UMLS:C0007124 - FACTA Search

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Query: UMLS:C0007124 (ductal carcinoma in situ)
3,833 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Although mucinous carcinoma (MC) of the breast is considered to originate from ductal carcinoma, it is not known whether mucinous growth begins in the intraductal carcinoma or later in the invasive carcinoma. In this study, 33 MC (16 pure without any ductal components, 10 mixed Type I with an intraductal component, seven mixed Type II with a common invasive ductal carcinoma (IDC) component)) were examined to clarify the time when mucinous growth begins. Histochemical and immunohistochemical examinations of mucin revealed that mucinous growth can begin in the intraductal carcinoma and in the common IDC. Histological transition and clonality analysis using microsatellite markers supported that some MC originate from common IDC. The pure type of MC probably originates from the intraductal carcinoma, showing a micropapillary feature. Neuroendocrine differentiation, known to be associated with MC, seemed to create the main progress in the typical MC. Moreover, we analyzed the factors of a worse prognosis of mixed MC Type II, which was strongly suggested by the lymph node status. However, no explainable differences on the cell proliferating ability, or c-erbB-2 and p53 protein overexpression were found.
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PMID:Mucinous carcinoma of the breast: a multifaceted study with special reference to histogenesis and neuroendocrine differentiation. 1059 40

The p53 tumor suppressor gene is altered in approximately half of human cancers. Although p53 mutations are common in invasive breast carcinoma, few have been identified in breast carcinoma in situ (intraductal breast carcinomas). Most studies of p53 in breast carcinoma in situ are immunohistochemical studies of p53 staining in paraffin-embedded tissue sections. Few studies have isolated the tumor cells and subjected them to DNA sequence analysis. The current study was undertaken to characterize p53 in a cohort of breast carcinoma in situ cases, both with and without invasive disease. Fifty-eight frozen breast biopsy samples were used for these investigations. Twenty-seven cases had only ductal carcinoma in situ (CIS) and 31 cases had evidence of both invasive and in situ carcinoma. DNA sequence alterations in exons 2 through 11 of p53 were screened by the single-strand conformational polymorphism technique. Exons with altered mobility were sequenced. Among breast CIS cases without invasive disease, 22% had p53 mutations and 7% had DNA sequence alterations of unknown significance. Analysis of breast CIS with concurrent invasive disease demonstrated p53 mutations in 19% of cases and one (3%) DNA alteration of unknown significance. Each carcinoma having a p53 mutation in the breast CIS component had the identical mutation in the invasive component of the same tumor indicating a clonal relationship between the two tumor components. p53 protein overexpression was identified in 22% of pure intraductal breast carcinomas and in 35% of breast CIS with invasive disease. Comparison of immunostaining and DNA sequence alterations showed a significant association between overexpression and mutations (P = 0. 0037) in cases of CIS without invasion, and similarly between overexpression and mutations in cases of CIS with invasion (P = 0. 007). p53 mutations and p53 overexpression were relatively common in intraductal breast carcinomas but were not observed in adjacent normal breast lobules or ducts in 9 cases available for DNA analysis. The frequency of p53 alterations when comparing breast CIS with and without an invasive component indicated that p53 mutations usually occur before invasion during the progression of breast cancer, as is observed for a number of other adult solid tumors.
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PMID:p53 mutations and expression in breast carcinoma in situ. 1062 46

In this study, the expression of p53 (wild-type and mutated form) and bcl-2 in ductal carcinoma in situ (DCIS) and infiltrating ductal carcinoma (IDC) of the breast was evaluated by immunohistochemistry and PCR-SSCP and correlated with cellular kinetic parameters, i.e., mitotic index (MI) and apoptotic index (AI). The results showed a significant inverse correlation between p53 and bcl-2 expression in all cases of DCIS and IDC. In the DCIS group, two subgroups with different kinetic characteristics were identified. The first group was characterized by p53 positivity, bcl-2 negativity and high values of MI and AI; the other group was characterized by p53 negativity, bcl-2 positivity and low values of MI and AI. Conversely, in IDC some cases were p53 negative, bcl-2 positive and with high values of AI and MI, other cases were p53 positive, bcl-2 negative and with low AI and MI. Molecular biological analysis showed that p53 was wild-type in DCIS, while it was in the mutated form in IDC. These results suggest that in IDC mutated p53 contributes to a change in cellular kinetics and the selection of genetically aberrant cells, thereby favouring neoplastic progression. The coexistence of bcl-2 positivity and high AI could be explained by the presence of of apoptosis that work independently of bcl-2.
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PMID:Cellular kinetics and expression of bcl-2 and p53 in ductal carcinoma of the breast. 1076 54

