Prognostic Factors in Breast and Colorectal Cancer.

This thesis describes the characterisation of the expression of tumour associated proteins in a wide range of breast and colorectal lesions and the application of these observations to some specific clinical problems. Immunohistochemistry was the method of choice for these studies. Ki67, a proliferation associated antigen was studied using the MEB1 antibody and Heat Shock protein 27 with the D5 antibody. ER and p53 proteins were assessed with their respective antibodies and three CD44 proteins were studied using antibodies CD44H, CD44v3 and CD44v6. Optimal methods for staining and the assessment of the staining pattern for each antibody have been developed and are discussed. Variations in the expression of these proteins between benign and malignant lesions and at different stages of tumour progression were determined. Clinical problems of differentiating between metastasising and non-metastasising low grade breast carcinomas and between recurring and nonrecurring colorectal carcinomas at both Dukes' B and Dukes' C stages of tumour progression are addressed. MIB1 was found to be useful for the distinction between benign and malignant lesions in both breast and colorectal studies and D5 for breast carcinomas. Maximum CD44H levels of expression were found in benign lesions with a decrease in expression manifest at the metastatic stage of tumour progression. CD44H was found to be a useful antibody for the distinction between non-metastasising and metastasising lesions of Gradel breast carcinomas and between non-recurring Dukes' B carcinomas and those that showed metastatic, but not local, recurrence. No differences in CD44H staining could be found between recurring and non-recurring Dukes' C carcinomas but differences in p53 staining were found at this stage of tumour progression. The staining pattern of ER over the range of pathological lesions studied was complex, but its role as both a predictive and prognostic factor is discussed