Papillary lesions of the breast: a molecular progression?

Cristofano, Claudio Di; Mrad, Karima; Zavaglia, Katia; Bertacca, Gloria; Aretini, Paolo; Cipollini, Giovanna; Bevilacqua, Generoso; Romdhane, K. Ben; Cavazzana, Andrea

doi:10.1007/s10549-004-3003-3

Cited by 45 publications

(34 citation statements)

References 18 publications

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“…Although intra-tumoral heterogeneity may result in discordant cytogenetic profiles, this minor effect may be considered negligible when distinguishing malignant from benign samples by our 14 method. Moreover, cytogenetic profiles of five cancer cases showed 16q loss and 1q gain as the most frequently altered region, which is a typical cytogenetic profile of papillary breast carcinomas, as reported previously [16][17][18][19][20].…”

Section: Discussionsupporting

confidence: 80%

“…There are many reports indicating the presence of genomic alterations in intracystic papillary carcinoma of the breast [16][17][18][19][20]. We recently reported that genome-wide copy number aberrations could easily be detected by array comparative genomic hybridization (aCGH), which could then be used to quantify GIN, and that intracystic papillary carcinoma harbors significant GIN compared with intracystic papilloma [21].…”

Section: Introductionmentioning

confidence: 99%

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A novel diagnostic method targeting genomic instability in intracystic tumors of the breast

et al. 2014

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Section: Discussionsupporting

confidence: 80%

Section: Introductionmentioning

confidence: 99%

A novel diagnostic method targeting genomic instability in intracystic tumors of the breast

et al. 2014

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“…Of the 104 cases, 30 were mammotome core needle biopsies, all done for calcifications (14-gauge) and 74 were ultrasound-guided (16-, 18-, or 20-gauge). The average number of ultrasound-guided core cylinders obtained per patient was 5 (range, [3][4][5][6][7][8][9][10][11][12]; for mammotome core needle biopsy it was 15 (range, [10][11][12][13][14][15][16][17][18][19][20]. The diagnoses on the excision specimens were as follows: no residual intraductal papillomas, 16 (15.3%); residual intraductal papillomas, 71 (68.3%); atypical duct hyperplasia, 8 (7.7%); ductal carcinoma in situ, 6 (5.8%); and invasive carcinoma, 3 (2.9%).…”

Section: Resultsmentioning

confidence: 99%

Excision is indicated for intraductal papilloma of the breast diagnosed on core needle biopsy

Jaffer

Nagi

Bleiweiss

2009

Cancer

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BACKGROUND: Although it has been accepted that intraductal papillomas with atypia or malignancy diagnosed on core needle biopsy require surgical excision, the management of pure intraductal papillomas has been controversial. Because some series reported a small but definite incidence of atypia or malignancy, whereas others claimed that radiologic follow‐up was adequate, this study evaluated results of excision of all pure intraductal papillomas diagnosed on core needle biopsy at this institution. METHODS: By using computerized pathology files from January of 2000 to December of 2004, 200 cases of intraductal papillomas on core needle biopsy were identified. Information regarding excision was available in 104 cases. All specimens were reviewed to confirm both the diagnoses as well as the presence of biopsy site changes in excision specimens, and the findings were correlated with radiologic data. RESULTS: The age of the patients ranged from 25 to 82 years (mean, 55.5). The diagnoses on excision were as follows: intraductal papillomas = 71 cases (68.3%), no residual intraductal papillomas = 16 (15.3%), atypical duct hyperplasia = 8 (7.7%), ductal carcinoma in situ = 6 (5.8%), and invasive carcinoma = 3 (2.9%). In cases with atypia or malignancy, these findings were adjacent to but not in the biopsy site. In cases with atypical duct hyperplasia or ductal carcinoma in situ, a spectrum of histologic changes ranging from florid to atypical duct hyperplasia (14 cases), to ductal carcinoma in situ (6 cases) were present, all involving intraductal papillomas. CONCLUSIONS: The upstage rate of pure intraductal papillomas on core needle biopsy to atypia or malignancy on excision was 16.4%. Because of sampling error and the close proximity of atypia or malignancy to the intraductal papillomas (suggesting precancerous potential), excision was recommended of these lesions diagnosed on core needle biopsy. Close radiologic‐pathologic correlation was important in the evaluation of these lesions. Cancer 2009. © 2009 American Cancer Society.

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“…Several subsequent studies looking at large-scale chromosomal alterations (using methods of fluorescence in situ hybridization, loss of heterozygosity, and comparative genomic hybridization) have generated conflicting data regarding the presence or frequency of alterations in benign papillary lesions. [4][5][6][7][8][9] Thus, it is unclear whether papillary neoplasms harbor genetic changes common to the pathways of breast cancer progression, and it remains undetermined whether papillary lesions represent precursors of breast carcinoma.…”

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confidence: 99%

High prevalence of PIK3CA/AKT pathway mutations in papillary neoplasms of the breast

et al. 2010

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Papillary lesions of the breast have an uncertain relationship to the histogenesis of breast carcinoma, and are thus diagnostically and managerially challenging. Molecular genetic studies have provided evidence that ductal carcinoma in situ and even atypical ductal hyperplasia are precursors of invasive carcinoma. However, papillary lesions have been seldom studied. We screened papillary breast neoplasms for activating point mutations in PIK3CA, AKT1, and RAS protein-family members, which are common in invasive ductal carcinomas. DNA extracts were prepared from sections of 89 papillary lesions, including 61 benign papillomas (28 without significant hyperplasia; 33 with moderate to florid hyperplasia), 11 papillomas with atypical ductal hyperplasia, 7 papillomas with carcinoma in situ, and 10 papillary carcinomas. Extracts were screened for PIK3CA and AKT1 mutations using mass spectrometry; cases that were negative were further screened for mutations in AKT2, BRAF, CDK, EGFR, ERBB2, KRAS, NRAS, and HRAS. Mutations were confirmed by sequencing or HPLC assay. A total of 55 of 89 papillary neoplasms harbored mutations (62%), predominantly in AKT1 (E17K, 27 cases) and PIK3CA (exon 20 4exon 9, 27 cases). Papillomas had more mutations in AKT1 (54%) than in PIK3CA (21%), whereas papillomas with hyperplasia had more PIK3CA (42%) than AKT1 (15%) mutations, as did papillomas with atypical ductal hyperplasia (PIK3CA 45%, AKT1 27%, and NRAS 9%). Among seven papillomas with carcinoma in situ, three had AKT1 mutations. The 10 papillary carcinomas showed an overall lower frequency of mutations, including 1 with an AKT1 mutation (in a tumor arising from a papilloma), 1 with an NRAS gene mutation (Q61H), and 2 with PIK3CA mutations (1 overlapping with the NRAS Q61H). These findings indicate that approximately two-thirds of papillomas are driven by mutations in the PI3CA/AKT pathway. Some papillary carcinomas may arise from these lesions, but others may have different molecular origins.

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Papillary lesions of the breast: a molecular progression?

Abstract: Our data suggest an involvement of chromosome 16 mutations in the early steps of breast papillary tumorigenesis. TP53 deletion and possibly LOH at 16q23 appear to play a role as progression factors, being they significantly associated with malignant transformation of breast papilloma.

Cited by 45 publications

References 18 publications

A novel diagnostic method targeting genomic instability in intracystic tumors of the breast

A novel diagnostic method targeting genomic instability in intracystic tumors of the breast

Excision is indicated for intraductal papilloma of the breast diagnosed on core needle biopsy

High prevalence of PIK3CA/AKT pathway mutations in papillary neoplasms of the breast

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