Disease relevance of Carcinoma, Intraductal, Noninfiltrating

• We previously showed that a p53 mutation present in invasive breast cancer was found in all surrounding areas of ductal carcinoma in situ (DCIS) but not in areas of hyperplasia or normal breast epithelium [1].
• Our finding that p53 mutations can occur before the development of invasive breast cancer, particularly in DCIS of high histologic grade, has potentially important implications for prevention and treatment [1].
• These results demonstrate for the first time that specific TN isoforms are expressed in invasive breast carcinomas and that these isoforms are identified in a subset of DCIS and suggest that detection of TN16 and/or TN14/16 may be used as a predictor for invasion [2].
• We determined, by serial analysis of gene expression (SAGE) analysis of normal and DCIS (ductal carcinoma in situ) mammary epithelial cells, that psoriasin and several other genes implicated in psoriasis are aberrantly expressed in high-grade, comedo DCIS [3].
• Furthermore, maspin was expressed in 23 of 24 tumor specimens obtained from pancreatic cancer patients as well as all high-grade precancerous lesions (PanIN3 and intraductal carcinoma extension) [4].

Psychiatry related information on Carcinoma, Intraductal, Noninfiltrating

• The role of tamoxifen is currently under study, and although approved by the FDA for "risk reduction," its use in patients with DCIS is uncertain [5].

High impact information on Carcinoma, Intraductal, Noninfiltrating

• In DCIS lesions, increased levels of HIF-1 alpha were statistically significantly associated with increased microvessel density [6].
• In the present investigation, we studied patients with DCIS, but without invasive breast cancer, to determine the spectrum of DCIS types that can harbor a p53 mutation [1].
• METHODS: Formalin-fixed, paraffin-embedded tissues from 94 patients with DCIS were evaluated histologically for the predominant cellular architectural pattern, degree of necrosis, and nuclear grade [1].
• The frequency of p53 missense mutations was statistically significantly different among the three overall histologic grade categories (zero [0%] of 49 with low-grade DCIS, one [4.35%] of 23 with intermediate-grade DCIS, and nine [40.9%] of 22 with high-grade DCIS; df = 2 and P<.0001) [1].
• Estrogen treatment of the xenograft-bearing mice had no effect on the high level of cell proliferation observed in estrogen receptor-negative, comedo DCIS specimens (two-sided P = .89) [7].

Chemical compound and disease context of Carcinoma, Intraductal, Noninfiltrating

• CONCLUSION AND IMPLICATION: Estrogen receptor-negative, comedo DCIS lesions appear to be estrogen independent; therefore, antiestrogen (e.g., tamoxifen) therapy may not benefit patients with comedo DCIS [7].
• Overall, a 56% reduction in epithelial proliferation was seen with Iressa in EGFR-positive DCIS [8].
• Epidermal growth factor receptor (EGFR) is a receptor tyrosine kinase that is involved with mitogenesis and is expressed in ER-negative DCIS [8].
• A conditional tetracycline-responsive transgenic mouse model with deregulated estrogen receptor alpha expression in mammary epithelial cells developed ductal hyperplasia (DH), lobular hyperplasia, and ductal carcinoma in situ (DCIS) by 4 months of age [9].
• Of the 40 monkeys administered anagestone acetate and mestranol, 20 (50%) developed proliferative atypias; the atypias ranged from mild to severe and included five resembling intraductal carcinoma in human breast [10].
• Results of our study suggest that intratumoral concentrations of estradiol and DHT are increased in DCIS, which is possibly due to intratumoral production of these steroids [11].
• Thirty-two DCIS exhibited a luminal phenotype; 21 were ERBB2 positive, and 4 were ERBB2/estrogen receptor (ER) negative with 1 harboring a bona fide basal-like phenotype [12].
• Exemestane reduces proliferation in ER-positive DCIS [13].

