Expression of Smad2 and Smad7 Proteins in Cutaneous Squamous Cell Carcinomas and its Clinical Significance
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Objective To detect the expression of Smad2 and Smad7 in cutaneous squamous cell carcinomas(SCC) and normal squamous epithelia of skins,analyze the relationship of two Smad expressions in SCC of differentiation grades and clinical stages,thus explore the role of Smad2 and Smad7 in the pathogenesis of SCC.Methods Paraffin-embedded tissue sections containing normal squamous epithelia,well differentiated,moderately differentiated and poorly differentiated SCC were stained by SABC immunohistochemistry technique to detect the expression and location of Smad2 and Smad7.Protein immunoexpression was quantified by image analysis in the context of histopathological parameters.The different expressions of Smad2 and Smad7 among all the tissue sections were compared.Expression of Smad2 and Smad7 in different clinical stages of SCC was also analyzed. Results Expression of Smad2 and Smad7 located in cytoplasm in normal squamous epithelia and SCC of skins.There was statistically significant difference of Smad2 and Smad7 expression between normal skin and SCC(P0.05).Compared with normal group,expression of Smad2 was down-regulated and Smad7 was up-regulated in SCC. Obvious difference of expression of Smad2 demonstrated in stage Ⅰ or Ⅱ compared with stage Ⅲ(P0.05).However,there was no statistic difference of Smad7 though gradually increasing from stage I to stage Ⅲ. Conclusions Down-regulation of Smad2 and up-regulation of Smad7 contribute to relieve the inhibition effect mediated by TGF β of cellular proliferation,which results in losing of cell growth suppression mediated by TGF β and contribute to tumor development or progression.Down-regulation of expression of Smad2,down-stream molecular of TGF β signaling pathway,was associated with invasion and metastasis of SCC.Keywords:
Pathogenesis
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Objective:To investigate the expression of connexin 43 , E-cadherin and its relationship with the biological behavior in oral squamous cell carcinoma(OSCC).Method:SABC method was used to detect the expression of the Cx43 and E-cad in the paraffin-embedded slice of 8 case normal human oral squamous epithelium and 29 case different differentiated oral squamous carcinoma .The expression of Cx43 and E-cad was examined in tongue carcinoma cell line (Tca8113) by immunocytochemistry.Result:In normal oral squamous epithelium the expression of Cx43 and E-cad was typically in the membrane ,but they were aberrantly expressed in cytoplasm in OSCC. There was no difference of the area and gray of Cx43 and E-cad positive spots between the normal epithelium and well-differentiated squamous cell carcinoma(P0.05), but the area of the Cx43 and E-cad positive were obviously reduced in moderately differentiated or poorly-differentiated compared with normal epithelium(P0.05).The significant relationship was observed between low Cx43, low E-cad expression and differentiation, metastasis(Cx43: χ 2=7.42, 12.43, P0.05, P0.01; E-cad: χ 2 =7.79, 9.688, P0.05,P0.01)。There was a positive relationship between the expression of Cx43 and E-cad in same sample(r=0.577,P0.0005).Conclusion: The level of the expression of the Cx43 and E-cad can used as the biological mark of the differentiation and transference of the OSCC.
Squamous carcinoma
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This study was conducted to evaluate the clinical significance of the localization of epidermal growth factor receptor (EGF-r), transforming growth factor (TGF)-alpha, and erbB-2 in the development, progression and prognosis of squamous cell cancers (SCCs) of the lung.The localization of EGF-r, TGF-alpha, and erbB-2 was evaluated immunohistochemically in 60 archival specimens of SCC of the lung and in 60 lung specimens without cancer. To clarify the patterns of expression of EGF-r in these tumors, the patterns of expression of EGF-r in cells in culture were monitored after challenging normal human bronchial epithelial and SCC cell lines with either EGF or TGF-alpha at physiological concentrations.The expression of EGF-r, erbB-2, and TGF-alpha were significantly higher in SCC and associated precancerous lesions than in the normal bronchial epithelium and hyperplastic lesions of noncancer specimens. A statistically significant stepwise increase in expression from uninvolved bronchial epithelium to precancerous lesions to SCC was observed with EGF-r and TGF-alpha. The localization of EGF-r in the cytoplasm (P = 0.04), but not in the membrane (P = 0.20), of SCCs was significantly associated with poor overall survival of subjects. To demonstrate the biological relevance of cytoplasmic expression of EGF-r, we noted that there was a prompt reduction in the membrane expression and a concomitant increase in cytoplasmic expression of EGF-r after adding either EGF or TGF-alpha to the cell culture medium. Overall, the study identified an involvement of EGF-r and TGF-alpha in the development of SCCs. The prognostic importance of EGF-r expression in the cytoplasm of lung cancer probably is an indication of the prognostic importance of trafficking of the EGF-r receptor between the Golgi apparatus and cell membranes and of internalization of EGF-r after an interaction with one of the EGF-r ligands at the cellular membrane surface.
