Chromosomal aberrations as detected by array comparative genomic hybridization in early low-grade intraepithelial neoplasias of the breast

Stacher, Elvira; Boldt, Vivien; Leibl, Sebastian; Halbwedl, Iris; Popper, Helmut; Ullmann, Reinhard; Tavassoli, Fattaneh A.; Moinfar, Farid

doi:10.1111/j.1365-2559.2011.03918.x

Cited by 12 publications

(12 citation statements)

References 36 publications

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“…[22][23][24][25][26][27][28] Previously, Moinfar et al 22 analyzed loss of heterozygosity in Ductal Intraepithelial Neoplasiaflat lesions, and found significant alterations, including changes in common with concurrent carcinoma; however, 9 of the 22 studied cases were 'pleomorphic' Ductal Intraepithelial Neoplasia-flat, equivalent to clinging carcinoma (high nuclear grade flat ductal carcinoma in situ). In a subsequent study using array comparative genomic hybridization Moinfar's group showed by that Ductal Intraepithelial Neoplasia low grade harbored changes common to lobular neoplasia, low nuclear grade ductal carcinoma in situ, and invasive carcinoma (loss of 16q, gain of 1q).…”

Section: Pik3ca Mutations In Columnar Cell Lesionsmentioning

confidence: 99%

“…In a subsequent study using array comparative genomic hybridization Moinfar's group showed by that Ductal Intraepithelial Neoplasia low grade harbored changes common to lobular neoplasia, low nuclear grade ductal carcinoma in situ, and invasive carcinoma (loss of 16q, gain of 1q). 28 Simpson et al 24 found chromosomal alterations, as analyzed by comparative genomic hybridization, across the spectrum of columnar cell lesions (including some with architectural complexity that would alternatively be classified as atypical ductal hyperplasia by some experts). They noted a greater number of changes in lesions with cytologic atypia, hyperplasia, and/or architectural complexity.…”

Section: Pik3ca Mutations In Columnar Cell Lesionsmentioning

confidence: 99%

“…Recent loss of heterozygosity, comparative genomic hybridization, and immunohistochemical studies have suggested that columnar cell lesions, might represent the 'missing link' in low-grade breast cancer progression, as the earliest identifiable non-obligate precursor. 18,[22][23][24][25][26][27][28] In order to further address the pathogenetics of columnar cell lesions, we screened a cohort of columnar cell lesions, most with matched normal breast tissue and/or concurrent carcinoma, for a large panel of known activating point mutations, including PIK3CA and AKT1 mutations.…”

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Phosphatidylinositol-3-kinase pathway mutations are common in breast columnar cell lesions

et al. 2012

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The phosphatidylinositol-3-kinase pathway is one of the most commonly mutated pathways in invasive breast carcinoma, with PIK3CA mutations in B25% of invasive carcinomas, and AKT1 mutations in up to 5%. Ductal carcinoma in situ, and benign papillomas harbor similar mutations. However, activating point mutations in breast columnar cell lesions have been infrequently studied. Twenty-three breast resection specimens containing columnar cell lesions were identified; 14 with associated invasive carcinoma or carcinoma in situ. DNA extracts were prepared from formalin-fixed paraffin-embedded tissue and screened for a panel of point mutations (321 mutations in 30 genes) using a multiplex PCR panel with mass-spectroscopy readout. PIK3CA mutations were identified in 13/24 columnar cell lesions (54%) and 3/8 invasive carcinomas (37%). The mutation status of columnar cell lesions and associated carcinoma was frequently discordant. Of the 14 cases, only 5 demonstrated the same genotype in matched samples of columnar cell lesions and carcinoma (4 wild type, 1 PIK3CA H1047R). Interestingly, five patients had mutations in columnar cell lesions with wild-type carcinoma; two patients had different point mutations in columnar cell lesions and carcinoma. Only three cases had wildtype columnar cell lesion and mutated carcinoma. The 50% PIK3CA mutation prevalence in columnar cell lesions is greater than reported in most studies of invasive breast cancer. Further, columnar cell lesions and carcinoma were frequently discordant for PIK3CA/AKT1 mutation status. These findings raise interesting questions about the role of PIK3CA/AKT pathway in breast carcinogenesis, and the biologic/precursor potential of columnar cell lesions. The phosphatidylinositol-3-kinase pathway is activated in numerous cancer types and is one of the most commonly mutated pathways in invasive breast carcinoma. Activating mutations in the phosphatidylinositol-3-kinase catalytic subunit (PIK3CA) are present in B25% of invasive carcinomas, with mutations clustering in 'hotspots' in exon 9 (helical domain) and exon 20 (kinase domain). 1-10In addition, this pathway is activated by mutations in the plekstrin-homology domain of AKT1 in up to 5% of breast carcinomas, or by the loss of the phosphatase PTEN (phosphatase and tensin homolog) in nearly half of breast cancers.2,11 Several groups have demonstrated a similar frequency of mutations in breast carcinoma in situ, with paired invasive and in situ carcinoma from the same patient concordant for PIK3CA mutation status in 66-100% of tested cases.12-15 However, other breast proliferative or putative precursor lesions have been little studied. Li et al 13 found PIK3CA hotspot mutations in only 6% of 52 tested cases of Ductal Intraepithelial Neoplasia 1A-B lesions (DIN1A-B, atypical ductal hyperplasia and flat epithelial atypia, also known as columnar cell change with atypia). Our group previously identified PIK3CA/

