Relationship between c-erbB-2 immunoreactivity and thymidine labelling index in breast carcinomain situ

Barnes, Diana M.; Meyer, John S.; González, Juan Guillermo; Gullick, William J.; Millis, Rosemary R.

doi:10.1007/bf01975438

Cited by 57 publications

(21 citation statements)

References 22 publications

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“…This is the first evidence that, at least in a proportion of cases, the same effect can be demonstrated in vivo following treatment with combination chemotherapy. The c-erbB-2 protein is thought to behave as a constitutively active growth factor receptor, and expression of the oncoprotein has been shown to correlate with cell proliferation as measured by the thymidine labelling index (Barnes et al, 1991). The emergence of cells bearing this oncoprotein after chemotherapy is consistent with the early recovery of a cell population that possesses a growth advantage and is in keeping with the Gompertzian model of increased cell proliferation in smaller tumours.…”

Section: Changes In Oncoprotein Expression After Chemotherapymentioning

confidence: 59%

The effects of chemotherapy on morphology, cellular proliferation, apoptosis and oncoprotein expression in primary breast carcinoma

Rasbridge

Gillett²,

Seymour³

et al. 1994

Br J Cancer

138

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S_ary The use of chemotherapy as a form of primary treatment for breast cancer is increasing and, as a result, more resection specimens contain tumours which have been exposed to cytotoxic drugs. We have studied the effects of chemotherapy on the tumour morphology and various biological features of breast carcinoma in a group of 35 patients. These were a group who responded to treatment in a clinical study of the use of primary chemotherapy designed to reduce tumour bulk prior to surgery. Characteristic morphological changes, temporally related to the administration of cytotoxic agents, are seen. The malignant cells become enlarged with vacuolated cytoplasm and vesicular nuclei containing prominent nucleoli; occasionally the nuclei were angular and hyperchromatic. These features are interpreted as degenerative in nature. In 15 cases sufficient material was present in the pretreatment biopsies to compare the grade of the tumours before and after chemotherapy: changes were found in six tumours. Cytotoxic drugs do not induce a consistent pattern of change in the proliferation and apoptotic indices of individual tumours, but there is a tendency to reduce proliferative activity over all the tumours as a group. It was also found that chemotherapy is capable of modifying the expression of the oncoproteins c-erbB-2 and p53 in a minority of cases of breast cancer, usually resulting in an acquisition of immunoreactive oncoprotein. It is important to be aware of these effects when studying breast carcinomas removed after chemotherapy.

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Section: Changes In Oncoprotein Expression After Chemotherapymentioning

confidence: 59%

The effects of chemotherapy on morphology, cellular proliferation, apoptosis and oncoprotein expression in primary breast carcinoma

Rasbridge

Gillett²,

Seymour³

et al. 1994

Br J Cancer

138

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“…Overexpression of the c-erbB-2 proto-oncogene is associated with a high proliferative drive, occurring in 75-100% of comedo DCIS lesions but only 0-7% of non-comedo lesions ( Van de Vijver et al, 1988;Barnes et al, 1991). We have previously shown that comedo DCIS is hormone independent and does not require oestrogen to maintain its high proliferative rate (Holland et al, 1997).…”

Section: Apoptotic and Proliferative Indicesmentioning

confidence: 90%

Evidence of significant apoptosis in poorly differentiated ductal carcinoma in situ of the breast

