The purpose of this study was to investigate several biological markers that may predict the
response of muscle invasive transitional cell carcinoma TCC of the bladder to radical
radiotherapy. The specific markers chosen were tumour angiogenesis (CD31 &CD34),
tumour cell proliferation (Ki-67) and apoptosis (bcl-2), intratumour macrophage infiltration
(CD68) and p53.
Archival formalin fixed paraffin embedded pre treatment bladder biopsies from 101
patients with muscle invasive TCC were obtained. All patients subsequently received
radical radiotherapy as their only treatment for the disease. 4µm sections were graded
according to the WHO grading system and staged by the TNM classification. Angiogenesis
(CD31&CD34) counts were obtained using a 25-point Chalkley eyepiece graticule. Bcl-2
scored as positive and negative, while p53, Ki-67 and CD68 were estimated using an
eyepiece graticule. The medical records were examined to assess the response of the
tumour at the 3-month post radiotherapy cystoscopy and the long-term outcome. Patients
were classified into two groups in two sections: the first section includes (1) those free of
disease (no tumour detected in the bladder at the 3-month cystoscopy), (2) those with
resistant disease (tumour present at 3 months). The second section includes (1) those with
persistent or recurrent cancer in the bladder (tumour recurred after an initial 3 months
negative check cystoscopy together with patients with resistant disease at 3 months), (2)
those free of disease at all subsequent cystoscopies.
Detailed statistical analysis revealed that there were no association between any of the
markers examined and the response to radiotherapy. MVD using CD34 was lower in higher
stage tumours (p=0.050). Females, whilst representing only a small fraction (16) of the total
of patients studied showed an inferior response to radiotherapy when compared to that of
male patients (p=0.048). Higher median haemoglobin levels for the response group
(p=0.031) was observed as well as a positive significant correlation between p53 (L1)
expression and MIB-1 (LI) (r=0.332, p=0.001).
The Kaplan-Meier survival analysis shows that the survival time is significantly better for
those who were exposed longer to radiotherapy (> 33 days) (Log Rank, p=0.0246). There
was a significantly higher survival time for patients who have CD68 higher than 42.4 (log
rank, p=D.036).
The study concluded that none of the selected markers could be used as prognostic value in
determining patients most suitable for radiotherapy as primary treatment with curative
intent for their bladder cancer. The finding of a poorer response in females is worthy of
further study since, hormonal and anatomical influences may be important.
Date of Award | 2002 |
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Original language | English |
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Awarding Institution | |
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STUDIES OF THE RESPONSE OF MUSCLE INVASIVE BLADDER CANCER TO RADIOTHERAPY
Saki, Z. I. (Author). 2002
Student thesis: PhD