Distinct Genetic and Epigenetic Changes in Medullary Breast Cancer

Osin, Peter; Lu, Ye; Stone, Joanne; Crook, Tim; Houlston, Richard S.; Gasco, Milena; Gusterson, B A; Shipley, Janet

doi:10.1177/106689690301100301

Cited by 28 publications

(14 citation statements)

References 18 publications

(18 reference statements)

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“…It has been previously reported that medullary carcinomas have a high incidence of positivity for basal cell -like markers (43). We have also recently reported distinct genetic and epigenetic changes in medullary carcinoma, with chromosome copy number changes showing some similarities to BRCA1-associated tumors (44). Our results support the emerging data indicating that BRCA1-associated tumors and medullary carcinomas share morphologic and genetic similarities.…”

Section: Discussionsupporting

confidence: 81%

Annexin A8 Is Up-Regulated During Mouse Mammary Gland Involution and Predicts Poor Survival in Breast Cancer

Stein

Price

Morris

et al. 2005

Clinical Cancer Research

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Purpose: Microarray studies have linked Annexin A8 RNA expression to a ''basal cell^like'' subset of breast cancers, including BRCA1-related cancers, that are characterized by cytokeratin 5 (CK5) and CK17 expression and show poor prognosis. We assessed Annexin A8's contribution to the overall prognosis and its expression in normal, benign, and cancerous tissue and addressed Annexin A8's physiologic role in the mammary gland. Experimental Design: Using microarrays and reverse transcription-PCR, the Annexin A8 expression was studied during mouse mammary gland development and in isolated mammary structures. Reverse transcription-PCR on cultured human luminal and basal cells, along with immunocytochemistry on normal and benign breast tissues, was used for cellular localization. Annexin A8's prognostic relevance and its coexpression with CK5 were assessed on tissue arrays of 1,631cases of invasive breast cancer. Coexpression was further evaluated on a small cohort of 14 BRCA1-related breast cancers. Results: Annexin A8 was up-regulated during mouse mammary gland involution and in pubertal ductal epithelium. Annexin A8 showed preferred expression in cultured basal cells but predominant luminal expression in normal human breast tissue in vivo. Hyperplasias and in situ carcinomas showed a strong staining of basal cells. Annexin A8 expression was significantly associated with grade (P < 0.0001), CK5 (P < 0.0001), and estrogen receptor status (P < 0.0001); 85.7% BRCA1-related breast tumors coexpressed Annexin A8 and CK5. Conclusion: Annexin A8 is involved in mouse mammary gland involution. In humans, it is a luminally expressed protein with basal expression in cell culture and in hyperplasia/ductal carcinoma in situ. Expression in invasive breast carcinomas has a significant effect on survival (P = 0.03) but is not independent of grade or CK5.

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Section: Discussionsupporting

confidence: 81%

Annexin A8 Is Up-Regulated During Mouse Mammary Gland Involution and Predicts Poor Survival in Breast Cancer

Stein

Price

Morris

et al. 2005

Clinical Cancer Research

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“…CGH and conventional cytogenetic studies have shown that there is some degree of variation in the pattern of genetic alterations between different histological types of invasive breast cancer [2,10,[35][36][37][38][39][40][41][42][43][44][45][46]. Although differences between histological subtypes do exist, this association is not as strong as it happens to be with grade [2,9,12].…”

Section: Invasive and In Situ Breast Carcinomasmentioning

confidence: 93%

Molecular evolution of breast cancer

Simpson

Reis‐Filho

Gale

et al. 2005

The Journal of Pathology

449

378

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Molecular analysis of invasive breast cancer and its precursors has furthered our understanding of breast cancer progression. In the past few years, new multi-step pathways of breast cancer progression have been delineated through genotypic-phenotypic correlations. Nuclear grade, more than any other pathological feature, is strongly associated with the number and pattern of molecular genetic abnormalities in breast cancer cells. Thus, there are two distinct major pathways to the evolution of low-and high-grade invasive carcinomas: whilst the former consistently show oestrogen receptor (ER) and progesterone receptor (PgR) positivity and 16q loss, the latter are usually ER/PgR-negative and show Her-2 overexpression/amplification and complex karyotypes. The boundaries between the evolutionary pathways of well-differentiated/low-grade ductal and lobular carcinomas have been blurred, with changes in E-cadherin expression being one of the few distinguishing features between the two. In addition, lesions long thought to be precursors of breast carcinomas, such as hyperplasia of usual type, are currently considered mere risk indicators, whilst columnar cell lesions are now implicated as non-obligate precursors of atypical ductal hyperplasia (ADH) and well-differentiated ductal carcinoma in situ (DCIS). However, only through the combination of comprehensive morphological analysis and cutting-edge molecular tools can this knowledge be translated into clinical practice and patient management.

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“…[90][91][92][93][94] This may be in part due to the presence of a dysfunctional BRCA1 pathway in these tumors. 32,82,83 BRCA1 gene promoter is methylated in 460% of medullary 95,96 and metaplastic 32 breast cancers of basal-like phenotype. Sporadic invasive ductal carcinomas with basal-like phenotype express ID4, a negative regulator of BRCA1, 97,98 at significantly higher levels than grade-matched controls.…”

Section: S Badve Et Almentioning

confidence: 99%

Basal-like and triple-negative breast cancers: a critical review with an emphasis on the implications for pathologists and oncologists

et al. 2011

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Breast cancer is a heterogeneous disease encompassing a variety of entities with distinct morphological features and clinical behaviors. Although morphology is often associated with the pattern of molecular aberrations in breast cancers, it is also clear that tumors of the same histological type show remarkably different clinical behavior. This is particularly true for 'basal-like cancer', which is an entity defined using gene expression analysis. The purpose of this article was to review the current state of knowledge of basal-like breast cancers, to discuss the relationship between basal-like and triple-negative breast cancers, and to clarify practical implications of these diagnoses for pathologists and oncologists.

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Distinct Genetic and Epigenetic Changes in Medullary Breast Cancer

Cited by 28 publications

References 18 publications

Annexin A8 Is Up-Regulated During Mouse Mammary Gland Involution and Predicts Poor Survival in Breast Cancer

Annexin A8 Is Up-Regulated During Mouse Mammary Gland Involution and Predicts Poor Survival in Breast Cancer

Molecular evolution of breast cancer

Basal-like and triple-negative breast cancers: a critical review with an emphasis on the implications for pathologists and oncologists

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