Rehman, S.; (2005) A study of the molecular pathology of ductal carcinoma in situ and invasive ductal carcinoma of the breast. Doctoral thesis , University of London.

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Abstract

The biological validity of the histopathological classification of ductal carcinoma in situ (DCIS) of the breast was evaluated in this study by correlating the three histopathological grades of DCIS to immunohistochemical expression of Ki67, p53, cerbB-2, markers of poor prognosis in invasive ductal carcinoma (IDC) and also to bcl2 and ER, markers of good prognosis in invasive breast cancer. DCIS grades correlated positively to Ki67, p53, cerbB-2 and negatively to bcl2 and ER, suggesting validity of the classification. The incidence of bax protein expression was determined immunohistochemically in DCIS and IDC. It did not correlate to histopathological grades of DCIS or IDC. The relationships of bax protein to the above mentioned biological markers were also determined in DCIS and IDC. Furthermore, the expression of bax, bcl2, Ki67, ER, p53 and cerbB-2 within DCIS grades was compared with the expression of these markers within IDC grades. The DCIS grades were determined subjectively as well as objectively by means of computer assisted image analysis with significant correlation found between subjective and objective measures. Image analysis was also used to determine percentage of positive cells per case for the nuclear stains (Ki67, ER, p53). Immunohistochemically positive p53 cases were analysed for p53 mutation by polymerase chain reaction (PCR) and subsequent DNA sequencing to compare the incidence of p53 mutation in DCIS to that of IDC. Biochemical changes within tissue may either initiate disease or occur as the result of the disease process and these changes can be studied by both Fourier transform infrared (FTIR) and FT-Raman spectroscopic techniques. FTIR and FT-Raman were employed to distinguish the DCIS and IDC grades. It has the potential to distinguish between DCIS grades, between IDC grades and also between DCIS and IDC as whole groups. The implications of the obtained data for the understanding of the molecular biology of DCIS of the breast and IDC are discussed and future investigations to further elucidate the molecular and cellular mechanisms involved are proposed.

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