A dysfunctional endometrial renin–angiotensin system (RAS) could aid the
growth and spread of endometrial cancer. To determine if the RAS is altered in
endometrial cancer, we measured RAS gene expression and protein levels in 30 human
formalin-fixed, paraffin-embedded (FFPE) endometrioid carcinomas and their adjacent
endometrium. All components of the RAS were expressed in most tumours and in adjacent
endometrium; mRNA levels of (pro)renin receptor (ATP6AP2),
angiotensin II type 1 receptor (AGTR1), angiotensin-converting
enzyme (ACE1) and angiotensin-converting enzyme 2
(ACE2) mRNA levels were greater in tumour tissue than adjacent
non-cancerous endometrium (P = 0.023, 0.008, 0.004 and
0.046, respectively). Prorenin, ATP6AP2, AGTR1, AGTR2 and ACE2 proteins were
abundantly expressed in both cancerous and adjacent non-cancerous endometrium.
Staining was most intense in cancerous glandular epithelium. One potential target of
the endometrial RAS, transforming growth factor beta-1 (TGFB1),
which is essential for epithelial-to-mesenchymal transition, was also upregulated in
endometrial cancer tissue (P = 0.001). Interestingly,
TGFB1 was strongly correlated with RAS expression and was
upregulated in tumour tissue. This study is the first to characterise the mRNA and
protein expression of all RAS components in cancerous and adjacent non-cancerous
endometrium. The greater expression of ATP6AP2,
AGTR1 and ACE1, key elements of the
pro-angiogenic/proliferative arm of the RAS, suggests that the RAS plays a role in
the growth and spread of endometrial cancer. Therefore, existing drugs that inhibit
the RAS and which are used to treat hypertension may have potential as treatments for
endometrial cancer.
Despite being a well-recognised cause of allergic contact dermatitis with an embargo in many countries around the world, bufexamac is available over the counter in topical preparations in Australia. We present a series of patients who developed severe cutaneous eruptions after the topical application of bufexamac containing preparations to highlight the potential risks of this medication, as well as advocate for the reconsideration of its registration by the Therapeutic Goods Administration in Australia.
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