Pattern of expression of c-erbB-2 oncoprotein in human fetuses

Quirke, Philip; Pickles, A.R.; Tuzi, NL; Mohamdee, O; Gullick, WJ

doi:10.1038/bjc.1989.221

Cited by 62 publications

(25 citation statements)

References 30 publications

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“…This is probably because HER2 expression plays an important role in embryogenesis. HER2 is expressed in lung, skin, gut, muscle, and neural tissue and plays an important role in mesenchymal-epithelial communication [16, 17]. It also plays an important role in heart development and function [18].…”

Section: Discussionmentioning

confidence: 99%

Clinical Characteristics and Prognosis of Pregnancy-Associated Breast Cancer: Poor Survival of Luminal B Subtype

Bae

Jung

et al. 2018

Oncology

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Background: Pregnancy-associated breast cancer (PABC) is rare and is generally defined as breast cancer diagnosed during pregnancy or within 1 year of delivery. The average ages of marriage and childbearing are increasing, and PABC is expected to also increase. This study is intended to increase understanding of the characteristics of PABC. Methods: A database of 2,810 patients with breast cancer diagnosed when they were less than 40 years of age was reviewed. The clinicopathological factors and survival of PABC (40 patients) were compared to those of patients with young breast cancer (YBC, non-pregnant or over 12 months after delivery; 2,770 patients). Results: PABC had significantly lower estrogen receptor (ER) and progesterone receptor (PR) expression (ER-positive 50.0%, PR-positive 45.0%) and higher HER2 overexpression (38.5%) than YBC. The most common subtype of PABC was triple-negative breast cancer (TNBC; 35.9%), and luminal A subtype represented only 7.7% of cases. In univariate analysis, PABC had significantly worse disease-free survival (DFS) and breast cancer-specific survival (BCSS) compared to YBC. In multivariate analysis, PABC was associated with worse BCSS (HR 4.0, 95% CI 1.2–12.9, p = 0.019) and survival, but there was no difference in DFS between PABC and YBC. In subgroup analysis by subtype, luminal B subtype of PABC showed worse DFS (HR 3.5; 95% CI 1.1–11.2, p = 0.039) and BCSS (HR 10.2, 95% CI 1.2–87.1, p = 0.035), especially with high Ki67. However, no differences were demonstrated in other subtypes. Conclusion: In this study, PABC showed lower expression of ER/PR, higher overexpression of HER2, fewer luminal A subtype, and more TNBC subtype compared to YBC. PABC had worse BCSS, especially luminal B subtype, compared to YBC.

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Section: Discussionmentioning

confidence: 99%

Clinical Characteristics and Prognosis of Pregnancy-Associated Breast Cancer: Poor Survival of Luminal B Subtype

Bae

Jung

et al. 2018

Oncology

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“…c-erbB-2 is an oncogene normally expressed during embryonic lung/development, reaching a maximum at 8 to 10 weeks, and by 12 weeks only the bronchial epithelium is stained (Quirke et al, 1989). The tracheo-bronchial tree is completely developed by the 16th week in human foetuses (Reid, 1967).…”

Section: Discussionmentioning

confidence: 99%

Potential role ofbcl-2 as a suppressor of tumour angiogenesis in non-small-cell lung cancer

et al. 1997

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It has been reported that genes regulating apoptosis may play a role in tumoral angiogenesis. This study examined the relationship between tumour vascularization, a measure of tumour angiogenesis, and bcl‐2 and p53 expression in operable non‐small‐cell lung cancer (NSCLC). The relationship between bcl‐2, p53 and tumour vascularization and epidermal‐growth‐factor‐receptor(EGFR) and c‐erbB‐2 expression was also studied. Tissue sections from resected tumour specimens of 107 NSCLC patients were evaluated immunohistochemically for vascular grade and bcl‐2, p53, EGFR and c‐erbB‐2 expression. bcl‐2 expression was found in 20/107 (19%) cases and was associated with squamous‐cell histology (p = 0.03). A strong inverse relationship was found between bcl‐2 expression and vascular grade (p = 0.005). All c‐erbB‐2‐positive cases were negative for bcl‐2 expression (p = 0.01). Overall no association was found between c‐erbB‐2 expression and vascular grade. However, in bcl‐2‐negative cases positive c‐erbB‐2 expression correlated with low angiogenesis (p = 0.05). No relationship was found between p53 and EGFR expression and bcl‐2, c‐erbB‐2 or vascular grade. The improved prognosis reported in bcl‐2‐positive NSCLC may be related to low tumour vascularization. The results suggest that the anti‐apoptotic gene bcl‐2 plays a role in regulating tumour angiogenesis. Since normal lung epithelium expresses bcl‐2, a sequence of tumour progression involving loss of bcl‐2, then activation of c‐erbB‐2 or increase in tumour vascularization is proposed. Int. J. Cancer 74:565–570, 1997.© 1997 Wiley‐Liss, Inc.