Gandhi¹,

Pa²,

Knox³

et al. 1998

Br J Cancer

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Summary Following breast-conserving surgery for ductal carcinoma in situ (DCIS), the presence of comedo necrosis reportedly predicts for higher rates of post-operative recurrence. To examine the role of programmed cell death (apoptosis) in the aetiology of the cell death described as comedo necrosis, we studied 58 DCIS samples, using light microscopy, for morphological evidence of apoptotic cell death. The percentage of apoptotic cells (apoptotic index, Al) was compared between DCIS with and without evidence of 'comedo necrosis' and related to the immunohistochemical expression of the anti-apoptosis gene bcl-2, mitotic index (Ml), the cellular proliferation antigen Ki67, nuclear grade and oestrogen receptor (ER) status. Al was significantly higher in DCIS samples displaying high-grade comedo necrosis than in lowgrade non-comedo samples: median Al = 1.60% (range 0.84-2.89%) and 0.45% (0.1-1.31%) respectively (P < 0.001). Increasing nuclear grade correlated positively with Al (P < 0.001) and negatively with bcl-2 expression (P = 0.003). Bcl-2 correlated negatively with Al (P = 0.019) and strongly with ER immunoreactivity (P < 0.001). Cellular proliferation markers (Ml and Ki67 immunostaining) correlated strongly with Al and were higher in comedo lesions and tumours of high nuclear grade (P < 0.001 in all cases). Thus, apoptosis contributes significantly to the cell death described in ER-negative, high-grade DCIS in which a high proliferative rate is associated with a high apoptotic rate. It is likely that dysregulation of proliferation/apoptosis control mechanisms accounts for the more malignant features typical of ER negative comedo DCIS.

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“…Overexpression has not been observed in TDLUs (De Potter et al 1989, Allred et al 1992) and it has been detected only rarely in ADH (Gusterson et al 1988, De Potter et al 1989, Lodato et al 1990, Allred et al 1992. Many studies have evaluated erbB-2 in DCIS (van de Vijer et al 1988, Bartkova et al 1990, Lodato et al 1990, Ramachandra et al 1990, Barnes et al 1991, Walker et al 1991, Allred et al 1992, Barnes et al 1992a, Schimmelpenning et al 1992, Somerville et al 1992, De Potter et al 1993, 1995, Tsuda et al 1993, Bobrow et al 1994, Poller et al 1994, Zafrani et al 1994, Leal et al 1995, Albonico et al 1996, Berardo et al 1996a. The average incidence of amplification and/or overexpression was about 10% in non-comedo compared with 60% in comedo lesions.…”

Section: Oncogenes and Tumor Suppressor Genes In Premalignant Breast mentioning

confidence: 99%

Histological and biological evolution of human premalignant breast disease.

Allred

Mohsin²,

Fuqua³

2001

Endocrine-Related Cancer

353

242

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Most human invasive breast cancers (IBCs) appear to develop over long periods of time from certain pre-existing benign lesions. Of the many types of benign lesions in the human breast, only a few appear to have significant premalignant potential. The best characterized of these include atypical hyperplasias and in situ carcinomas and both categories are probably well on along the evolutionary pathway to IBC. Very little is known about earlier premalignant alterations. All types of premalignant breast lesions are relatively common but only a small proportion appear to progress to IBC. They are currently defined by their histological features and their prognosis is imprecisely estimated from indirect epidemiological evidence. Although lesions within specific categories look alike, they must possess underlying biological differences causing some to remain stable and others to progress. Recent studies suggest that they evolve by highly diverse genetic mechanisms and research into these altered pathways may identify specific early defects that can be targeted to prevent premalignant lesions from developing or becoming cancerous. It is far more rational to think that breast cancer can be prevented than cured once it has developed fully. This review discusses histological models of human premalignant breast disease that provide the framework for scientific investigations into the biological alterations behind them and examples of specific biological alterations that appear to be particularly important.

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Relationship between c-erbB-2 immunoreactivity and thymidine labelling index in breast carcinomain situ

Cited by 57 publications

References 22 publications

The effects of chemotherapy on morphology, cellular proliferation, apoptosis and oncoprotein expression in primary breast carcinoma

The effects of chemotherapy on morphology, cellular proliferation, apoptosis and oncoprotein expression in primary breast carcinoma

Evidence of significant apoptosis in poorly differentiated ductal carcinoma in situ of the breast

Histological and biological evolution of human premalignant breast disease.

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