Gene/Protein Disease Symptom Drug Enzyme Compound
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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)

Identification of myoepithelial cells using antibodies to cytoskeletal proteins, such as smooth muscle myosin heavy chain (SMM-HC) and calponin, can play an important role in distinguishing invasive carcinoma from its histologic mimics. However, antibodies to these proteins may also cross-react with stromal myofibroblasts and vascular smooth muscle cells. It has recently been demonstrated that myoepithelial cells express the nuclear protein, p63, a member of the p53 gene family. We compared the patterns of reactivity of antibodies with p63, calponin, and SMM-HC on 85 breast lesions, including 11 cases of sclerosing adenosis, 33 cases of ductal carcinoma in situ, including 10 that showed microinvasion, 6 cases of lobular carcinoma in situ, and 35 cases of infiltrating ductal carcinoma. All three antibodies were positive on the vast majority of myoepithelial cells in all cases. A small minority of cases showed focal gaps in the revealed myoepithelial cell layer, reflected in discontinuous positive immunostaining around noninvasive epithelial nests (including ductal carcinoma in situ). No case showed p63 expression by myofibroblasts or vascular smooth muscle cells, whereas myofibroblasts expressed, in 8% and 76% of cases, SMM-HC and calponin, respectively. Although no tumor cell reactivity was noted with antibodies to calponin or SMM-HC, tumor cells in 11% of cases showed at least focal p63 expression. And although antibodies to p63 offer excellent sensitivity and increased specificity for myoepithelial detection relative to antibodies to calponin and SMM-HC, they have the following diagnostic limitations: 1) they occasionally demonstrate an apparently discontinuous myoepithelial layer, particularly around ductal carcinoma in situ, and 2) they react with a small but significant subset of breast carcinoma tumor cells. p63 may represent a myoepithelial marker that can complement or replace SMM-HC and/or calponin in the analysis of difficult breast lesions.
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PMID:Immunohistochemical distinction of invasive from noninvasive breast lesions: a comparative study of p63 versus calponin and smooth muscle myosin heavy chain. 1250 30

P63, a p53 homologue, is considered to be a marker of myoepithelial cells in breast tissue. This study was carried out to determine the sensitivity of p63 in detecting myoepithelial cells in DCIS and to compare the results obtained with smooth-muscle actin (1A4) in an attempt to verify the reliability of p63 as a possible marker of microinvasion in breast carcinoma. Fifteen DCIS of the breast were submitted to immunohistochemical analysis with anti-p63 and 1A4 antibodies and to a double immunolabeling study using p63 with 1A4. The double immunolabeling study showed that the same cells positive for p63 were also positive for 1A4. The three cases of DCIS with micro-invasion were negative for p63 and 1A4 in the foci of invasiveness. P63 staining was continuous in five of twelve cases of DCIS without microinvasion, being focal and discontinuous in 6 cases and completely negative in one case. Smooth-muscle actin staining was continuous in nine of twelve cases, including the five cases positive for p63. Smooth-muscle actin was focal and discontinuous in only two cases, which were also discontinuous for p63. The DCIS negative for p63 was also negative for 1A4. In conclusion, our results confirm the data of literature that p63 is a specific marker of myoepithelial cells in breast tissue. However, p63 is not as sensitive as 1A4 in staining myoepithelial cells and lack of p63 expression cannot be used as a reliable marker of invasiveness in ductal carcinoma in situ of the breast.
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PMID:Is p63 reliable in detecting microinvasion in ductal carcinoma in situ of the breast? 1270 42