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“…This poor prognostic effect was observed throughout the period of follow-up, and these findings are similar to those observed in other studies (Slamon et 8 10 12 al., 1989;Wright et al, 1989a;Lovekin et al, 1989 Il ------------1... n phenotype in breast cancer. This ligand may be a novel growth factor which, after binding, modifies the response of cells expressing the receptor to such factors as tumour necrosis factor (Hudziack et al, 1989) or part of a cell-cell signalling apparatus (Gusterson et al, 1988;Quirke et al, 1989). …”

Section: Tumour Sizementioning

confidence: 99%

The long term prognostic significance of c-erbB-2 in primary breast cancer

Winstanley

Cooke²,

Murray³

et al. 1991

Br J Cancer

204

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SummaryThe expression of the c-erbB-2 oncogene has been evaluated using an immunohistochemical technique with the 21N polyclonal antibody in paraffin embedded tissue from 465 patients treated between the years [1975][1976][1977][1978][1979][1980][1981] for Stage I and II breast cancer. One hundred and four (22%) patients exhibited positive staining. This was not associated with any other variables. Expression of the oncogene was associated with significantly poorer survival which was independent of other tumour variables.The proto-oncogene c-erbB-2 encodes a protein present at the cell surface which has considerable homology with the epidermal growth factor receptor EGFR (Coussens et al., 1985). Although originally identified as an oncogene in chemically induced neuroblastomas in rats (Pahdy et al., 1982;Bargmann et al., 1986), recent interest has focused on its role in human breast cancer. Studies on cell lines derived from human mammary carcinomas have demonstrated that c-erbB -2 can be overexpressed by several mechanisms including gene amplification (Kraus et al., 1987) and this is present in up to 30% of human breast cancers (Slamon et al., 1987;van de Vijver et al., 1987;Varley et al., 1987;Zhou et al., 1987).The development of both polyclonal and monoclonal antibodies to the oncoprotein has allowed its distribution to be evaluated in histological sections, and its presence and clinical significance to be correlated with amplification of its gene and expression of its mRNA (Venter et al., 1987;van de Vijver et al., 1987;Slamon et al., 1989;Gusterson et al., 1988). These studies have confirmed that both gene amplification and increased transcription of its mRNA are associated with expression of this putative receptor at the cell surface in patients with breast cancer. One study though has reported that 20% of patients expressing this receptor failed to exhibit a corresponding amplification of its gene (Berger et al., 1988) and has concluded that other mechanisms may also be of importance in allowing it to be expressed.In both molecular studies and those based on immunological detection of the protein expression of the receptor has been associated with the spread of tumour to the axillary lymph nodes, to the number of nodes involved (Zhou et al., 1987;Slamon et al., 1987Slamon et al., , 1989, larger tumours (van de Vijver et al., 1987) and with poor histological grade (Berger et al., 1988). However, the number of patients assessed in these studies is variable and some have contained too few patients to evaluate the statistical significance of the data. Reports of its clinical significance have been conflicting, with some investigators noting a poorer prognosis in patients expressing the protein (Slamon et al., 1989;Wright et al., 1989a; Lovekin et al., 1989) and others reporting little difference (Barnes et al., 1988;Zhou et al., 1989; Alli et al., 1988;Gusterson et al., 1988 obtained. In addition, blocks were obtained from 100 patients with both benign fibrocystic disease and fibroadenomas who had undergon...

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Pattern of expression of c-erbB-2 oncoprotein in human fetuses

Cited by 62 publications

References 30 publications

Clinical Characteristics and Prognosis of Pregnancy-Associated Breast Cancer: Poor Survival of Luminal B Subtype

Clinical Characteristics and Prognosis of Pregnancy-Associated Breast Cancer: Poor Survival of Luminal B Subtype

Potential role ofbcl-2 as a suppressor of tumour angiogenesis in non-small-cell lung cancer

The long term prognostic significance of c-erbB-2 in primary breast cancer

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