The aim of this study was to investigate putative progression markers in cells from normal and dyskariotic cervical smears. Specifically, the pattern of cytokeratin expression in normal and abnormal cervical cells was investigated using well characterised monoclonal antibodies, and the role and prevalence of Epstein-Barr virus (EBV) in the cervix was determined using the Polymerase Chain Reaction (PCR). Cytospin prepared from cells from normal cervical smears were stained using the APAAP method with monoclonal antibodies to specific cytokeratins. No meaningful results were obtained, and the pattern of expression of cytokeratins within cells from smears found to be normal and satisfactory could not be determined. No investigations of abnormal smears was undertaken. DNA was extracted from cells obtained from cervical smears and assayed by PCR of the presence of EBV. Overall the prevalence of EBV in the adult uterine cervix in the NE of Scotland was determined to be 42.8%. A total of 200/467 patient samples, investigated for the presence of EBV, were positive. Of these 98/235 (41.7%) were Control patients, 59/151 (39.1%) were Birthright patients, and 43/81 (53%) were Colposcopy patients. When the 98/235 (41.7%) Normal (Control group) and 102/232 (43.9%) Abnormal (Birthright and Colposcopy group) patients were compared, no significant differences (p=0.05) were observed in positivity to EBV. These results would seem to preclude a primary role in carcingenesis for Epstein-Barr virus, but does not exclude its role as a promoting agent for further events leading to carcinoma of the cervix.

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.

No description available.

Colorectal carcinoma arises through sequential genetic changes whereby an adenoma develops from normal colonic epithelium and then becomes a carcinoma. Critical to this process is two forms of mutually exclusive genomic instability ?? chromosomal instability (CIN) and microsatellite instability (MSI). The colorectal tumours that develop from each of these pathways have distinct pathological and molecular differences. Most MSI+ colorectal carcinomas are associated with the CpG island methylator phenotype (CIMP) - an epigenetic phenomenon where a specific and consistent group of genes are silenced through promoter methylation. However, over half of fall CIMP+ colorectal tumours are microsatellite stable (MSS). It is well known that the WNT/β-catenin signalling pathway is instrumental in the initiation and development of CIN type tumours but it is less clear whether this pathway has any significant involvement in MSI+ or methylated tumours. The role of the PI3K1AKT signalling pathway in the development of solid human tumours has only recently been established and the affects of abnormal PI3K/AKT signalling in sporadic colorectal carcinomas is yet to be fully elucidated. The objective of this thesis was to investigate the involvement of the WNT/β-catenin and PI3K/AKT signalling pathways in the CIN, MSI+ and methylated subgroups of sporadic colorectal carcinoma. To achieve this, the expression patterns of β-catenin, p-AKT and PTEN were identified by immunohistochemistry on sections from tissue microarrays consisting of cores from a large group of sporadic colorectal carcinomas. Each of these proteins is an integral part of the constitutive activation of WNT/β-catenin or PI3K/AKT signalling and their expression patterns were correlated with the clinical, pathological and molecular characteristics of the different subgroups of colorectal carcinoma. Increased nuclear β-catenin expression, an indicator of activated WNT signalling, is associated with MSS and the pathological features of CIN type tumours and inversely associated with the pathological and molecular features of MSI+ and CIMP+ tumours. In all forms of sporadic colorectal carcinoma, nuclear β-catenin expression was not an indicator of overall survival. PTEN was not associated with any particular subgroup of sporadic colorectal carcinoma, but decreased cytoplasmic expression was indicative of overall worse outcome, especially in MSS or CIN type tumours. While the identification of nuclear β-catenin in sporadic colorectal carcinomas is not a satisfactory prognostic marker, the immunohistochemical detection of absent PTEN expression may prove useful in identifying poor outcome in individuals with sporadic MSS colorectal carcinoma.

Diss. (sammanfattning) Stockholm : Karol. inst. / Härtill 5 uppsatser.

Diss. (sammanfattning) Stockholm : Karol. inst. / Härtill 6 uppsatser.

Diss. (sammanfattning) Stockholm : Karol. inst. / Härtill 5 uppsatser.

Diss. (sammanfattning) Stockholm : Karol. inst. / Härtill 5 uppsatser.

Diss. (sammanfattning) Stockholm : Karol. inst. / Härtill 6 uppsatser.

Diss. (sammanfattning) Stockholm : Karol. inst. / Härtill 5 uppsatser.