Abnormalities in G1/S transition in cell cultures have been attributed to alterations in ErbB (erythroblastic leukaemia viral [v-erb-b] oncogene homologue, avian) signalling, cyclin D1 overexpression or disturbance of the p21(WAF1) (p21)-mediated cell cycle arrest induced by p53. To investigate the significance of these mechanisms on an early stage of human breast tumour growth, we studied the expression of EGFR (ErbB1), HER-2/neu (ErbB2), cyclin D1, p21 and p53 as well as oestrogen (ER) and progesterone receptor (PgR) in paraffin sections of 45 ductal carcinoma in situ (DCIS) by immunohistochemistry. Cell proliferation was assessed by immunohistochemical quantification of Ki-67. Five cases with cyclin D1 overexpression were analysed by FISH for CCND1 amplification. Increased proliferative activity was observed in 46% of DCIS. It was correlated with the expression of EGFR and HER-2/neu (p < 0.05), but neither with cyclin D1 and p21 overexpression nor with p53 accumulation. ErbB positive status was associated with p21 overexpression (p < 0.05). In addition we found a correlation between the overexpression of p21 and cyclin D1 restricted to ErbB-positive cases (p = 0.013). ErbB-negative tumours with increased proliferative activity were ER and cyclin D1 positive. No CCND1 amplification was detected in the analysed cases. In conclusion, our data support that EGFR and HER-2/neu play an important role in cell cycle control in DCIS. p21 appears to be a potential mediator of ErbB signalling. We propose that cyclin D1 could be indirectly induced by ErbB signalling through p21. Besides, ER-mediated upregulation of cyclin D1 seems to be a possible mechanism of maintaining cell proliferation in DCIS in case of EGFR- and HER-2/neu-negativity.
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PMID:EGFR, HER-2/neu, cyclin D1, p21 and p53 in correlation to cell proliferation and steroid hormone receptor status in ductal carcinoma in situ of the breast. 1282 53

The aim of this study was to assess the levels of cell cycle regulatory proteins p21waf1 (p21), p53, Cyclin A, Cyclin D1 and Ki-67 to see whether they correlated with recurrence-free survival (RFS). From 1982 to 1996, 50 patients aged less than 51 years underwent lumpectomy followed by radiotherapy for a pure ductal carcinoma in situ (DCIS). For each case, the following immunohistochemical stains were carried out: Ki-67, Cyclin A, Cyclin D1, p53 and p21waf1 (p21). The percentage of positive nuclei was assessed. Multiple combinations of these factors were performed; in particular, we called the sum of Ki-67 and Cyclin A a global proliferation factor (GPF). Correlations with classical clinicopathological data were assessed. After a multivariate analysis, only GPF, Van Nuys Prognostic Index (VNPI) grade and mitotic index were independent predictive factors of recurrence in the whole population. In the population with close surgical margins, when the GPF level was less than the 25th percentile or more than the 75th percentile recurrence was low. In this preliminary study, GPF seems to be of interest to help in the decision process in the post-surgical management of the patient.
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PMID:Immunohistochemical study of cell cycle regulatory proteins in intraductal breast carcinomas--a preliminary study. 1282 38

Microinvasive ductal carcinoma of the breast, namely ductal carcinoma in situ with microinvasion (T1mic) as defined by the American Joint Committee on Cancer (AJCC) Staging Manual, is a rare disease, although it is increasing because of widespread use of mammography. The aim of the present study was to describe the clinicopathological and immunohistochemical features of this entity. Twenty-eight patients who were diagnosed as T1mic from January 1997 to August 2002 were studied by using 3-5 mm-thick serial sections with hematoxylin-eosin staining. Immunohistochemical staining for the estrogen receptor (ER), progesterone receptor (PR), p53, Ki-67, and HER-2 were performed. All 28 patients were female, with a mean age of 48.8 years. Twenty-six patients (93%) revealed mammographic abnormalities on routine examination. All foci of the invasions were measured using an ocular micrometer. Invasive foci consisted of isolated cells or cell clusters, or appeared as a tongue-like projection of tumor through the basement membrane of the duct of ductal carcinoma in situ (DCIS). The mean number of invasive foci was 3, and the mean size was 0.6 mm. We found that high nuclear grade and predominant comedo subtype of DCIS components were 57.1% and 46.4%, respectively. Twenty-four cases (86%) demonstrated necrosis of DCIS components. Microinvasion was often associated with periductal stromal reaction (71.5%) and/or a lymphocytic infiltration (78.6%). All patients, excluding two, received axillary resection (the mean number of lymph nodes examined per case was 12), and none had lymph node metastasis. The positive expression of ER and PR strongly related to low grade nuclei and non-comedo subtype; however, the positive expression of HER-2 and P53 related to high grade nuclei and comedo subtype (P<0.01). Ki-67 expression was significantly higher in the high grade nuclei group than in the low grade group (P<0.01). Our study suggested that high nuclear grade and comedo DCIS were more aggressive and more common with microinvasion, and that microinvasion is more likely to be multifocal.
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PMID:Microinvasive ductal carcinoma (T1mic) of the breast. The clinicopathological profile and immunohistochemical features of 28 cases. 1282 6

