression of CD44 and ABCG2 did not change significantly, there were no significant difference in the expression with the decreasing degree of histological differentiation. While, podoplanin positive rate increased with the decreasing degree of histological differentiation(P<0.05).3. The correlation of CD44, ABCG2 and podoplanin expression to the clinical characteristics(1) The expression of CD44, ABCG2 and podoplanin in gender, age, T stage, therapy and TMN stage showed no significant difference(P>0.05).(2) The expression of ABCG2 and podoplanin protein in lymph node metastasis cases showed significantly higher than those without lymph node metastasis cases(P<0.05).Conclusions:1. As cancer stem cell markers, the expression of ABCG2 and podoplanin were significantly correlated with lymphatic metastasis. Meanwhile, after chemotherapy, CD44 and podoplanin positive cells showed overlap, suggest that CD44 and podoplanin could be used as a clinical prognostic indicator in further research.2. The expression of podoplanin showed highly correlated with tumor differentiation; while, CD44, podoplanin and ABCG2 positive cells showed highly overlap in poorly differentiated cancer nest, suggest that these cancer stem cell markers may be important factors related to tumor differentiation of OSCC.