![Characterisation of the oncogene HER2 in transitional cell carcinoma of the urinary bladder using fluorescent in-situ hybridisation and immunohistochemistry : Is there a role for anti-her2 therapies? için kapak resmi Characterisation of the oncogene HER2 in transitional cell carcinoma of the urinary bladder using fluorescent in-situ hybridisation and immunohistochemistry : Is there a role for anti-her2 therapies? için kapak resmi](/client/assets/d79c3e4af2b6d196/ctx/images/no_image.png)
Characterisation of the oncogene HER2 in transitional cell carcinoma of the urinary bladder using fluorescent in-situ hybridisation and immunohistochemistry : Is there a role for anti-her2 therapies?
Başlık:
Characterisation of the oncogene HER2 in transitional cell carcinoma of the urinary bladder using fluorescent in-situ hybridisation and immunohistochemistry : Is there a role for anti-her2 therapies?
Yazar:
Latif, Zahid, author.
ISBN:
9780438059238
Yazar Ek Girişi:
Fiziksel Tanımlama:
1 electronic resource (276 pages)
Genel Not:
Source: Dissertation Abstracts International, Volume: 76-08C.
Advisors: Mark Underwood.
Özet:
The HER2 oncogene is located on chromosome 17q and encodes for a 185 kilo-dalton trans-membrane growth factor receptor with intrinsic tyrosine kinase activity. In many human cancers, including transitional cell carcinoma (TCC) of the human bladder gene amplification and protein over-expression of HER2 are associated with a poor clinical outcome. However the exact incidence of HER2 gene amplification and protein over-expression remains unclear. This is because in the literature various different laboratory techniques have been applied without standardisation, each giving different results. For example, if inmiunohistochemistry is used to assess protein over-expression, then depending on the type of antibody and scoring system used, rates of protein over-expression vary from 2-71%. In a similar manner depending on whether solid matrix blotting techniques such as Southern Blotting or Northern blotting, the polymerase chain reaction or Fluorescent in-situ hybridisation (FISH) are used, HER2 gene amplification rates vary from 7-32%. Gene amplification is the most common cause of protein over-expression in breast cancer, a malignancy in which HER2 has been extensively studied. It is therefore important to standardise the laboratory techniques used to assess HER2. This is particularly important if the results of any such laboratory tests are to lead to the development and clinical use of therapeutic agents targeted against the HER2 receptor. Anti-HER2 therapies are being used with increasing frequency in the clinical treatment of many cancers. In breast cancer FISH and immunohistochemistry (using specific antibodies and scoring systems) are approved for assessing HER2 status, with a view to treatment with anti-HER2 antibodies such as trastuzumab, which can specifically target HER2 over-expressing cells and retard their growth. The aim of this thesis was therefore to assess HER2 gene amplification and protein over-expression in TCC of the urinary bladder using FISH and IHC. As a result it was hoped to determine the possible importance of HER2 in terms of tumour growth and patient outcome as well as to determine the potential suitability of anti-HER2 therapies in the clinical treatment of bladder cancer. Two groups of tumours were studied. The first group comprised 75 patients with evidence of TCC that invaded the detrusor muscle at first clinical presentation. The other group comprised 26 pairs of tumours- the first tumour of the pair had evidence of mucosa confined /lamina propria invasive disease and the second tumour had evidence of detrusor muscle invasive disease. Overall there was a high incidence of increased HER2 copy number in all tumours studied. Increased HER2 copy number was seen in 92% (69/75) of the detrusor muscle invasive tumours at first clinical presentation, 73% (19/26) of the tumours with mucosa confined /lamina propria invasive disease and 88% (23/26) of the tumours which had progressed to detrusor muscle invasive disease. There was no significant difference in the HER2 copy number between the 26 mucosa confined /lamina propria invasive tumours compared with those with detrusor muscle invasion. Also there was no significant difference between the 75 detrusor muscle invasive tumours and the 26 tumours that had progressed to detrusor muscle invasion. Similar results were noted for chromosome 17 copy number. Polysomy 17 was observed in 73/75 (97%) of the tumours with detrusor muscle invasion at first presentation, 23/26 (88%) of the 26 tumours with mucosa confined /lamina propria invasive disease and 24/26 (92%) of the 26 tumours that had progressed to detrusor muscle invasive disease. These results suggest that tumours that have not yet acquired the ability to invade into the detrusor muscle (mucosa confined/lamina propria invasive tumours) have similar genetic abnormalities at the HER2 gene locus and chromosome 17 as those tumours that have already invaded into the detrusor muscle. Those 26 tumours with mucosa confined /lamina propria invasive disease and a HER2 copy number higher than the median value had a shorter time to progression to detrsuor muscle invasive disease and a shorter time to death. This suggests that in some tumours, HER2 acts as a negative prognostic factor.
Notlar:
School code: 0547
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Yer Numarası | Demirbaş Numarası | Shelf Location | Lokasyon / Statüsü / İade Tarihi |
---|---|---|---|
XX(684700.1) | 684700-1001 | Proquest E-Tez Koleksiyonu | Arıyor... |
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