Carcinoma in situ of the breast (CIS) comprise a heterogenous group of lesions, covering a wide spectrum of clinical conditions and histopathological changes. With respect to biological behavior, CIS range from biologically aggressive lesions with a substantial risk of progression into invasive carcinoma (IC), to lesions with a very low malignant potential. Two main types of CIS are described--ductal carcinoma in situ (DCIS) and lobular carcinoma in situ (LCIS). Previous studies of CIS indicate that approximately a third will subsequently develop IC. Autopsy studies indicate that CIS is frequently occurring and it was estimated that about 20% of all women will develop CIS during lifetime. Only a minor fraction is ever diagnosed, although the incidence of DCIS is increasing, especially related to mammography screening. The lack of knowledge about the biological significance of the histopathological subtypes was the background of the present study. In 1982, a nationwide, prospective study of CIS (protocol DBCG 82-IS) was initiated by the Danish Breast Cancer Cooperative Group (DBCG). From this protocol, the group of patients treated with breast conservation surgery (BCS) constituted the material for clinico-histological investigation. A total of 275 women were included in the period 1982-89. Follow-up studies showed that recurrence rate was significantly related to nuclear size of the primary lesion. Since nuclear changes might be related to DNA content and, furthermore, many invasive breast carcinomas were shown to be DNA aneuploid, flow cytometric (FCM) DNA ploidy analysis was performed in a series of DCIS lesions. More than 80% of these lesions were DNA aneuploid, with a distribution similar to that found in invasive carcinomas. This finding raised the hypothesis that the DNA pattern of an invasive carcinoma was already established at the preinvasive stage of DCIS. Therefore, FCM DNA analysis was performed on a series of ICs with predominance of DCIS. Partial or complete concordance in DNA ploidy between DCIS and IC within the individual case was found in most cases, except for the additional presence in the IC component of DNA hyperdiploid clones that might possibly be of importance for the process of invasion. In order to further characterize CIS lesions and, possibly, to discriminate biologically different groups, immunohistochemical markers were investigated in a consecutive series of CIS and IC with predominance of DCIS. The results were correlated to the histopathological and DNA ploidy findings. 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. In IC, comparison of the DCIS and the invasive component showed similar patterns. No significant differences, in neither morphology, immunohistochemistry, nor DNA ploidy, were shown between DCIS without and with invasion. These findings may indicate that none of the parameters in question may on its own be essential for the decisive event of invasive growth.
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PMID:Carcinoma in situ of the female breast. A clinico-pathological, immunohistological, and DNA ploidy study. 1287 68

PC-cell-derived growth factor (PCDGF, progranulin) is a novel autocrine growth factor that is overexpressed in human breast cancer cell lines. We have examined immunohistochemical PCDGF expression in 206 paraffin-embedded human breast lesions and investigated its association with clinicopathological variables. PCDGF staining was observed in breast carcinoma, whereas it was almost always negative in benign breast epithelium. PCDGF expression was more common in invasive ductal carcinoma (80% cases positive) than in invasive lobular carcinoma (53% positive). PCDGF staining was almost never observed in lobular carcinoma in situ. Ductal carcinoma in situ expressed PCDGF in 66% of the cases, and this expression correlated strongly with nuclear grade. Similar correlation was observed between PCDGF expression and histologic grade of invasive ductal carcinoma. Average Ki-67 index of PCDGF-negative/weakly positive invasive carcinomas (30.3) was significantly lower than that of strongly PCDGF-positive tumors (48.8, P=0.01). A larger percentage of tumors that expressed PCDGF with a staining intensity of 2+ or 3+ were p53 positive (44%) than were PCDGF-negative tumors (25%), P=0.02. PCDGF expression was independent of c-erbB-2 overexpression and of ER and PR status. Our study provides the first evidence of high incidence of PCDGF expression in human breast cancer in which it correlates with clinicopathological variables such as tumor grade, proliferation index, and p53 expression. These characteristics, as well as the virtual absence of expression in benign breast tissue, suggest an important role of PCDGF in breast cancer pathogenesis and make it a potential novel target for the treatment of breast cancer.
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PMID:Expression of PC-cell-derived growth factor in benign and malignant human breast epithelium. 1465 16

