Amplification of Growth Regulatory Genes in Intraductal Breast Cancer Is Associated with Higher Nuclear Grade but Not with the Progression to Invasiveness

Glöckner, Sabine C.; Lehmann, Ulrich; Wilke, Nadine; Kleeberger, Wolfram; Kreipe, Hans

doi:10.1038/labinvest.3780265

Cited by 34 publications

(20 citation statements)

References 24 publications

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“…The higher MNA, therefore, can be expected to reflect the increased proliferation in Nigerian breast cancer. This view is further substantiated by the study of Glöckner (2001) who showed that the amplification and increased expression of erbB2 (growth factor receptor associated with increased growth rate) is associated with higher nuclear grade in intraductal cancers.…”

Section: Discussionmentioning

confidence: 57%

Nuclear Morphometry in African Breast Cancer

Ikpatt¹,

Kuopio

Collan³

2011

Image Anal Stereol

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Three hundred cases of invasive breast cancer diagnosed between 1983 and 1999 in Calabar, Nigeria were analysed to determine the nuclear morphometric variables, and evaluate the prognostic potential of nuclear morphometry in Nigerian breast cancers. The necessary follow-up was available for 129 patients. The nuclear area was the most valuable variable. In the Nigerian material, the mean nuclear area (MNA) (SD) was 89.2 (34.0) µm 2 . MNA was significantly higher in tumours of the postmenopausal than premenopausal (p = 0.0405), in LN+ than LN-(p = 0.0202) patients, and in tumours over 3 cm than smaller ones (p < 0.0001). There were also significant differences between different clinical stages, histological grades, and histological types of tumours. Significant correlations were observed between MNA and histological grade (r = 0.64), standard mitotic index (r = 0.45) and tumour size (r = 0.20). MNA as a continuous variable was a statistically significant prognosticator in the whole material (p = 0.0281), and among the postmenopausal patients (p = 0.0238). Univariate cox´s regression demonstrated one significant grading cutpoint at MNA = 111 µm 2 , which divided the material into two groups of different survival. The development of a morphometric grading system optimal for the Nigerian material could use the latter cut-point between nuclear scores 2 and 3 in the grading system. The earlier proven cut-point of 47 µm 2 could be used between nuclear scores 1 and 2.

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Section: Discussionmentioning

confidence: 57%

Nuclear Morphometry in African Breast Cancer

Ikpatt¹,

Kuopio

Collan³

2011

Image Anal Stereol

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“…PEG10 is activated in subsets of human breast and prostate carcinomas. A substantial subset of human breast carcinomas, including ductal carcinoma in situ, overexpress MYC either due to gene amplification or transcriptional deregulation (18)(19)(20). To ask whether the PEG10 gene is activated in primary human breast cancers, we carried out immunohistochemistry for PEG10 protein, using an affinity-purified polyclonal antiserum raised against a peptide epitope in the PEG10 major open reading frame (the RF1 protein isoform), in a series of 23 paraffin-embedded breast biopsies with standard histologic sections and in a second series of 161 breast cancer cases in a tissue array.…”

Section: Resultsmentioning

confidence: 99%

PEG10 Is a c-MYC Target Gene in Cancer Cells

Margolin

Salas

et al. 2006

Cancer Research

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The product of the imprinted gene paternally expressed gene-10 (PEG10) has been reported to support proliferation in hepatocellular carcinomas, but how this gene is regulated has been an open question. We find that MYC knockdown by RNA interference suppresses PEG10 expression in Panc1 pancreatic carcinoma and HepG2 hepatocellular carcinoma cells and that knockdown of PEG10 inhibits the proliferation of Panc1, HepG2, and Hep3B cells. Conversely, PEG10 was up-regulated by inducing c-MYC expression in a B-lymphocyte cell line. Chromatin immunoprecipitation from Panc1 cells showed c-MYC bound to an E-box-containing region in the PEG10 first intron and site-directed mutagenesis showed that the most proximal E-box is essential for promoter activity. In a mouse mammary tumor virus (MMTV)-MYC transgenic mouse model of breast cancer, most but not all of the mammary carcinomas had strongly increased Peg10 mRNA compared with normal mammary gland. By immunohistochemistry, normal human breast and prostate epithelium was negative for the major isoform [reading frame-1 (RF1)] of PEG10 protein, but this cytoplasmic protein was strongly expressed in a subset of breast carcinomas in situ and invasive ductal carcinomas (f30%) and in a similar percentage of prostate cancers. As in the mouse model, we found positive, but not absolute, correlations between PEG10 and c-MYC in tissue arrays containing 161 human breast cancers (P < 0.002) and 30 prostate cancers (P = 0.014). Immunostaining of human placenta showed PEG10 and c-MYC proteins coexpressed in proliferating cytotrophoblast and coordinately lost in postmitotic syncytiotrophoblast. These findings link cancer genetics and epigenetics by showing that a classic protooncogene, MYC, acts directly upstream of a proliferationpositive imprinted gene, PEG10. (Cancer Res 2006; 66(2): 665-72)

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“…Even in studies in which amplification was detected in DCIS, the percentage of positive samples was low. For example, when Myc amplification was scored by using PCR analysis, only 6% (5/78) 69 or 7% (3/41) 38 of the DCIS samples were found to be positive. In the latter case, 27% (11/41) of the DCIS samples overexpressed Myc detected by IHC.…”

Section: Myc In Normal Human Breast and Breast Cancermentioning

confidence: 99%