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Section: Pik3ca Mutations In Columnar Cell Lesionsmentioning

confidence: 99%

Section: Pik3ca Mutations In Columnar Cell Lesionsmentioning

confidence: 99%

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Phosphatidylinositol-3-kinase pathway mutations are common in breast columnar cell lesions

et al. 2012

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“…Several authors have investigated aberrations on chromosome 16 in columnar cell lesions by loss of heterozygosity analysis, (array) comparative genomic hybridization or fluorescent in situ hybridization [5,6,[23][24][25][26]. The results of these studies vary strongly (see Table 1), most likely due to the small number of tested lesions, different types of columnar cell lesions studied and use of different DNA probes, varying definitions of columnar cell lesions and inter-observer variability in diagnosing columnar cell lesions [27,28].…”

Section: Introductionmentioning

confidence: 99%

Role of columnar cell lesions in breast carcinogenesis: analysis of chromosome 16 copy number changes by multiplex ligation-dependent probe amplification

et al. 2018

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Columnar cell lesions have been proposed as precursor lesions of low-grade breast cancer. The molecular characteristic of low-grade breast neoplasia is whole-arm loss of chromosome 16q. Copy number changes of 6 genes on 16p and 20 genes on 16q were analysed by multiplex ligation-dependent probe amplification in 165 lesions of 103 patients. Twenty-three columnar cell lesions and 19 atypical ducal hyperplasia lesions arising in columnar cell lesions were included, as well as cases of usual ductal hyperplasia, blunt duct adenosis, ductal carcinoma in situ, lobular neoplasia and invasive carcinoma. Usual ductal hyperplasia and blunt duct adenosis lacked whole-arm losses of 16q. In contrast, columnar cell lesions without atypia, columnar cell lesions with atypia, atypical ductal hyperplasia, low-grade ductal carcinoma in situ and low-grade invasive carcinomas increasingly harboured whole-arm losses of 16q (17%, 27%, 47% and 57%, respectively). However, no recurrent losses in specific genes could be identified. In several patients, columnar cell lesions and atypical ductal hyperplasia harboured similar losses as related ductal carcinoma in situ or invasive carcinomas within the same breast. There were indications for 16q breakpoints near the centromere. Whole-arm gains on 16p were relatively scarce and there was no relation between whole-arm gains of 16p and progression of lesions of the low-grade breast neoplasia family. In conclusion, columnar cell lesions (with and without atypia) often harbour whole-arm losses of 16q, which underlines their role as precursors in low-grade breast carcinogenesis, in contrast with usual ductal hyperplasia and blunt duct adenosis. However, no recurrent losses in specific genes could be identified, pointing to minor events in multiple tumour suppressor genes rather than major events in a single 16q gene contributing to low-grade breast carcinogenesis.

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“…Surgery is considered the standard treatment for PT (7). Invasive ductal carcinomas (IDC) of the breast accounts for 80% of all breast cancers, and these tumors demonstrate a worse survival rate than invasive lobular carcinoma (8), with overall 5-year survival rates of 84.1 and 85.6%, respectively (9). An IDC that is incidentally found within a borderline PT has been reported only once before in the literature (10).…”

Section: Introductionmentioning

confidence: 99%

Invasive ductal carcinoma within borderline phyllodes tumor with lymph node metastases: A case report and review of the literature

Zhang

Guo

et al. 2016

Oncology Letters

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Abstract. Phyllodes tumor (PT) is a rare type of biphasic fibroepithelial neoplasm that may coexist with a breast tumor in rare cases. In the current study, a 52-year-old female presented with a left breast lump. Mammography and sonographic examination results suggested a diagnosis of malignant tumor. Histological analysis revealed a borderline PT with invasive ductal carcinoma (IDC) within the tumor. Due to the presence of a single micrometastasis in three of the sentinel lymph nodes, the patient underwent modified radical mastectomy. The excised tumor contained triple negative breast cancer; therefore, postoperative treatment included six cycles of chemotherapy and 25 cycles of radiotherapy. The patient exhibited no recurrence and no metastatic disease at the 23-month follow-up examination. Thus, the present study discussed the case of a female patient that presented with IDC within borderline PT and reviewed the literature on this rare type of neoplasm. Various types of breast carcinoma have been identified to coexist with PT in different masses; however, no standard therapeutic regimen has been established for the coexistence of PT and breast cancer in the same mass. The present study indicates that determination of an appropriate treatment strategy predominantly depends on the characteristics of the individual breast tumor.

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Chromosomal aberrations as detected by array comparative genomic hybridization in early low-grade intraepithelial neoplasias of the breast

Cited by 12 publications

References 36 publications

Phosphatidylinositol-3-kinase pathway mutations are common in breast columnar cell lesions

Phosphatidylinositol-3-kinase pathway mutations are common in breast columnar cell lesions

Role of columnar cell lesions in breast carcinogenesis: analysis of chromosome 16 copy number changes by multiplex ligation-dependent probe amplification

Invasive ductal carcinoma within borderline phyllodes tumor with lymph node metastases: A case report and review of the literature

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