Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0007124 (ductal carcinoma in situ)
 3,833 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The expression of p53 protein, oestrogen receptor protein, epidermal growth factor receptor (EGFR) and overexpression of the c-erbB-2 oncoprotein was examined in a series of 149 primary symptomatic breast carcinomas. Expression of p53 was present in 62 of 146 cases (42.5%) of the invasive carcinoma and one of three cases (33.3%) of ductal carcinoma in situ (DCIS) examined. Statistical associations of tumour oestrogen receptor positivity and lack of p53 protein expression, chi 2 = 19.78 (d.f. = 1), P less than 0.001, positive tumour p53 status and poor tumour grade; chi 2 = 14.1 (d.f. = 2), P less than 0.001, EGFR expression chi 2 = 7.07, (d.f. = 1), P less than 0.01 and tumour c-erbB-2 protein overexpression; chi 2 = 4.61 (d.f. = 1), P = 0.032 were identified. Expression of p53 is rare in invasive lobular carcinoma of classical type (8.3% of cases examined) in contrast to other common types of mammary carcinoma. Non-significant trends of p53 protein expression and increased regional tumour recurrence; chi 2 = 3.20 (d.f. = 1), P = 0.074 and also poorer patient survival; chi 2 = 3.76 (d.f. = 1), P = 0.053 were identified. p53 protein expression is a common event in human breast cancer and is present in both DCIS and invasive mammary carcinoma. Abnormal expression of p53 protein is a feature of both in situ and invasive breast carcinoma, implying that the abnormal p53 protein expression may be implicated in the early stages of mammary carcinoma progression.
 ...
PMID:p53 protein expression in human breast carcinoma: relationship to expression of epidermal growth factor receptor, c-erbB-2 protein overexpression, and oestrogen receptor. 135 62

A cDNA library constructed from mRNA from a human breast carcinoma metastasis was screened with a polyclonal antibody to deglycosylated human milk fat globule membrane, resulting in the isolation of eight clones from a total of 10(5) plaques. One of these (J16) was identified as lactoferrin. It was highly expressed (as a 2.5 Kb mRNA) in lactating breast and in both normal resting tissue taken from adjacent to carcinoma or from reduction mammoplasties. Immunoreactive lactoferrin was localised to ductal cells and their secretions in both normal and mildly hyperplastic ducts. In a normal tissue screen J16 was highly expressed in stomach, poorly in skin and lymphocytes and absent from other organs examined. It was variably expressed in 33/59 invasive primary breast tumours; lactoferrin protein in these was heterogeneously distributed in epithelial tumour foci. Presence of J16 was inversely related to expression of oestrogen receptor protein (P = 0.0001). There was no significant relationship to other clinical parameters. We also found immunoreactivity in 20/41 (49%) cases of ductal carcinoma in situ. Expression was not observed in any breast or gastric cell line examined. Thus lactoferrin appears to be down regulated in some forms of cancer. The presence of lactoferrin could be a contraindication for effective endocrine therapy.
 ...
PMID:Isolation of a lactoferrin cDNA clone and its expression in human breast cancer. 173 38

The expression of the neu oncogene product was investigated in invasive and non-invasive ductal carcinomas of the breast, non-neoplastic lesions of the breast, fragments of normal adult and fetal breasts and in several other normal and fetal tissues at different weeks of pregnancy by means of an immunohistochemical study with monoclonal antibodies. The staining pattern along the cytoplasmic membrane was specific for malignancy and occurred in 29% of the breast carcinomas. It was observed in invasive carcinomas as well as in ductal carcinoma in situ and it showed a significantly higher expression in premenopausal women than in postmenopausal women. This higher expression was also present in oestrogen receptor-negative tumours. The tubules of the fetal and adult kidney, the absorption cells of the fetal and adult small and large intestine, the sebaceous glands of the fetal and adult small and large intestine, the sebaceous glands of the fetal and adult skin, the adult endocervix, the endometrium, the C-cells of the thyroid, hepatocytes and all ductal cells of the fetal breast showed a constant diffuse intracytoplasmic granular staining. staining. The same granular intracytoplasmic staining pattern was focally observed in rare cases of normal breast tissue in adults and in some cases of epitheliosis, aprocrine metaplasia and some breast carcinoma cells, which did not express neu oncogene product on their membrane. Western blot experiments showed that the cytoplasmic protein had a molecular weight of 155 kD (kilodaltons); the membrane protein is the known 185 kD neu protein.
 ...
PMID:The expression of the neu oncogene product in breast lesions and in normal fetal and adult human tissues. 257 31

