Organotropism and prognostic marker discordance in distant metastases of breast carcinoma: fact or fiction? A clinicopathologic analysis

Romain, P.; Madan, Rashna; Tawfik, Ossama; Damjanov, Ivan; Fan, Fang

doi:10.1016/j.humpath.2011.05.009

Cited by 29 publications

(16 citation statements)

References 20 publications

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“…The rate of ER À metastatic breast carcinomas is reported to be in the range of 40% to 52%. [55][56][57][58][59][60][61][62] In addition, ER is not entirely specific for breast primary tumors; it is also positive in most endometrial carcinomas, endocervical ADCs, and ovarian epithelial carcinomas and is infrequently positive in the lung or other primaries. For many years, ER, GCDFP-15, and MGB have been considered breast-specific immunomarkers in the workup of tumors of uncertain origin.…”

Section: Review Of Selected Antibodiesmentioning

confidence: 99%

Immunohistochemistry in Undifferentiated Neoplasm/Tumor of Uncertain Origin

Lin

Liu

2014

Archives of Pathology &Amp; Laboratory Medicine

108

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Context Immunohistochemistry has become an indispensable ancillary study in the identification and classification of undifferentiated neoplasms/tumors of uncertain origin. The diagnostic accuracy has significantly improved because of the continuous discoveries of tissue-specific biomarkers and the development of effective immunohistochemical panels. Objectives To identify and classify undifferentiated neoplasms/tumors of uncertain origin by immunohistochemistry. Data Sources Literature review and authors' research data and personal practice experience were used. Conclusions To better guide therapeutic decisions and predict prognostic outcomes, it is crucial to differentiate the specific lineage of an undifferentiated neoplasm. Application of appropriate immunohistochemical panels enables the accurate classification of most undifferentiated neoplasms. Knowing the utilities and pitfalls of each tissue-specific biomarker is essential for avoiding potential diagnostic errors because an absolutely tissue-specific biomarker is exceptionally rare. We review frequently used tissue-specific biomarkers, provide effective panels, and recommend diagnostic algorithms as a standard approach to undifferentiated neoplasms.

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Section: Review Of Selected Antibodiesmentioning

confidence: 99%

Immunohistochemistry in Undifferentiated Neoplasm/Tumor of Uncertain Origin

Lin

Liu

2014

Archives of Pathology &Amp; Laboratory Medicine

108

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“…Hence, the variation of ER/PR and/or HER2 statuses of tumors during the metastatic process may help oncologists to change treatment plans. Although most scientiWc literature reported a stability of HER2 status between primary tumors and visceral metastatic lesions (Fabi et al 2011;Jensen et al 2011;Masood and Bui 2000;Niehans et al 1993;Tapia et al 2007;Vincent-Salomon et al 2002;Vincent-Salomon et al 2007), other papers showed a high discrepancy rate (>15%) between HER2 expression in primary compared to metastases of breast cancer (Pusztai et al 2010;St Romain et al 2011) (publications summarized in Table 5); it is still unclear whether ER/PR and HER2 statuses diVer in visceral metastases compared with primary tumors in breast cancer patients with or without treatment.…”

Section: Discussionmentioning

confidence: 99%

Comparison of ER/PR and HER2 statuses in primary and paired liver metastatic sites of breast carcinoma in patients with or without treatment

Liu

Deng

Jia

et al. 2012

J Cancer Res Clin Oncol

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“…For example, breast tumours that spread to the brain tend to be associated with high grade IC NST of HER2 or basal-like subtypes; metastases occur relatively quickly, with a latency of less than 5 years (Lagerwaard et al, 1999). Conversely, data accumulated here and from the literature (Bigorie et al, 2010, Demopoulos et al, 1987, Ferlicot et al, 2004, Borst and Ingold, 1993, St Romain et al, 2012 suggest metastasis to gynaecological organs is associated with different primary tumour characteristics and a different clinical pattern of progression to that seen for brain metastasis. Some of the key findings from this study and supporting literature are:…”

