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 breast cancer as they may complement each other in
predicting the progression of the disease. / published_or_final_version / Pathology / Master / Master of Medical Sciences
| Identifer | oai:union.ndltd.org:HKU/oai:hub.hku.hk:10722/174393 |
| Date | January 2012 |
| Creators | Wu, Pei Hsin., 吳佩欣. |
| Publisher | The University of Hong Kong (Pokfulam, Hong Kong) |
| Source Sets | Hong Kong University Theses |
| Language | English |
| Detected Language | English |
| Type | PG_Thesis |
| Source | http://hub.hku.hk/bib/B47468907 |
| Rights | The author retains all proprietary rights, (such as patent rights) and the right to use in future works., Creative Commons: Attribution 3.0 Hong Kong License |
| Relation | HKU Theses Online (HKUTO) |
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