The potential role for prolactin-inducible protein (PIP) as a marker of human breast cancer micrometastasis

Clark, Jackson; Snell, Linda; Shiu, Robert P. C.; Orr, F. W.; Maitre, Nathalie L.; Vary, Calvin P.H.; Cole, David J.; Watson, Peter H.

doi:10.1038/sj.bjc.6690799

Cited by 57 publications

(47 citation statements)

References 33 publications

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“…This result is in agreement with the observation of high ChA serum level in small-sized (Ͻ2 cm) but intensely ChAimmunoreactive NE tumors (27). In addition, a potential role of GCDFP-15 as a marker of breast cancer micrometastasis has been recently proposed (28). Thus, the possibility of using Chs or GCDFP-15 serum values in the follow-up of these patients can justify the immunophenotyping of the tumors.…”

Section: Discussionsupporting

confidence: 76%

Expression of Apocrine Differentiation Markers in Neuroendocrine Breast Carcinomas of Aged Women

et al. 2001

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Neuroendocrine (NE) breast carcinomas are a rare entity in young women; however, their frequency increases in aged patients. The present work demonstrates that NE breast carcinomas in elderly women can also express an apocrine immunophenotype and analyzes the histological and clinical aspects of such differentiation. A selected series of 50 NE tumors (positive for NE markers in >50% of the cells) was tested for the immunocytochemical expression of gross cystic disease fluid protein-15 (GCDFP-15). The results demonstrated that about 50% of moderately (G2) and well-differentiated (G1) NE breast carcinomas (mucinous, solid papillary, and solid cohesive histotypes) coexpressed the apocrine marker. In these cases, specific mRNA for GCDFP-15 (PIP) and for chromogranin A (ChA) was demonstrated using in situ hybridization (ISH). Carcinomas of the alveolar subtype (G2) and poorly differentiated carcinomas (G3), including one case of atypical carcinoid, were pure NE carcinomas, devoid of apocrine differentiation. The steroid receptor status of these lesions was evaluated to test a possible involvement of androgen receptors in apocrine differentiation. We demonstrated that the level of AR and the mean age of patients at diagnosis were significantly higher in apocrine than in nonapocrine differentiated tumors. The histological grade and the expression of estrogen receptor (ER) significantly influenced the prognosis of these NE carcinomas, either pure or NE-apocrine differentiated. The most original result of our study is therefore the demonstration of a possible divergent apocrine differentiation of NE breast carcinomas that might be regulated by the activation of androgen receptors in elder patients. In addition, the possibility for using Chs or GCDFP-15 serum values in the follow-up of these patients, as demonstrated in two cases of the present series, can justify the immunophenotyping of the tumors.

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Section: Discussionsupporting

confidence: 76%

Expression of Apocrine Differentiation Markers in Neuroendocrine Breast Carcinomas of Aged Women

et al. 2001

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“…PIP expression levels are correlated with ESR1 and PGR positive status. 15,16 MGP belongs to the osteocalcin/matrix gla-protein family that associates with the organic matrix of bone and cartilage and is thought to act as an inhibitor of bone formation. 17…”

Section: Genes Co-clustering With Esr1mentioning

confidence: 99%

Genes that co-cluster with estrogen receptor alpha in microarray analysis of breast biopsies