17 beta-hydroxysteroid dehydrogenases (17 beta-HSDs) are involved in the interconversion of biologically active and inactive sex steroids and are considered to play important roles in the in situ metabolism of estrogen in various estrogen dependent tissues. 17 beta-HSD type 1 catalyzes primarily the reduction of estrone (E1) to estradiol (E2), whereas 17 beta-HSD type 2 catalyzes primarily the oxidation of E2 to E1. However, the possible biological roles of these estrogen metabolizing isozymes in human breast cancer, especially in carcinogenesis of the human breast, have not been examined in detail. Because of the potential roles of estrogens in the early stages of human breast carcinogenesis, we have examined the immunolocalization of 17 beta-HSD type 1 and type 2 isozymes and estrogen receptor alpha(ER alpha) in both normal human breast tissue and in breast cancers, including ductal carcinoma in situ (DCIS), proliferative disease without atypia (PDWA) or fibrocystic disease and atypical ductal hyperplasia (ADH). We also correlated these findings with clinicopathological findings, Ki67 antigen, progesterone receptor (PR), c-erbB-2, and p53. 17 beta-HSD type 2 immunoreactivity was sporadically detected in non-proliferative or Ki67 negative ductal epithelia of normal breast, but rarely in breast carcinoma cells. 17 beta-HSD type 1 immunoreactivity was detected in 12/22 (54.5%) PDWA cases, 8/26 (30.8%) ADH cases, and 25/40 (62.5%) DCIS cases, respectively. 17 beta-HSD type 1 immunoreactivity was not statistically correlated with the age of the patients, Ki67 labeling index (LI), and PR LI, p-53 and c-erbB-2 immunoreactivity. There was no significant correlation between ER alpha LI and 17 beta-HSD type 1 immunoreactivity. There was a positive correlation between ER alpha and Ki67 LI in PDWA, whereas a negative correlation was detected between ER alpha and Ki67 LI in DCIS. There was no correlation between ER alpha and Ki67 LI in ADH. These results suggest that in human breast epithelial cells, development of ADH and DCIS may be associated with the loss and/or deviation of oestrogen dependent regulation of cell proliferation.
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PMID:17 beta-Hydroxysteroid dehydrogenase type 1 and type 2 in ductal carcinoma in situ and intraductal proliferative lesions of the human breast. 1081 Apr 3

We present ten cases of mammographically detected lobular carcinoma in situ (LCIS), involving a single area of variable size (up to a quadrant) in seven cases and the entire gland in three cases. Histologically, calcifications were associated with necrotic central areas within the in situ carcinomatous foci. Multiple foci of LCIS were observed in all five cases in which mastectomy had been performed. Cytologically, the lesions were characterized by a solid proliferation of round noncohesive cells with nuclei of intermediate size. Immunocytochemically, all cases were E-cadherin and p53 negative, and c-ErbB-2, GCDFP-15 and estrogen receptor positive. The proliferation index, evaluated with Ki67, was in the low range. Four cases were associated with foci of infiltrating lobular carcinoma (ILC). These findings contradict the commonly held opinion that LCIS is not mammographically detectable because of its lack of necrosis and calcification. This study documents the existence of a variant of LCIS exhibiting the mammographic features and central necrosis classically associated with ductal carcinoma in situ (DCIS), while retaining the spatial distribution, cytological composition and immunocytochemical features of lobular carcinoma.
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PMID:Mammographically detected in situ lobular carcinomas of the breast. 1088 35

