Apoptosis in breast cancer: relationship with other pathological parameters.

Abstract

Apoptosis is a frequent phenomenon in breast cancer and it can be detected by light microscopy in conventional histopathological sections or by special staining techniques. The number of apoptotic cells as a percentage of cells present, or the number of apoptotic cells per square millimetre of neoplastic tissue, is usually described as the apoptotic index (AI). In breast cancer, the AI is not related to tumour size, axillary lymph node metastasis or distant metastasis at diagnosis. It is greater in invasive ductal carcinomas than in other histological types. High AI is also related to high histological grade, high nuclear grade, comedo-type necrosis, lack of tubule formation, and dense infiltration of the tumour by lymphocytes. Sex steroid receptor-negative tumours have greater AIs than the sex steroid receptor-positive ones. Aneuploid breast cancers with high S-phase fractions (SPFs) also have high AI values compared with diploid tumours with low SPFs. p53-Positive breast cancers have high AIs, whereas tumours that are Bcl-2 positive have low AIs. The AI shows a strong positive correlation to all direct or indirect indicators of cell proliferation, such as mitotic index and Ki67 immunolabelling. Univariate survival analyses show that a high AI is linked with unfavourable disease outcome in axillary lymph node-negative and -positive breast cancer, but multivariate analyses indicate that AI is not an independent prognostic factor. In conclusion, a high AI is related to malignant cellular features and Endocrine-Related Cancer (1999) 6 13-16 indicators of invasiveness and cell proliferation in breast cancer.

Antiproliferative Effect of Lactobacillus helveticus and Low Dose Gamma Radiation on Mammary Carcinogenesis

“…Apoptosis has been consistently reported to be positively correlated with Ki-67 (Lipponen, 1999). In the present study, tumour growth index was markedly reduced by FM, gamma radiation and combined treatment of FM and gamma radiation.…”

Expression of the PAX2 oncogene in human breast cancer and its role in progesterone-dependent mammary growth

“…Apoptosis is an important aspect of breast cancer pathogenesis that presents a complex and somewhat counter-intuitive picture. The highest rates are seen in the most aggressive, highly proliferative tumors, which were mainly PAX2 negative, while lower grade tumors, which are frequently PAX2 positive (Table 2), have relatively low rates (Lipponen, 1999). If PAX2 does a ect mammary apoptosis, its expression could contribute to the pathogenesis of some breast tumors by blocking apoptosis early in progression or, by its absence during later stages, it could favor the selection of apoptosisresistant cells (Zhang et al, 1998).…”

Expression of oestrogen receptor-β in oestrogen receptor-α negative human breast tumours

“…However, high proliferation in primary tumours prior to treatment, is often associated with high levels of apoptosis (Lipponen et al, 1994;Lipponen, 1999;Parton et al, 2002). Therefore, ERb expression was investigated with respect to a marker of apoptosis, active caspase-3 (Parton et al, 2002).…”