Immunodetectable cyclin D1is associated with oestrogen receptor but not Ki67 in normal, cancerous and precancerous breast lesions

Shoker, Balvinder; Jarvis, Christine; Davies, Michael; Iqbal, Mussawar; Sibson, D. Ross; Sloane, J P

doi:10.1054/bjoc.2001.1705

Cited by 52 publications

(41 citation statements)

References 15 publications

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“…Recent studies show that cyclin D1 is correlated strongly with ER and PR. [23][24][25][26][27] We also found that there was a strong, positive association between hormone receptors and cyclin D1 (P Ͻ 0.001).…”

Section: 7-9supporting

confidence: 56%

“…21,29 Many biologic variables commonly are associated and coexpressed in breast carcinoma. Cyclin D1 expression, as discussed earlier, has been associated closely with ER and PR status, [23][24][25][26][27] and functional interaction between cyclin D1 and ER is regulated by a signal-transduction pathway that involves the second messenger, cyclic AMP. 25 Altered p53 expression has been associated with negative ER status in many series.…”

Section: 30mentioning

confidence: 78%

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A comparison of five immunohistochemical biomarkers and HER‐2/neu gene amplification by fluorescence in situ hybridization in white and Korean patients with early‐onset breast carcinoma

Choi

Shin

Lee

et al. 2003

Cancer

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BACKGROUNDThe objective of this article was to compare five tumor markers between white women in the U.S. and native Korean women with early‐onset breast carcinoma.METHODSSixty Korean women who were diagnosed with breast carcinoma at age 45 years or younger and 60 white women with breast carcinoma who were matched by age were selected for this study. The median age of both groups was 37 years. Paraffin embedded blocks of the primary tumor were processed for immunohistochemical staining of estrogen receptor (ER), progesterone receptor (PR), p53, cyclin D1, and HER‐2/neu.RESULTSThe proportion of tumors that stained positive for ER, PR, p53, and cyclin D1 in the Korean women were 47.5%, 42.4%, 28.8%, and 40.9%, respectively; in the white women, the proportions were 43.9%, 52.6%, 21.1%, and 59.1%, respectively. The differences between the white patients and the Korean patients were not statistically significant with respect to any of those variables. A significant difference was found in the expression of HER‐2/neu. Specifically, positive HER‐2/neu status was observed in 47.5% of Korean women, compared with overexpression in only 15.8% of white women (P < 0.001). Fluorescence in situ hybridization analysis for HER‐2/neu gene amplification on all HER‐2/neu positive samples that scored 2 + and 3 + demonstrated a significant difference (P = 0.007) in gene amplification between the two populations. Differences in HER‐2/neu positivity were observed for the entire cohort as well as among the subsets of patients with negative and positive lymph node status. No association was found between immunoreactivity for the five markers and axillary lymph node metastasis.CONCLUSIONSThe findings of high positivity of HER‐2/neu expression and gene amplification in Korean women with early‐onset breast carcinoma may have potential implications for local and systemic management of breast carcinoma, especially anti‐HER‐2/neu therapy for patients with hormone receptor negativity. Further research will be needed to identify biologic and genetic factors and their effects on the survival between different racial groups. Cancer 2003. © 2003 American Cancer Society.DOI 10.1002/cncr.11703

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Section: 7-9supporting

confidence: 56%

Section: 30mentioning

confidence: 78%

A comparison of five immunohistochemical biomarkers and HER‐2/neu gene amplification by fluorescence in situ hybridization in white and Korean patients with early‐onset breast carcinoma

Choi

Shin

Lee

et al. 2003

Cancer

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“…Actually, increased cyclin D1 levels did not always correlate with increased proliferation as measured by in situ staining for Ki67 of breast cancers (Oyama et al, 1998;Shoker et al, 2001). Accordingly, cyclin D1 transgenic mice showed almost no alterations in their proliferation capacity.…”

Section: Cyclin D1 Overexpression Alters Proliferationmentioning

confidence: 99%

Gain of 11q/cyclin D1 overexpression is an essential early step in skin cancer development and causes abnormal tissue organization and differentiation

