Cytokeratin expression in breast cancer: Phenotypic changes associated with disease progression

Brotherick, I.; Robson, C.N.; Browell, D.A.; Shenfine, J.; White, M.D.; Cunliffe, W.J.; Shenton, B.K.; Egan, M.; Webb, L.A.; Lunt, L.G.; Young, J.R.; Higgs, M.J.

doi:10.1002/(sici)1097-0320(19980801)32:4<301::aid-cyto7>3.0.co;2-k

Cited by 43 publications

(30 citation statements)

References 24 publications

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“…As erbB2 overexpression was not observed in all tumors and because short hairpin RNA-mediated knockdown of CUX1 had no effect on erbB2 expression (data not shown), we consider it likely that the increase in erbB2 expression was not induced by CUX1 but rather was caused by molecular events that are independent of CUX1. Interestingly, cytokeratin 18 expression was reduced in many solid carcinomas as reported previously (26,27).…”

Section: Resultssupporting

confidence: 78%

Mouse Mammary Tumor Virus p75 and p110 CUX1 Transgenic Mice Develop Mammary Tumors of Various Histologic Types

et al. 2009

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The p75 and p110 isoforms of the CUX1 homeodomain protein are overexpressed in breast tumors and cancer cell lines. To assess and compare the ability of these short CUX1 isoforms in driving mammary tumor development, we used site-specific transgenesis into the Hprt locus to generate transgenic mice expressing p75 or p110 CUX1 under the control of the mouse mammary tumor virus-long terminal repeat. We report that mammary tumors developed after a long latency period, and although various histopathologies were observed, the proportion of adenosquamous carcinomas was significantly higher in p75 CUX1 than in p110 CUX1 transgenic mice. Metastasis to the lung was observed in three p75 CUX1 transgenic mice. Comparisons between tumors and adjacent normal mammary glands revealed that transgenes were overexpressed in most but not all tumors, yet in all cases tested, CUX1 DNA binding was increased, suggesting that both higher expression and changes in post-translational modifications can contribute to stimulate transgene activity. Interestingly, higher expression of erbB2 mRNA was seen in most tumors, not only solid carcinomas but also adenosquamous carcinomas, whereas higher expression of various Wnt genes and activation of the B-catenin pathway was observed primarily in adenosquamous carcinomas. Activation of erbB2 expression appeared to represent a cooperating event that occurred independently of CUX1. In contrast, chromatin immunoprecipitation, short hairpin RNA-mediated knockdown, and reporter assays established that CUX1 is involved in the transcriptional regulation of several Wnt genes. Together, these results support the notion that oncogenic activity of CUX1 can facilitate the establishment of a Wnt/B-catenin autocrine loop. [Cancer Res 2009;69(18):7188-97]

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Section: Resultssupporting

confidence: 78%

Mouse Mammary Tumor Virus p75 and p110 CUX1 Transgenic Mice Develop Mammary Tumors of Various Histologic Types

et al. 2009

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“…40 Previous studies have found an inverse association between luminal cytokeratin expression (CK18) and tumor grade, recurrence rate and ER status. 41 The results of our study with decreased expression of luminal markers and increased expression of basal markers also correlates with poor prognostic features and behavior of ER-negative tumors. 42 E-cadherin is an important mediator of cell-to-cell interaction and has been reported to be aberrantly expressed or absent in most of the lobular cancers of breast.…”

