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)

Using permanent-section immunohistochemistry, we investigated the role of HER-2/neu in the development and progression of human breast cancer by measuring its overexpression in a series of hyperplastic (n = 30), dysplastic (n = 15), and malignant neoplastic (n = 708) lesions of ductal epithelium and by evaluating the relationships between overexpression and clinicopathologic features known to have prognostic significance in these lesions. The neoplasms included pure ductal carcinoma in situ (DCIS; n = 59) and infiltrating ductal carcinoma (IDC; n = 649). The latter were all node negative and stratified into IDC combined (n = 237) or not combined (n = 412) with a "significant amount" of DCIS (defined as DCIS greater than or equal to 10% of total tumor cellularity). Overexpression of HER-2/neu was not observed in any of the hyperplastic or dysplastic lesions. In contrast, it was present in 56% of pure DCIS and in 77% of the comedo subtype of this group. Only 15% of IDC overexpressed HER-2/neu. However, the rate of overexpression was significantly higher in the subset of IDC combined with DCIS compared with the subset of IDC not combined with DCIS (22% v 11%, respectively; P less than .0001). These results are consistent with the hypothesis that HER-2/neu plays a more important role in initiation than in progression of ductal carcinomas. They also suggest that overexpression decreases within individual tumors as they evolve from in situ to increasingly invasive lesions or, alternatively, that many invasive carcinomas arise de novo (ie, without progressing through a significant in situ stage) by mechanisms not involving HER-2/neu. In addition, overexpression of HER-2/neu was associated with several poor prognostic features (younger patient age, premenopause, negative estrogen receptor status, negative progesterone receptor status, and high nuclear grade) in the subset of IDC combined with DCIS. With one exception (negative estrogen receptor status) these associations were lost in IDC not combined with DCIS, also suggesting that the role of HER-2/neu changes during the progression of human breast cancer.
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PMID:Overexpression of HER-2/neu and its relationship with other prognostic factors change during the progression of in situ to invasive breast cancer. 135 64

Her-2/neu protein product was immunocytochemically analyzed in 139 breast cancers. Epidermal growth factor receptors were similarly analyzed in 74 breast cancers from the same patient pool. These results were also separated on the basis of estrogen receptor proteins and of combined aneuploidy with elevated S-phase from flow cytometry. Invasive breast cancer yielded a positive label for Her-2/neu protein (26%) and for epidermal growth factor receptor (25%), with no significant difference. Correlations with estrogen receptor labeling yielded differences significant inversely for both Her-2/neu protein (p less than 0.02) and epidermal growth factor receptor (p less than 0.01). Positive Her-2/neu protein labels correlated with a positive combination of aneuploidy and elevated S-phase (37%) and a negative combination of aneuploidy and elevated S-phase (21%), with a statistically nonsignificant difference. Positive epidermal growth factor receptor cases with aneuploidy and an elevated S-phase (75%) and without aneuploidy and elevated S-phase (42%) did differ with significance at p less than 0.05. There were eight cases positive for both Her-2/neu protein and epidermal growth factor receptor, four of six cases with negative estrogen receptor, four of six cases with negative estrogen receptor, six of six cases aneuploid, and five of six cases with an elevated S-phase. All eight cases had threatening disease--either stage III or stage IV, with one case of extensive ductal carcinoma in situ (comedo). Correlation of negative Her-2/neu protein with negative epidermal growth factor receptor was significant (p less than 0.05) in 74 cases. However, positive Her-2/neu protein did not correlate with positive epidermal growth factor receptor; there was a trend toward inverse correlation. We conclude that epidermal growth factor receptor labeling results show similarities to Her-2/neu protein results, but epidermal growth factor receptor tended to correlate with unfavorable ploidy and S-phase. Epidermal growth factor receptor labeling might be useful in breast cancers with macrocysts reported to show high epidermal growth factor activity.
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PMID:Expression of Her-2/neu oncogene protein product and epidermal growth factor receptors in surgical specimens of human breast cancers. 167 11

A number of investigators have suggested treatment of precursor lesions for invasive breast cancer such as ductal carcinoma in situ with antiestrogen. However, very little information is available on the incidence of estrogen receptor in such lesions and the probability of treatment success. Fourteen formalin-fixed tissue specimens of intraductal carcinoma in situ from 14 female patients aged 40 to 66 years were evaluated for the presence of estrogen receptor by immunoperoxidase technique using estrogen receptor antibody. Eight of the 14 lesions (57%) were positive for estrogen receptor. The incidence of estrogen receptor in intraductal carcinoma in situ is very similar to that of invasive carcinoma of breast, leading to the speculation that ER-positive invasive carcinoma originates from ER-positive precursor lesions. Since only 70 per cent of positive receptor lesions are expected to respond to antiestrogens, it appears that only 40 per cent of patients with ductal carcinoma in situ of breast will benefit from endocrine therapy.
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PMID:Estrogen receptors in ductal carcinoma in situ of breast. 216 37