The expression of oestrogen receptor protein (ER) was examined in 151 cases of symptomatic or screening detected pure ductal carcinoma in situ (DCIS) of the breast by immunocytochemical assay (ERICA), in formalin-fixed paraffin-embedded tissue, with the monoclonal antibody H 222 (Abbott). Forty-eight tumours (31.8%) of cases were ER positive. Twenty-seven (17.9%) of cases showed high level ER expression and 21 (13.9%) of cases showed low level ER immunoreactivity. Significant associations of positive tumour ER immunoreactivity and non-comedo architecture chi 2 = 6.76; (d.f. = 1): P < 0.001, small cell size chi 2 = 4.49; (d.f. = 1): P = 0.034, higher S-phase fraction chi 2 = 4.71; (d.f. = 1): P = 0.03 and lack of c-erbB-2 protein overexpression chi 2 = 7.96; (d.f. = 1): P < 0.01 were identified. No significant associations of ER expression and patient age, histological grade of necrosis in DCIS, or DNA ploidy were found. ER expression is detectable in less than one third of symptomatic and screening detected cases of DCIS, implying that endocrine therapy of DCIS may be a more appropriate form of management for morphological subtypes of DCIS which show higher rates of oestrogen receptor expression, particularly those of non-comedo and small cell type.
 ...
PMID:Oestrogen receptor expression in ductal carcinoma in situ of the breast: relationship to flow cytometric analysis of DNA and expression of the c-erbB-2 oncoprotein. 810 Apr 43

The expression of oestrogen receptor (ER) protein in invasive carcinoma of the breast and its clinical significance has been extensively evaluated. Little information is available regarding ER expression in ductal carcinoma in situ (DCIS). In this study, 46 formalin-fixed, paraffin-embedded tissue specimens of mammographically detected DCIS were evaluated immunohistochemically for the presence of ER using specific monoclonal antibodies against ER (ER-ICA Abbott Lab). The associations between ER expression and histological type, degree of differentiation and patient menopausal status were evaluated. Positive ER staining was present in 72% of cases. Non-comedo types of DCIS were more frequently ER-positive than comedocarcinoma. ER-positive tumours were inversely correlated with the presence of nuclear pleomorphism. The incidence of ER in pre-menopausal and post-menopausal women was similar. In conclusion, ER expression is present in a considerable percentage of DCIS, and ER-positivity is associated with the degree of differentiation and non-comedo carcinoma variants.
 ...
PMID:Immunohistochemical detection of oestrogen receptors in ductal carcinoma in situ of the breast. 900 43

We have used polymerase chain reaction (PCR) analysis to study the incidence of allelic imbalance at four polymorphic microsatellite markers on chromosome 6q25.1-27, three dinucleotide repeats and one trinucleotide repeat, for microdissected tumour foci from a group of 75 'early' breast carcinomas. The tumours comprised 16 preinvasive cases of ductal carcinoma in situ (DCIS) and 59 mammographically detected early invasive carcinomas. Loss of heterozygosity (LOH) was detected at all four loci and in all types and grade of disease. The frequency of LOH ranged from 23% to 50% depending on the marker studied. The highest frequency of LOH was observed at the D6S186 locus for the cases of DCIS and at the oestrogen receptor locus for the invasive carcinomas. These data suggest that the inactivation of tumour-suppressor genes within this region on chromosome 6q is important for the development of these early lesions.
 ...
PMID:Loss of heterozygosity at chromosome 6q in preinvasive and early invasive breast carcinomas. 915 53

Cyclin E is a G1 cyclin that is essential for the transition from G1 to S phase in the cell cycle. Alterations to cyclin E expression or regulation could be important in tumorigenesis. Previous immunohistochemical and immunoblotting studies have investigated the expression of cyclin E in breast carcinomas. In this study, cyclin E has been investigated in a range of non-malignant and malignant breast using immunohistochemistry. Normal and benign tissue from pre- and post-menopausal women (39 cases), non-involved tissue from cancer-containing breasts (47 cases), ductal carcinoma in situ (22 cases) and invasive breast carcinomas (109 cases) have been examined. There was no reactivity in any of the non-malignant breast. Only one ductal carcinoma in situ contained more than 5% reactive cells. A total of 28% of invasive carcinomas had > 5% of reactive cells (range 0-88% positive cells, mean 12.59%, median 1.0%). A significant association was found with poorer differentiation (P < 0.001), high MIB1 index (P < 0.001), lack of oestrogen receptor (0.05 > P > 0.025) and the presence of p53 protein (0.05 > P > 0.025). Virtually all cases with cyclin E and p53 were poorly differentiated. The presence of cyclin E is therefore only found in breast malignancies and is associated with more aggressive features, including high proliferation.
 ...
PMID:Lack of cyclin E immunoreactivity in non-malignant breast and association with proliferation in breast cancer. 937 73

