| Background Recently, The incidence of Non-melanoma skin cancer(NMSC) has increased,Squamous cell carcinoma(c SCC) is the second most common of NMSC after basal cell carcinoma(BCC). Many researchers have studied the mechanism of the occurrence and progression in c SCC from molecule and cytology level, but the exact mechanism was still unknown. More and more studies have shown that there could exist the cancer stem cells(CSCs) in tumor, and suggesting that it could be the main root of tumor growth, metastasis and resistance to the therapy. Related studies of CSCs started from recognizing the specific bio-markers, and investigating the molecular biology and physiology mechanisms of CSCs in solid tumors, which had promoted the further studies in CSCs. However, there were few studies of CSCs related to c SCC.This study is divided into the following two parts:PartⅠ: CD133 expression status and clinical prognostic value in cutaneous squamous cell carcinomaPurpose To investigate the expression of CSCs marker CD133 in c SCC tissues; To discuss the correlation between CD133 expression and the clinicopathological characteristics of c SCC; To study its effect on clinic prognostic value.Method165 c SCC resected specimens and 30 adjacent nonmalignant epithelial tissues were selected, which were embedded in paraffin. Immunohistochemical method(IHC)was used to evaluate the expression of CD133 on the basic construction of tissue micro-arrays, applying immunoreactive score semiquantitative method to analyse the results. And using ROC curve, K-M curves and Cox proportional hazards regression model analyse the statistics.Result1. The IHC result shows that the expression of CD133 was different in c SCC,and it mainly expressed on cell membrane; Based on the ROC curves, we defined the cutoff score for high CD133 expression as greater than 65% of tumor cells positively stained. High expression of CD133 was observed in 84/165(50.9%) of the c SCC samples and 5/30(16.7%) of the adjacent normal skin tissue samples(P = 0.001).2. As the correlation with the c SCC patients’ clinicopathologic features, it showed that high expression of CD133 was positively correlated with poorly differentiation(P =0.011), and advanced tumor stage(P =0.020).3. In univariate survival analysis, high expression of CD133 was correlated with poor prognosis(P < 0.0001). Moreover, multivariate analysis showed that expression of CD133 was an independent prognostic factor of the c SCC(P = 0.023).Conclusion c SCC tissue CD133 expression was significantly higher than that in normal skin tissue; CD133 expression correlated with clinicopathological features of poor progress of c SCC. In addition, CD133 expression in patients with a poor prognosis c SCC an independent prognostic factor, CD133 clinical staging prognostic evaluation of patients c SCC important clinical significance. The results also suggest that CSC could play a role in the occurrence and development of c SCC.PartⅡ:Cancer stem cell markers CD133 and Oct-4 expression status and their significance in Actinic keratoses, Bowen’s disease and c SCCPurpose To study the expression status of CD133 and Oct-4(CSCs biomarkers) in actinic keratoses(AK), Bowen’s disease(BD) and c SCC, and analyse the differences in their expression.Method41 cases of specimen were selected from First Affiliated Hospital of Sun Yat-Sen University between 2011 and 2015, which were clearly diagnosed by pathologist. There were 18 cases in AK, 15 cases in BD, 8 cases in c SCC. Applying IHC method to evaluate the expression status of CD133 and Oct-4, and calculated the percentage of the postively stained cells.Result1. IHC results showed that the expression status of CD133 were different in three groups, Winyard standard IHC score showed: all scores of AK≤3 points; BD: 4-5points-33.3%(5/15), 6-7 points-6.7%(1/15); c SCC: 2-3 points-50.0%(4/8), each of4-5points and 6-7 points-25%(2/8). The CD133 expression status among three groups were significantly different(P <0.001). The expression among three groups were statistically different and gradually up-regulated; and there was the abnormal expression of CD133 in basal layer of AK and BD, with polar differentiation, and partly expression with clonal proliferation, then it gradually invaded into the upper part or superficial layer of dermal.2. IHC result showed that the expression of Oct-4 was postively stained in nucleus, Winyard standard IHC score showed: the scores of AK、BD、c SCC were ≤5points, but the scores were up-regulated in AK-BD. The expression of Oct-4 in three groups were statistically different(P <0.05), and it was obviously expressed in certain pathology types: Bowen’s AK; moderate-severe atypical hyperplasia BD and poorly differentiation c SCC.Conclusion1. The expression status of CD133 in precancerous lesions AK, carcinoma in situ BD, c SCC were statistically different and gradually up-regulated; and there was the abnormal expression of CD133 in basal layer of AK and BD, with polar differentiation, and partly expression with clonal proliferation, then it gradually invaded into the upper part or superficial layer of dermal.2. The expression of CD133 and Oct-4 in precancerous skin lesions, carcinoma in situ and c SCC, which further suggested that CSCs were play a significant role in the origin, occurrence and progrssion of c SCC. |
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