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This dissertation, The Expression of Transcription Factors TWIST and Snail in Breast Cancer by Pei Hsin, Wu, 吳佩欣, was obtained from The University of Hong Kong (Pokfulam, Hong Kong) and is being sold pursuant to Creative Commons: Attribution 3.0 Hong Kong License. The content of this dissertation has not been altered in any way. We have altered the formatting in order to facilitate the ease of printing and reading of the dissertation. All rights not granted by the above license are retained by the author. Abstract: Breast cancer comprises of 22.9% of all cancers worldwide in females. In the year 2008, it has caused 458,503 deaths worldwide. De-regulation of transcription factors has been shown to play an important role in the progression of breast cancers. Snail and TWIST genes have been found to promote epithelial-mesenchymal transition (EMT). It has been suggested that the level of expression of each of these genes correlates with poor prognosis in different types of solid tumors. For breast cancer, the up-regulation of Snail was associated with recurrence and higher tumor grade, while the up-regulation and up-regulation of TWIST was associated with shorter survival and metastatic development. However, in recent studies conflicting results have been observed. Our collaborator had analyzed mRNA expression data obtained from the Gene Expression Omnibus (GEO) database together with patient survival data from the breast cancer cohort datasets, and found that expression of Snail when stratified against TWIST expression levels or vice versa, gave more significant association with survival than when expression levels of Snail or TWIST was considered on their own. To investigate whether these findings could be demonstrated at a protein level, we performed imrnuno-histochemisty analysis on breast cancer samples in tissue microarray blocks. Nuclear and cytoplasmic scores of TWIST were successfully assessed separately in 114 invasive breast cancer patients. The Snail scores were obtained from previous studies. As Snail and TWIST are both transcription factors, nuclear expression of each was examined for correlation of Snail and TWIST with pathological features and patient survival. Our results showed that nuclear Snail expression did not correlate with survival (p=0.498) but when stratified with nuclear TWIST, high levels of nuclear Snail expression associated with poorer survival in patients with low nuclear TWIST expression (p=O.2l2), though not statistically significant which agreed with the mRNA results of our collaborator. For nuclear TWIST expression, association with survival was in reverse from that of the mRNA findings. Low expression levels of TWIST mRNA was associated with shorter survival, however immuno-histochemistry showed that high levels of nuclear TWIST expression marginally correlated with poorer survival (p=O.079). Low levels of cytoplasmic TWIST expression on the other hand, correlated with poorer survival in patients (p=O.024), and when stratified against high nuclear Snail, expression was associated with shorter survival (p=O.022), which is in keeping with mRNA findings. The results show that Snail and TWIST expression gave more prognostic value when considered together than when considered individually, which suggests that Snail and TWIST might be functionally similar in the promoting of EMT mediated breast. It also highlights the importance of nuclear and cytoplasmic localization by immuno-histochemistry in evaluating results and in assessing its role in promoting breast cancer progression. In conclusion Snail and TWIST should be considered together for prognostication of b

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