Section: Discussionmentioning

confidence: 87%

“…Small studies have found breast cancers that spread to gynaecological organs are predominantly ER positive and HER2 negative (Bigorie et al, 2010, St Romain et al, 2012) and as mentioned above invasive lobular carcinomas are more likely to spread to these sites, suggesting that hormonal signalling and/or a diffuse growth pattern might be important. In support of this, evidence from autopsy studies also…”

Section: Dcis Ductalmentioning

confidence: 92%

“…Furthermore evidence from autopsy studies show that gynaecological metastases from mixed ductal lobular carcinomas are frequently of the lobular type (Lamovec and Bracko, 1991). ILC that spread to the peritoneum, gastrointestinal tract and gynaecological organs were also E-cadherin negative (88%; (Ferlicot et al, 2004)) and predominately ER positive and HER2 negative (Bigorie et al, 2010, St Romain et al, 2012. This suggests a possible role for hormone regulation and E-cadherin dysfunction in this unique process (Lamovec and Bracko, 1991).…”

Section: Metastasis To Gynaecological Sitesmentioning

confidence: 99%

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Intratumour heterogeneity in the development and progression of breast cancer

Kutasovic¹

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The extent of intratumour heterogeneity and its clinical implications are poorly understood.This thesis addresses this theme of tumour heterogeneity with a broad focus on invasive lobular carcinomas of the breast. More specifically the focus will be on studying the various mechanisms of deregulation of E-cadherin, the morphological and phenotypic variation mixed ductal lobular carcinomas, and finally heterogeneity of metastatic progression.Invasive lobular carcinoma (ILC) is the second most common breast cancer subtype, accounting for 10-15% of the all breast cancers, and is the most common 'special type'.Biologically, the most distinguishing feature of ILC is the loss of the cellular adhesion molecule E-cadherin (absent in up to 90% of ILC), and this is considered fundamental to development of the characteristic infiltrative growth pattern. The deregulation of Ecadherin is not fully understood, and so this thesis aims to investigate the mechanisms of E-cadherin deregulation in tumourigenesis. Co-localised with E-cadherin at the cell membrane are a series of proteins (including ECT2, RacGAP1 and N-WASP) which regulate the actin cytoskeleton; the expression of these proteins was investigated using immunohistochemistry (IHC) of breast cancer tissue microarrays (Chapter 3). Differences in cytoplasmic expression and localisation of these molecules were found between different histological types and clinicopathological parameters that warrant further investigation. It remains unclear whether these molecules contribute to deregulating cell adhesion in vivo.Mixed ductal-lobular carcinomas (MDL) display both ductal and lobular morphology, and are a clear example of intratumour morphological heterogeneity. It is hypothesised that these different components evolve from a common ancestor and diverge following deregulation of the E-cadherin complex. To address this hypothesis, a cohort of 82 MDLs was studied for clinical, morphological and molecular features (Chapter 4). Key findings include: i) MDLs more frequently co-exist with ductal carcinoma in situ (DCIS) than lobular carcinoma in situ (LCIS); ii) the E-cadherin-catenin complex was often normal in the ductal component but deregulated in the lobular component; iii) E-cadherin deregulation was different to that seen in classic ILC, which are typically completely negative for this marker, not aberrant; iv) Epithelial to mesenchymal transition marker expression was not associated with E-cadherin deregulation. Exome sequencing was performed to investigate clonal relationships between the different intratumour morphologies, and identify iii mechanisms underlying the change from a 'ductal' to a more infiltrative 'lobular' growth pattern. Preliminary analysis revealed that i) all morphological components within a case are clonally related; ii) divergence of the morphological components may occur early during tumour evolution (where there are both DCIS and LCIS present) or later during tumour progression (cases with only DCIS detectible); and iii) mutations were identi...

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Organotropism and prognostic marker discordance in distant metastases of breast carcinoma: fact or fiction? A clinicopathologic analysis

Cited by 29 publications

References 20 publications

Immunohistochemistry in Undifferentiated Neoplasm/Tumor of Uncertain Origin

Immunohistochemistry in Undifferentiated Neoplasm/Tumor of Uncertain Origin

Comparison of ER/PR and HER2 statuses in primary and paired liver metastatic sites of breast carcinoma in patients with or without treatment

Intratumour heterogeneity in the development and progression of breast cancer

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