Burnworth¹,

Popp²,

Stark³

et al. 2006

Oncogene

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Non-melanoma skin cancers, in particular keratoacanthomas (KAs) and squamous cell carcinomas (SCCs), have become highly frequent tumor types especially in immunesuppressed transplant patients. Nevertheless, little is known about essential genetic changes. As a paradigm of 'early' changes, that is, changes still compatible with tumor regression, we studied KAs by comparative genomic hybridization and show that gain of chromosome 11q is not only one of the most frequent aberration (8/18), but in four tumors also the only aberration. Furthermore, 11q gain correlated with amplification of the cyclin D1 locus (10/14), as determined by fluorescence in situ hybridization, and overexpression of cyclin D1 protein (25/31), as detected by immunohistochemistry. For unraveling the functional consequence, we overexpressed cyclin D1 in HaCaT skin keratinocytes. These cells only gained little growth advantage in conventional and in organotypic cocultures. However, although the control vector-transfected cells formed a well-stratified and orderly differentiated epidermis-like epithelium, they showed deregulation of tissue architecture with an altered localization of proliferation and impaired differentiation. The most severe phenotype was seen in a clone that additionally upregulated cdk4 and p21. These cells lacked terminal differentiation, exhibited a more autonomous growth in vitro and in vivo and even formed tumors in two injection sites with a growth pattern resembling that of human KAs. Thus, our results identify 11q13 gain/cyclin D1 overexpression as an important step in KA formation and point to a function that exceeds its known role in proliferation by disrupting tissue organization and thereby allowing abnormal growth.

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“…The cyclin D1 protein is overexpressed in 30-50% of human breast cancers and the gene is amplified in approximately 15% of breast cancers (Sutherland and Musgrove, 2004). Cyclin D1 and estrogen receptor a (ERa) are frequently co-expressed in human ductal hyperplasia and breast cancer (Shoker et al, 2001). Moreover, cyclin D1 expression positively correlates with ERa expression in ductal carcinoma in situ (DCIS) (Oh et al, 2001).…”

Section: Introductionmentioning

confidence: 99%

Loss of cyclin D1 in concert with deregulated estrogen receptor α expression induces DNA damage response activation and interrupts mammary gland morphogenesis

et al. 2007

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We have previously shown that increased and deregulated estrogen receptor a expression in the mammary gland leads to the development of proliferative disease and cancer. To address the importance of cyclin D1 in ERa-mediated mammary tumorigenesis, we crossed ERa-overexpressing mice with cyclin D1 knockout mice. Mammary gland morphogenesis was completely interrupted in the ERa-overexpressing cyclin D1-deficient triple transgenic mice. In addition to a highly significant reduction in mammary epithelial cell proliferation, cyclin E was upregulated resulting in DNA damage checkpoint activation and apoptosis. This imbalance between proliferative and apoptotic rates in conjunction with remarkable structural defects and cellular disorganization in the terminal end buds interrupted ductal morphogenesis. Interestingly, the structure of the mammary fat pad was fundamentally altered by the consequences of overexpressing ERa in the epithelial cells in the absence of cyclin D1 illustrating how alterations in the epithelial compartment can impact surrounding stromal composition. Transplantation of embryonic ERa-overexpressing and cyclin D1-deficient mammary epithelium into the cleared fat pad of wild-type mice did not rescue the aberrant mammary gland phenotype indicating that it was intrinsic to the mammary epithelial cells. In conclusion, although cyclin D1 is not essential for proliferation of normal mammary epithelial cells, ERa-overexpressing cells are absolutely dependent on cyclin D1 for proliferation. This differential requirement for cyclin D1 in normal vs abnormal mammary epithelial cells supports the application of cyclin D1 inhibitors as therapeutic interventions in ERa-overexpressing breast cancers.

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Immunodetectable cyclin D1is associated with oestrogen receptor but not Ki67 in normal, cancerous and precancerous breast lesions

Cited by 52 publications

References 15 publications

A comparison of five immunohistochemical biomarkers and HER‐2/neu gene amplification by fluorescence in situ hybridization in white and Korean patients with early‐onset breast carcinoma

A comparison of five immunohistochemical biomarkers and HER‐2/neu gene amplification by fluorescence in situ hybridization in white and Korean patients with early‐onset breast carcinoma

Gain of 11q/cyclin D1 overexpression is an essential early step in skin cancer development and causes abnormal tissue organization and differentiation

Loss of cyclin D1 in concert with deregulated estrogen receptor α expression induces DNA damage response activation and interrupts mammary gland morphogenesis

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