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Background: Changes in epithelial cell interactions have been implicated in carcinogenesis, tumour invasion and metastasis. Aim: To screen for altered expression of epithelial adhesion genes in lung cancer development. Methods: Gene expression profiles were assessed with cDNA expression arrays in eight non-small cell lung cancer (NSCLC) and eight normal bronchi obtained from the same patient. Immunohistochemistry (IHC) and RNA in situ hybridisation (ISH) were used to confirm the most prominently expressed adhesion molecules and to investigate their distribution at protein and mRNA levels. Results: 43 differentially expressed cancer-related genes were identified in adenocarcinoma, squamous cell carcinoma (SCC) and normal bronchus. Five of these genes are related to epithelial adhesion—that is, integrin α3 (ITGA3), integrin β4 (ITGB4), desmoplakin I and II (DSP), plakoglobin, and desmocollin 3 (DSC3). ITGA3 and ITGB4, showing predominantly cell–matrix staining, were up regulated in adenocarcinoma and SCC, respectively. ITGB4 also showed strong staining in SCC with IHC and ISH. Components of the desmosome adhesion complex DSP, plakoglobin and DSC3 were strongly up regulated in SCC and showed a distinct cell–cell staining pattern. DSP and plakoglobin were predominantly present at central, more differentiated tumour cells, whereas DSC3 showed a stronger staining in the peripheral basal cells of SCC tumour areas. Conclusions: Lack of cellular adhesion may have an important role in the metastatic potency of a primary tumour. A possible association of strong presence and normal-distributed desmosomal molecules in SCC with the less frequent and late pattern of metastasis in SCC as compared with adenocarcinoma is suggested.
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Objective To examine the expression of CD44 in oral squamous cell carcinoma.Methods Samples of 22 oral SCC and their neighboring incised mucosa were collected and immunohistochemically stained for the expression of CD44.CD44 expression in lesions with different differentiation was compared and analyzed.Results CD44 was expressed in basal and some prickle layer cells of normal mucosa and strongly expressed in lymphocytes as well.The expression of CD44 varied with different differentiation of the SCC tissues,presenting down-regulation in the poor differentiated tissues.Conclusion CD44 could be used as one of the markers for the malignant degree of the oral squamous cell carcinoma.
Oral mucosa
Basal (medicine)
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Epidermoid carcinoma
Interstitial collagenase
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BACKGROUND Abnormality of cell cycle regulators and tumor suppressors, such as cyclin dependent kinase inhibitors (cdkIs), has been reported in malignant tumors. The current study was undertaken to examine the involvement of a cdkI, p27Kip1 (p27), in the neoplastic process of the uterine cervical epithelium. METHODS Immunohistochemical staining of p27 was performed in samples of normal cervical tissue (30 samples), cervical intraepithelial neoplasias (CINs; 17 samples), and invasive squamous cell carcinoma (SCC; 25 samples). The results were compared with the expression levels of Ki-67, cdk2, and cyclin E. The functional aspects of the p27 protein, such as its ability to bind to cdk2 and the phosphorylation activity of p27-bound cdk2, also were evaluated with an immunoprecipitation and histone H1 kinase assay. RESULTS In normal cervical epithelia, the expression of p27 was strong in the intermediate and superficial cells but very weak in the parabasal cells. In CIN samples, the expression of p27 was negligible. The expression of p27 in these tissues showed an inverse topologic correlation to that of Ki-67, cdk2, and cyclin E. However, it is noteworthy that the number of p27 positive cells increased in SCC samples that also showed increased expression of Ki-67, cdk2, and cyclin E. The p27 protein in SCC samples was bound to cdk2 and cyclin E. However, cdk2 that was bound to p27 still possessed histone H1 kinase activity. CONCLUSIONS The expression of p27 may be involved in the growth regulation of the normal squamous epithelium in the uterine cervix. However, aberrant function of p27 expression may occur in invasive SCC of the cervix. Cancer 2001;92:3005–11. © 2001 American Cancer Society.
Cyclin E
Squamous carcinoma
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[Objective] To research P120ctn,β-cat and E-cad protein expression and biologic significance in squamous cervical carcinoma(SCC).[Methods] Expression of P120ctn,β-cat and E-cad protein were examined in normal cervical epithelia and SCC by immunohistochemical staining(SP method).[Results] ①In the normal cervix tissue,P120ctn,β-cat,E-cad were found expression at cell membrance,rarely in endochylema;In SCC P120ctn,β-cat, E-cad were expressed in endochylema,few expressed in cell membrance;β-cat showed nuclear expression,Abnormal expressions of three portions correlated with tumor differentiation status and lymph node metastasis ②P120ctn abnormall expression correlated positively with β-cat and E-cad expressions significantly.[Conclusion] Abnormal expression of P120ctn and related proteins may be useful markers for diagnosis and provide an objective fact for assessing development and metastasis of SCC.
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