Pancreatic cancer belongs to the neoplasms which are characterised by increasing morbidity and mortality. Five-year survival rates of about 0.4% are the norm, and little has changed in the last 70 years. Important etiological factors are age, sex, diet, tobacco smoking, alcohol abuse, occupation and chemical exposure, hereditary chronic pancreatitis, and previous surgery (cholecystectomy and gastrectomy). The majority of exocrine tumours of the pancreas are malignant and 80-90% of them comprise ductal adenocarcinomas. The development and growth of pancreatic carcinoma appears to be caused by a progressive accumulation of multiple genetic abnormalities. This includes oncogene (K-ras) activation, loss of tumour-suppressor p53 gene function and overexpression of growth factors and their ligands. The morphological background for the development of pancreatic carcinoma is ductal epithelial hyperplasia. Current molecular studies have resulted in the identification of cell clones exhibiting the same genetic alterations (K-ras and p53 mutations) as in infiltrating pancreatic carcinoma. Pancreatic intraepithelial neoplasia is only partially defined. The purpose of our study was to evaluate Ki-67 proliferative index and HER-2/neu gene expression in pancreatic intraepithelial proliferative lesions as a sign of increasing epithelial proliferation and dysplasia. Additionally we made an attempt to apply morphometry in demarcating between intraepithelial proliferations of "reactive" type and proliferations with tendency towards progression to cancer. Another aim of the study was to evaluate the expression of bcl-2 and p53 genes in various types of pancreatic intraepithelial proliferations and in pancreatic cancer and to answer the question whether they interact in the process of pancreatic intraepithelial neoplasia. We have also undertaken investigations aiming at determination of the CD44s gene and its v6 isoform expression in intraductal and invasive pancreatic carcinoma, attempting to correlate this expression with the p53 gene mutations. The results of our study indicate that intraductal pancreatic proliferations form a group of heterogeneous lesions possessing different proliferative activity of cells, karyometric features and HER-2/neu, bcl-2 and p53 genes expression. The precancerous lesion in the pancreas may be atypical papillary hyperplasia, which is similar to intraductal carcinoma with respect to the proliferative activity of cells and HER-2/neu, bcl-2 and p53 expression. Pancreatic carcinoma is characterised by high p53, CD44s and CD44v6 expression and low bcl-2 expression. CD44 and p53 genes expression is independent and between bcl-2 and p53 expression there is an inverse correlation. The p53 and CD44v6 expression is the higher the lower is the histological grade of the pancreatic carcinoma.
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PMID:[Morphologic, morphometric and immunohistochemical studies on pancreatic intraductal hyperplasia and infiltrating carcinoma]. 1090 69

Breast cancer is considered to display a high degree of intratumor heterogeneity, without any obvious morphological and pathological steps to define sequential evolution, and its progression may vary among individual tumors. In an attempt to elucidate these etiological and phenotypic complexities, the present study, based on the fundamental concept that genomic instability is the engine of both tumor progression and tumor heterogeneity, was conducted to test the hypothesis that breast cancer pathogenesis is driven by double-strand break (DSB)-initiated chromosome instability (CIN). The rationale underlying this hypothesis is derived from the clues provided by family breast cancer syndromes, in which susceptibility genes, including p53, ATM, BRCA1 and BRCA2, are involved within the common functional pathway of DSB-related checkpoint/ repair. Because genomic deletion caused by DSB is reflected in the genetic mechanism of loss of heterozygosity (LOH), this genome-wide LOH study was conducted, using 100 tumors and 400 microsatellite markers. To minimize the effect of heterogeneity within tumors, the experimental technique of laser capture microdissection was used to ensure that genetic and phenotypic examinations were based on the same tumor cells. Support for our hypothesis comes from the observations that: (a) the extent of DSB-initiated CIN in tumors significantly increased as tumors progressed to poorer grades or later stages; (b) in the sequential steps toward CIN, the loci of p53 and ATM, the key checkpoint genes against DSB, were lost at the earliest stage; and (c) many loci identified to be important in breast tumorigenesis were the genomic sites possibly harboring the genes involved in DSB-related checkpoint/repair (including RAD51, RAD52, and BRCA1) or CIN (including FA-A, FA-D, and WRN), and a higher number of these loci showing LOH was significantly associated with increased level of DSB-initiated CIN (P < 0.0001). Breast cancers are thus considered to be sequentially progressive with CIN. However, CIN might also cause genetic heterogeneity, which was revealed by the findings that LOH at some markers was observed only in the component of ductal carcinoma in situ but not in the invasive component of the same tumors. In addition, some markers were found to preferentially lose at specific tumor grades, implying their contribution to genetic heterogeneity during tumor development. Therefore, this study suggests that breast cancer progression is clonal with regard to CIN, but different breast cancers would present distinct molecular profiles resulting from genetic heterogeneity caused by CIN.
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PMID:Genome-wide search for loss of heterozygosity using laser capture microdissected tissue of breast carcinoma: an implication for mutator phenotype and breast cancer pathogenesis. 1091 64