Section: Estrogen Receptor-negative Breast Carcinomasmentioning

confidence: 56%

Estrogen receptor-negative breast carcinomas: a review of morphology and immunophenotypical analysis

et al. 2005

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Estrogen receptor (ER)-negative breast cancers are a group of tumors with poor prognosis and fewer cancer prevention and treatment strategies compared to ER-positive tumors. The aim of this study was to assess the morphological characteristics and immunohistochemical profile of ER-negative tumors and thus to understand the biological behavior and unique nature. In total, 291 consecutive ER-negative cases available from our primary breast cancer series were examined. Hematoxylin-and eosin-stained sections of all the cases were studied for several morphological parameters and their immunophenotype profile. These findings were correlated with patient and tumor characteristics and survival data. ER-negative tumors constituted 30% of the primary operable breast cancer series. The majority of tumors were grade 3 (94%) and the commonest histological types were ductal/no specific type (85%), and atypical medullary carcinoma (8%). High-grade comedo-type necrosis, lymphoid stroma, central necrosis/fibrosis and pushing margins were the most common morphological features. The presence of a pushing margin showed a significant relation to androgen receptor negativity, absence of epidermal growth factor receptor expression and negative lymph nodes. Lymphoid stroma and comedo-necrosis correlated with higher tumor grade. ER-negative breast cancers are a distinct group of tumors with several common morphological features. Grade 3 histology, pushing margin, lymphoid stroma, comedo-type necrosis and central fibrosis/necrosis are the dominant morphological findings. The presence of a pushing margin appears to have a significant correlation with negative lymph node status. ER-negative tumors show a higher expression of p53, CerbB2 and epidermal growth factor receptor compared to ER-positive breast cancer. These unique features support the concept that ER-negative tumors are a morphologically and phenotypically distinct entity and provide a rationale for the study and use of newer promising agents in the treatment of ER-negative breast cancer.

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“…It has been well demonstrated that breast cancer cells express fragments of cytokeratin-19 (Moll et al, 1982;Brotheric et al, 1998;Sheard et al, 2002), which is one of the various kinds of cytokeratins comprising the intermediate filaments of the cytoskeleton (Moll et al, 1982). Serum fragments of cytokeratin-19 can be detected using anti-CYFRA 21-1 antibody (Pujol et al, 1993).…”

Section: Discussionmentioning

confidence: 99%

Serum CYFRA 21-1 (cytokeratin-19 fragments) is a useful tumour marker for detecting disease relapse and assessing treatment efficacy in breast cancer

et al. 2004

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The usefulness of serum CYFRA 21-1 (cytokeratin-19 fragments) in monitoring the recurrence of breast cancer and in evaluating therapeutic effects was studied retrospectively. The sera from 173 patients with primary breast cancer or recurrent disease were measured for CYFRA 21-1, carcinoembryonic antigen (CEA), and carbohydrate antigen 15-3 (CA 15-3) levels. The positive rates of serum CYFRA 21-1 for stage IV (n ¼ 12) or recurrent disease (n ¼ 26) were 83.3 and 84.6%, respectively, while those of serum CEA were 41.7 and 26.9%, and those of serum CA 15-3 were 83.3 and 34.6%. The elevated preoperative levels of serum CYFRA 21-1 decreased to normal levels after curative operation, whereas the levels remained abnormally high after noncurative operation. There was a significantly high frequency of recurrence in patients with elevated levels of serum CYFRA 21-1 preoperatively compared to those with normal levels of the marker preoperatively. The serum CYFRA 21-1 levels were well correlated with response to chemotherapy. The positive rate of serum CYFRA 21-1 alone was higher than that of an assay combining CEA with CA 15-3, in both primary and recurrent cases (28.8 vs 18.8 and 84.6 vs 46.2%, respectively). These observations suggest that serum CYFRA 21-1 may be a reliable marker of recurrence or therapeutic efficacy.

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Cytokeratin expression in breast cancer: Phenotypic changes associated with disease progression

Cited by 43 publications

References 24 publications

Mouse Mammary Tumor Virus p75 and p110 CUX1 Transgenic Mice Develop Mammary Tumors of Various Histologic Types

Mouse Mammary Tumor Virus p75 and p110 CUX1 Transgenic Mice Develop Mammary Tumors of Various Histologic Types

Estrogen receptor-negative breast carcinomas: a review of morphology and immunophenotypical analysis

Serum CYFRA 21-1 (cytokeratin-19 fragments) is a useful tumour marker for detecting disease relapse and assessing treatment efficacy in breast cancer

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