| Objective: Squamous cell carcinoma(SCC), also known as Epidermoid Carcinoma, is an aggressive tumour that occurs in the epidermis and adnexal keratinocytes(KC)and can proliferate to and invade the deeper tissue. In terms of incidence rate, the SCC is a malignant skin tumour that has an incidence rate only second to that of the base cell carcinoma. The superfamily of Transforming growth factor –β(TGF-β) consists of a variety of proteins involved in the regulation of various human physiological and pathological processes. It can mediate the body’s growth and development, such as embryonic development, angiogenesis, wound healing, and tumorigenesis. Studies have confirmed that the TGF-β / Smads signalling pathway can inhibit cell proliferation and hence is closely related to skin cancer. The Nodal embryonic morphogens, an important member of the TGF-β superfamily, exist normally only in human fetal tissue and embryonic stem cells, with their expression reduced as the tissue goes to mature. As a result, the Nodal is not expressed in normal adult tissues. In recent years, the Nodal protein is detected in a variety of malignant tumours such as the malignant melanoma, breast cancer, stomach cancer, and the prostate cancer. It has been further found that there is a positive correlation between the degree of the malignancy of tumours and the expression of the Nodal protein. The transcription intermediary factor 1-γ(TIF1-γ), a member of the family of transcription intermediary factors, is a secondary factor of the TGF-β signalling pathway and is involved in the regulation of various physiological processes of the body. The TIF1-γ contributes to the presence of tumours by reducing the activity of the Smad4 molecules, limiting the expression of the genes related to the anti-proliferation of cells on the TGF-β pathway, and preventing the functioning of cell anti-proliferation. According to Dupont, during the early development of the ectoderm, the expression of TIF1-γ can inhibit the Nodal signalling pathway. This experiment examines the expression states of the Nodal and TIF1- γ in normal tissues and in different classes of SCC tissues, using the method of immunohistochemistry. We also investigate the correlation between the expressions of the two, their relationship to SCC and pathological features and clinical stages, and the role of the two in the development of the SCC. Methods: On a basis of pathological diagnosis, we select 65 cases of SCC specimens with complete paraffin blocks and associated clinical data from the Dermatology of Luzhou Medical College between January 2007 and June 2014. We group these cases into three according to the pathological diagnosis, with 30 cases classified as well-differentiated, 20 classified as moderately-differentiated, and 15 as poorly differentiated. All the specimens are from the scalp, face and other exposed parts, without having any laser radiation or other anti-tumour therapy before surgery. We also select as a control group 20 cases of specimens from normal skin tissues that were operated due to craniofacial trauma or cosmetic surgery. We use immunohistochemical staining(ElivisionTMplus two-step) to detect the expression of Nodal and TIF1-γ for each group, and do statistical analysis using SPSS17.0. Any result is considered statistically significant if P <0.05. Results: 1. Nodal analysis: Nodal protein in normal skin tissue is not expressed, with the expression rate being 0%(0/20). In the SCC groups, there are clear brown particles inside the cytoplasm of tumour cells and positive products were mainly distributed in the cytoplasm, with the total positive expression rate being 35.38%(23/65). The positive rates for the well-differentiated group(group 1), the moderately-differentiated group(group 2), and the poorly differentiated group(group 3) are respectively 16.67, 45%, and 60%. The difference between group 1 and 2 is statistically insignificant(P>0.05); the difference between group 2 and 3 is statistically insignificant(P>0.05); the difference between group 1 and 3 is statistically significant(P<0.05). The expression of Nodal have nothing to do with the age and gender of patients.The higher the TNM staging, the higher the positive expression rate of Nodal, and the difference is statistically significant.2. TIF1-γ analysis: TIF1-γ in normal skin showed high homogeneity and a high positive expression of 85%(17/20). The positive staining is localized in the cytoplasm, with nucleus staining visible in a few cases. In the SCC groups, the total positive rate is 56.92%(37/65), with the positive rates for group 1, 2 and 3 being83.33%, 40% and 33.33% respectively. The difference between group 1 and 2 is statistically significant(P<0.05); the difference between group 2 and 3 is statistically insignificant(P>0.05); the difference between group 1 and 3 is statistically significant(P<0.05). The expression of TIF1-γ have nothing to do with the age and gender of patients. The higher the TNM staging, the lower the positive expression rate of TIF1-γ, and the difference is statistically significant. 3. Correlation of Nodal and TIF1-γ in SCC:the Nodal and TIF1-γ expression rates are negatively correlated(r=-0.526). Conclusion: 1.Nodal exhibits universal negative expression in normal skin, partly positive expression in SCC tissues, and the expression of Nodal has nothing to do with the age and gender of patients. As the tumour grade goes up, pulp staining in cells gradually deepens and the positive rate gradually rises, indicating that Nodal may be associated with the degree of differentiation and the TNM staging in SCC. 2. TIF1-γ in normal skin tissue has a super high positive expression rate, but this rate decreases as tumour pathological grade becomes higher and the coloration degree becomes lighter in SCC tissues, and the expression of TIF1-γ has nothing to do with the age and gender of patients. Indicating that TIF1-γ may be associated with the degree of differentiation and the TNM staging in SCC. 3. In the SCC groups, with increasing pathological grade, the Nodal and TIF1-γ expression rates are negatively correlated. |
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