Biological context of Carcinoma, Intraductal, Noninfiltrating

• RESULTS: DCIS from 10 of 94 patients were found to contain p53 missense mutations [1].
• We reported earlier that 100% of female ACI (August/Copenhagen/Irish) rats treated with essentially physiological serum levels of 17beta-estradiol lead to mammary gland tumors with histopathologic, cellular, molecular, and ploidy changes remarkably similar to those seen in human DCIS and invasive sporadic ductal BC [14].
• Mechanisms other than gene amplification may be responsible for increased cyclin D1 protein in DCIS, especially in low grade DCIS [15].
• A significant fraction of untreated DCIS will evolve into invasive cancer. ras homologue I (ARHI) is an imprinted tumor suppressor gene that is expressed in normal breast epithelial cells but absent or down-regulated in breast cancer cells [16].
• Increased expression of IAP, (leading to reduced apoptosis) may explain the effect of COX-2 in increasing recurrence of DCIS after surgical treatment [17].

Anatomical context of Carcinoma, Intraductal, Noninfiltrating

• Epithelial cells from morphologically clear-cut normal ducts and lobules, DCIS, and IDC were also microdissected [18].
• In 51 cases, uPAR immunoreactivity was observed, and in 49 of these specimens, a population of periductal tissue macrophages showed pronounced uPAR immunoreactivity in areas with infiltrating and intraductal carcinoma [19].
• BACKGROUND: We determined the presence or absence of and clinical significance of cytokeratin-positive cells in the lymph nodes of patients who had had mastectomies for ductal carcinoma-in-situ [20].
• We evaluated 25 intraductal papillomas and 18 papillary carcinomas (invasive, 4; micropapillary ductal carcinoma in situ [DCIS], 5; cases originally classified as intracystic/intraductal papillary carcinoma, 9) by calponin, smooth muscle myosin heavy chain (SMM-HC), and p63 immunostains [21].
• Variant of intraductal carcinoma (with scant mucin production) is of main pancreatic duct origin: a clinicopathological study of four patients [22].

Gene context of Carcinoma, Intraductal, Noninfiltrating

• Higher levels of MMP-26 mRNA were also detected in DCIS cells by in situ hybridization [23].
• Double immunofluorescence labeling and confocal laser scanning microscopy revealed that MMP-26 was colocalized with MMP-9, TIMP-2, and TIMP-4 in DCIS cells [23].
• Our results demonstrate that induction of CA IX and CA XII occurs in regions adjacent to necrosis in DCIS [24].
• In addition, the expression levels of ER-alpha and N-CoR were significantly higher in the intraductal carcinomas than those in the invasive ductal carcinomas [25].
• Immunohistochemistry revealed that there was no loss of reactivity for the mismatch repair proteins, MLH1, MSH2, and PMS2, in the DCIS cases [26].
• BRCA mutations were less frequent in women with DCIS not selected for family history or age at diagnosis than in women with IBC [27].

Analytical, diagnostic and therapeutic context of Carcinoma, Intraductal, Noninfiltrating

• We did a double-blind randomised controlled trial to find out whether lumpectomy, radiation therapy, and tamoxifen was of more benefit than lumpectomy and radiation therapy alone for DCIS [28].
• Archival primary breast carcinomas (n = 57), adjacent DCIS (n = 14) and DCIS alone (n = 2) were analyzed for COX-2 and HER2 expression by immunohistochemistry using specific monoclonal antibodies [29].
• Using the PCR, we examined DNA extracts from microdissected stromal and epithelial tissues of 11 breast samples containing DCIS, including five cases associated with IDC [18].
• In contrast, treatment of mice bearing ER+ DCIS xenografts with 17beta-estradiol raised both the AI (1.03% versus 0.40%, P = 0.03) and LI (11.0% versus 5.1%, P = 0.007) compared with controls [30].
• By Southern blot analysis, cyclin D1 gene amplification was detected in 10 per cent (3/32) of DCIS cases [31].

References