In a consecutive and unselected series of 178 cases of carcinoma in situ of the breast (CIS), comprising both ductal (DCIS) and lobular type (LCIS), and a series of 48 cases of invasive carcinoma (IC) with predominance of DCIS, the association between histopathology, immunohistochemical markers (ER, PgR, MIB-1, c-erbB-2, and p53), and DNA ploidy was investigated, in order to discriminate biologically different groups. In DCIS, significant correlation was shown between large nuclear size and comedonecrosis, both of which showed also strong association to DNA aneuploidy, high proliferation activity, low steroid receptor content, and overexpression of c-erbB-2 and p53 factors that may indicate an aggressive behavior. Small nuclear CIS, whether LCIS or DCIS, on the contrary, were DNA diploid with low proliferation, and no cases showed overexpression of c-erbB-2 and p53. Heterogeneity with respect to the investigated parameters was also a frequent finding that may reflect a development complexity. In IC, comparison of the DCIS and the invasive component showed similar patterns. No significant differences were shown between DCIS without and with invasion. This may indicate that none of the investigated parameters on its own are essential for the event of invasion.
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PMID:Carcinoma in situ of the breast: correlation of histopathology to immunohistochemical markers and DNA ploidy. 1093 Jan 9

Germline mutations in the breast cancer-associated genes BRCA1 and BRCA2 confer a lifetime risk of malignancy. Distinctive morphological features have been attributed to these familial tumours; however, in sporadic breast cancer, the inter-relationship between loss of heterozygosity (LOH) of these loci and tumour morphology remains to be fully elucidated. We studied a series of 120 sporadic breast carcinomas using microsatellite markers to identify LOH of BRCA1, BRCA2, p53 and PTEN. The associations between loss at each of the loci were examined and related to tumour morphology. LOH of the 4 loci did not occur independently; there were highly significant associations between LOH of BRCA1 and both BRCA2 (p < 0.001) and p53 (p < 0.001). LOH at all 4 loci was significantly associated with a high degree of nuclear pleomorphism. Tumours with LOH of BRCA1 also had high mitotic indices, few tubules and a paucity of DCIS, all of which are morphological features similar to those described for familial cases. Following Bonferroni's correction for multiple tests, we found that the tumours with LOH of BRCA1 were still significantly associated with a high mitotic index (p = 0.0006) and a high degree of nuclear pleomorphism (p = 0.001).
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PMID:Association between loss of heterozygosity of BRCA1 and BRCA2 and morphological attributes of sporadic breast cancer. 1100 69

To clarify the clinicopathological features of an atypical cystic duct (ACD) as defined by Tsuchiya's criteria as a precancerous lesion of the breast, we used 200 whole mammary gland serial sections of breast cancer. Forty-four (22%) of the 200 breast cancer patients had ACD breast lesions. The frequency of patients with ACD increased in premenopausal women (P = 0.001). There was no correlation between the ACD-present group and the ACD-absent group for immunohistochemical status of the estrogen receptor (ER), progesterone receptor (PgR), p53, or c-erbB2; Ki-67 labeling index of cancer tissues; size of tumor, or lymph node metastases. A number of ACD lesions displayed continuity to cancer lesions. In 500 serial sections of a paraffin-embedded tissue of a ACD case at 3 microm intervals, an apparent transition from ACD into ductal carcinoma in situ was observed. Immunohistochemical analysis using alpha-smooth muscle actin showed that myoepithelial cells of ACD stained strongly, and their nuclei and cytoplasm were thinning. In 16 of the 44 (36%) ACD-present patients, carcinoma cells stained positive for p53. Within those 16 cases, 12 cases (75%) were positive for p53 in ACD lesions. There was a significant correlation between the expression of p53 protein in malignant cells and ACD (P = 0.001). All 44 ACD lesions had no staining of c-erbB2, regardless of staining in malignant lesions. The mean Ki-67 labeling index of ACD lesions was low (0.3%), suggesting that ACD had a low proliferative rate. We suggest that ACD is the precancerous breast lesion because of a histologic continuum between ACD and malignancy, and because of p53 protein expression in ACD.
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PMID:Clinicopathological characteristics of atypical cystic duct (ACD) of the breast: assessment of ACD as a precancerous lesion. 1110 51

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