Insulin-like growth factors (IGFs) play an important role in normal cellular growth and development and have been implicated in the regulation of tumour growth. Two receptors are recognized, IGFR-1 and IGFR-2, of which one, IGFR-1, is a transmembrane heterodimer structurally similar to the insulin receptor. Studies using ligand-binding assays have suggested that the proportion of human breast carcinomas expressing IGFR-1 varies between 39 and 93 per cent and all suggest a lower level of IGFR-1 expression in benign mammary epithelia. As there is this variation between studies and since no study appears to have examined the immunohistochemical localization of IGFR-1 within breast tissue, a series of 79 infiltrating ductal carcinomas, 11 infiltrating lobular carcinomas, three cases of pure ductal carcinoma in situ (DCIS), seven fibroadenomas, and eight normal breast specimens have been studied utilizing the monoclonal antibody alpha IR3. IGFR-1 localized to the epithelial component of 90 per cent of the carcinomas, with only cytoplasmic (21 per cent), only membrane (5 per cent), or a mixture of both cytoplasmic and membrane (64 per cent) staining patterns. In some tumours, distinct basolateral distribution of the receptor was observed. Invasive lobular carcinoma showed significantly less labelling than ductal (P = 0.0009). There was a significant correlation between the level of IGFR-1 immunostaining with both oestrogen receptor (P < 0.001) and progesterone receptor (P = 0.0018) positivity within the malignant group. All normal mammary epithelium showed strong labelling, which was often at an intensity matching that of the most strongly labelled carcinoma and occasionally visualized as basolateral staining of the luminal cells. Weak to moderate staining of endothelial cells was also observed. It is concluded that IGFR-1 immunoreactivity is found in the majority of breast carcinomas, where it correlates most closely with oestrogen receptor status. The high intensity labelling of normal cells seen in this study contrasts with the low levels inferred from ligand-binding-based techniques and emphasizes the importance of the morphological approach in the investigation of novel molecules.
 ...
PMID:The localization of the insulin-like growth factor receptor 1 (IGFR-1) in benign and malignant breast tissue. 949 57

Experimental studies suggest that cyclin D1 is a potential oncogene but in clinical studies of invasive breast cancer, overexpression of cyclin D1 is found to be associated with oestrogen receptor (ER) expression and low histological grade, both markers of good prognosis. Immunohistochemistry has been used to examine the relationship between cyclin D1 expression and differentiation in 36 cases of ductal carcinoma in situ (DCIS) and the interrelationship between expression of cyclin D1, its associated protein product of the retinoblastoma gene (pRb), and ER, in this group of cases. The expression of these markers has also been examined in nine cases of atypical ductal hyperplasia (ADH) and these results have been compared with the levels of expression seen in DCIS. Cyclin D1 overexpression was found in 23/36 (64 per cent) cases of DCIS and, in contrast to invasive carcinoma, there was no relationship with either differentiation or ER expression. The level of pRb expression was significantly associated with cyclin D1 expression (rS = 0.49, P = 0.001) and only two cases (6 per cent) were pRb-negative. There was no association between pRb and differentiation of DCIS or ER status. In contrast to DCIS, only one case of ADH showed overexpression of cyclin D1 (Mann-Whitney U-test, P = 0.02). All cases of ADH were ER-positive and showed moderate pRb staining, similar to that seen in well-differentiated DCIS. These results provide further evidence that overexpression of cyclin D1 plays a role early in carcinogenesis.
 ...
PMID:Cyclin D1 and associated proteins in mammary ductal carcinoma in situ and atypical ductal hyperplasia. 966 5

Following breast-conserving surgery for ductal carcinoma in situ (DCIS), the presence of comedo necrosis reportedly predicts for higher rates of post-operative recurrence. To examine the role of programmed cell death (apoptosis) in the aetiology of the cell death described as comedo necrosis, we studied 58 DCIS samples, using light microscopy, for morphological evidence of apoptotic cell death. The percentage of apoptotic cells (apoptotic index, AI) was compared between DCIS with and without evidence of 'comedo necrosis' and related to the immunohistochemical expression of the anti-apoptosis gene bcl-2, mitotic index (MI), the cellular proliferation antigen Ki67, nuclear grade and oestrogen receptor (ER) status. AI was significantly higher in DCIS samples displaying high-grade comedo necrosis than in low-grade non-comedo samples: median AI = 1.60% (range 0.84-2.89%) and 0.45% (0.1-1.31%) respectively (P < 0.001). Increasing nuclear grade correlated positively with AI (P < 0.001) and negatively with bcl-2 expression (P = 0.003). Bcl-2 correlated negatively with AI (P = 0.019) and strongly with ER immunoreactivity (P < 0.001). Cellular proliferation markers (MI and Ki67 immunostaining) correlated strongly with AI and were higher in comedo lesions and tumours of high nuclear grade (P < 0.001 in all cases). Thus, apoptosis contributes significantly to the cell death described in ER-negative, high-grade DCIS in which a high proliferative rate is associated with a high apoptotic rate. It is likely that dysregulation of proliferation/apoptosis control mechanisms accounts for the more malignant features typical of ER negative comedo DCIS.
 ...
PMID:Evidence of significant apoptosis in poorly differentiated ductal carcinoma in situ of the breast. 974 2


1 2 3 4 5 6 Next >>