Several investigators have identified Epstein-Barr virus (EBV) particles in breast carcinomas, a fact that supports a role for EBV in mammary tumorigenesis. The possible mechanism involved in this process is not clear. The present study was carried out in an attempt to determine whether there is a relationship between latent infection with EBV and p53 and p63 expression in breast carcinomas. Immunohistochemistry developed with 3.3-diaminobenzidine tetrahydrochloride was performed in 85 formalin-fixed paraffin-embedded breast carcinomas using anti-EBV EBNA-1, anti-p63, anti-p53, anti-estrogen receptor (ER) and anti-progesterone receptor (PR) antibodies. The cases were selected to represent each of the various histologic types: intraductal carcinoma (N=12), grade I invasive ductal carcinoma (N=15), grade II invasive ductal carcinoma (N=15), grade III invasive ductal carcinoma (N=15), tubular carcinoma (N=8), lobular carcinoma (N=10), and medullary carcinoma (N=10). The ductal breast carcinomas were graded I, II and III based on the Scarff-Bloom and Richardson grading system modified by Elston and Ellis. One slide containing at least 1000 neoplastic cells was examined in each case. ER, PR, p63, p53 and EBNA-1 were positive in 60, 40, 11.8, 21.2 and 37.6% of carcinomas, respectively. There was a correlation between EBNA-1 and p63 expression (P<0.001), but not between EBNA-1 and p53 (P=0.10). These data suggest a possible role for p63 in the mammary tumorigenesis associated with Epstein-Barr virus infection.
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PMID:Does the correlation between EBNA-1 and p63 expression in breast carcinomas provide a clue to tumorigenesis in Epstein-Barr virus-related breast malignancies? 1468 49

When does proliferating breast epithelium turn malignant? Single parameter analyses have not answered this question. We have tried to answer this through an analysis of immunohistochemical staining patterns in the following morphologically defined breast lesions: atypical ductal hyperplasia (ADH, 23 cases), papilloma (12 cases), ductal cancer in situ (DCIS, 28 cases), and mammographically detected small primary cancers (34 cases). The seven antibodies used were c-neu, bcl-2, p53, p21, CD44, MIB 1, and FAS. Staining patterns were compared within groups and between groups of lesions. Interesting differences in staining patterns were seen between invasive ductal cancer and invasive lobular cancer: invasive lobular cancer was less p53-positive and more CD44-positive than invasive ductal cancer. We found no common pattern in the different proliferating epithelia to show when they become malignant.
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PMID:Expression patterns of biologic markers in small breast cancers and preneoplastic breast lesions. 1473 79

Human pre-malignant breast diseases, particularly ductal carcinoma in situ (DCIS) already display several of the aberrant phenotypes found in primary breast cancers, including chromosomal abnormalities, telomerase activity, inactivation of the p53 gene, and overexpression of some oncogenes. Efforts to model early breast carcinogenesis in human cell cultures have largely involved studies of in vitro transformation of normal finite lifespan human mammary epithelial cells (HMEC) to immortality and malignancy. We present a model of HMEC immortal transformation consistent with the known in vivo data. This model includes a recently described, presumably epigenetic process, termed conversion, which occurs in cells that have overcome stringent replicative senescence and are thus able to maintain proliferation with critically short telomeres. The conversion process involves reactivation of telomerase activity, and acquisition of good uniform growth in the absence and presence of TGFbeta. We propose that overcoming the proliferative constraints set by senescence, and undergoing conversion, represent key rate-limiting steps in human breast carcinogenesis, and occur during early stage breast cancer progression.
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PMID:Culture models of human mammary epithelial cell transformation. 1497 82


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