et al. 2001

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The estrogen receptor plays a critical role in the pathogenesis and clinical behavior of breast cancer. To better understand the molecular basis of estrogen-dependent forms of this disease we studied gene expression profiles from 53 primary breast cancer biopsies. Gene expression data for more than 7000 genes were generated from each tumor sample with oligo microarrays. A standard correlation-clustering algorithm identified 18 genes that co-clustered with estrogen receptor alpha. Eleven of these genes had previously been associated with estrogen regulation or breast tumorigenesis including trefoil factor 1 and estrogen regulated LIV-1. Additional study of these 18 genes may further delineate the role of estrogen receptor in breast cancer, generate new predictive biomarkers for response to endocrine therapies and identify novel therapeutic targets. The Pharmacogenomics Journal ( BACKGROUNDThe estrogen receptor is a ligand-activated transcription factor containing hormone binding, DNA binding and transcription activation domains. 1 It is expressed in normal breast and 50-80% of breast cancers, depending on the assay used. 2-4 Estrogen receptor (ER) is a favorable prognostic factor and ER positive malignancies have a lower risk of relapse and a better overall survival. 5 However, ESR1 analysis is most useful in predicting response to endocrine therapies, although approximately half of all ER-positive cancers do not respond to antiestrogens or estrogen deprivation therapies. 6 The molecular basis for ESR1-positive, endocrine therapy-resistant disease is not well understood. Somatic mutations in ESR1 are rare, even in breast cancers that have acquired resistances to endocrine therapies. This finding has focused attention on other mechanisms, including the overexpression of tyrosone-kinase linked growth factor receptors, transcriptional coactivators such as AIB1 (amplified in breast cancer 1) or cell cycle regulators including Cyclin D1. Additional possibilities include mutations in other genes involved in the regulation of estrogen-dependent growth.Expression of the estrogen-regulated genes, progesterone receptor (PGR) and trefoil factor 1 (TFF1 or PS2) indicate the presence of a functional and activated ER. 7 Both of these proteins are predictive biomarkers for breast cancer endocrine therapy, although less valuable than ER in distinguishing estrogen-dependent from estrogen-independent breast cancer. The use of PGR improves upon the predictive value of ER alone, yet ෂ 40% of tumors that express both ER and PGR fail to respond to endocrine treatments in the metastatic setting. 8 Similarly, TFF1 is associated with a good prognosis and predicts a positive response to hormonal therapy, but it has not proved to be sufficient as a predictive biomarker for routine evaluation of breast cancer. 9 Thus, PGR and TFF1 may be modestly useful

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“…The final method of analysis is a multiple marker real-time RT -PCR assay. The PCR assay was developed to detect cytokeratin 19 (CK19), mammaglobin and prolactin-inducible peptide (PIP) (Clark et al, 1999), which are expressed in breast epithelial cells but at low levels in normal blood components. CK19 was chosen as it is expressed in the majority of breast cancers (Bartek et al, 1986;Moll, 1994), and has been extensively used in studies in this area (Slade et al, 1999;Smith et al, 2000;Aerts et al, 2001;Stathopoulou et al, 2002Stathopoulou et al, , 2003.…”

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confidence: 99%

Detection of circulating epithelial cells in the blood of patients with breast cancer: comparison of three techniques

et al. 2005

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This study compares the sensitivities and specificities of three techniques for the detection of circulating epithelial cells in the blood of patients with breast cancer. The number of circulating epithelial cells present in the blood of 40 patients with metastatic breast cancer and 20 healthy volunteers was determined by: immunomagnetic separation (IMS) and laser scanning cytometry (LSC), cell filtration and LSC and a multimarker real-time RT -PCR assay. Numbers of cytokeratin-positive cells identified and expression of three PCR markers were significantly higher in the blood of patients with breast cancer than in healthy volunteers. Using the upper 95% confidence interval of cells detected in controls to determine positive patient samples: 30% of patients with metastatic breast cancer were positive following cell filtration, 48% following IMS, and 60, 45 and 35% using real-time RT -PCR for cytokeratin 19, mammaglobin and prolactin-inducible peptide. Samples were significantly more likely to be positive for at least one PCR marker than by cell filtration (83 vs 30%, Po0.001) or IMS (83 vs 48%, Po0.001).The use of a multimarker real-time RT -PCR assay was therefore found to be the most sensitive technique for the detection of circulating epithelial cells in the blood of patients with breast cancer.

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The potential role for prolactin-inducible protein (PIP) as a marker of human breast cancer micrometastasis

Cited by 57 publications

References 33 publications

Expression of Apocrine Differentiation Markers in Neuroendocrine Breast Carcinomas of Aged Women

Expression of Apocrine Differentiation Markers in Neuroendocrine Breast Carcinomas of Aged Women

Genes that co-cluster with estrogen receptor alpha in microarray analysis of breast biopsies

Detection of circulating epithelial cells in the blood of patients with breast cancer: comparison of three techniques

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