Between 1978 and 1985, 393 of 2,765 (14%) patients with operable cancer of the breast (clinical stage T0-3N0-2M0) were irradiated after excisional biopsy and staging axillary dissection. Of 77 patients with microscopic axillary metastases, 68 received systemic adjuvant therapy. Treatment failed locally in 26 cases, and there were seven patients with distant metastasis. The three major factors for increased local treatment failure were (a) age below 40 years (P = .003), (b) negative estrogen receptor assay result (P = .03), and (c) failure to deliver a radiation boost dose when tumor was present at the margin of the specimen (P = .002). The size of the tumor, the nodal status, the progesterone receptor assay result, and the presence of ductal carcinoma in situ mixed with infiltrating carcinoma did not show a significant influence on local recurrence. In 274 of 393 (70%) patients, cosmesis was evaluated. The four major factors affecting cosmesis favorably were (a) utilization of a wedge (P less than .0001); (b) treatment of two fields a day (P less than .0001); (c) failure to use a separate treatment port to the regional lymph nodes, so as to avoid field junctions (P = .0003); and (d) small size of specimen (less than 50 cm2) (P = .0171). A second or third cancer was found in 39 of the 393 (10%) patients; contralateral breast cancer was the most common form (n = 23), followed by genitourinary cancer (n = 5). The most frequent complication was arm edema (6%).
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PMID:Prognostic factors for recurrence and cosmesis in 393 patients after radiation therapy for early mammary carcinoma. 254 75

A retrospective immunoperoxidase staining study for a glycoprotein isolated from human breast gross cystic disease fluid (GCDFP-15) in 562 primary breast carcinomas in 539 patients was conducted to correlate its immunohistochemistry with pathologic and clinical factors. Overall, 55% of the carcinomas studied stained positively for GCDFP-15. In certain histologic subtypes, the percentage of carcinomas that stained positively was greater: those subtypes with apocrine histologic features (75%), intraductal carcinoma (70%), and infiltrating lobular carcinoma with signet-ring cell differentiation (90%). In contrast, only 5% of medullary carcinomas exhibited positive staining. Only 23% of breast carcinomas without apocrine features stained positively for GCDFP-15. Carcinomas that stained positively were more likely to have involved axillary lymph nodes (P less than 0.054). The staining was independent of nuclear grade, mitotic index, tumor size, and estrogen receptor status. Positive staining was related to a history of gross cystic disease but not to age, parity, menopausal status, or age at first birth. A positive stain was not related to risk of recurrence or survival.
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PMID:Expression of GCDFP-15 in breast carcinomas. Relationship to pathologic and clinical factors. 265 63

Several investigators, the SEER data, and the ECOG/Intergroup study have shown that patients with small tumors (< 0.5 cm) have a recurrence rate of less than 2%, compared to 20-25% for large tumors (> or = 5 cm). Nuclear grade and tumor differentiation are established indicators; however, the interobserver lack of concordance has thwarted their use in clinical trials. The presence of peritumoral lymphatic and blood vessel invasion (PLBI) is associated with a relative risk of recurrence of 4.7. The predictive value of the presence of hormone receptors in tumors is associated with a favorable disease free and overall survival difference of 8-10%; however, this advantage is being eroded by the early appearance of other factors, such as the epidermal growth factor receptor (EGFR), proliferative capacity (S-phase), nuclear grade, and HER-2/neu oncogene. Concordance among the different methods of hormone-receptor assay (immunocytochemical, sucrose gradient, and dextran-coated charcoal) is essential to refine the true value of these factors. DNA flow cytometry measurements of ploidy (DNA content) and S-phase fraction are the most characterized of the prognostic factors. There are conflicting reports regarding the clinical significance of ploidy status, while measurements of S-phase fraction clearly indicate a robust association with disease free and overall survival. Our data continue to show that S-phase, but not ploidy, can predict time to recurrence significantly in untreated patients, even when data are stratified for tumor size. HER-2/neu oncogene is expressed in about 50% of ductal carcinoma in situ and 14% of invasive ductal carcinoma. The presence of this oncogene at high copy number may be a useful independent marker of poor prognosis and may be associated with drug resistance and correlated with tumor recurrence and shorter survival. EGFR could be measured in most breast tumors, and the level of its expression has inversely correlated with estrogen receptor protein expression. The value of EGFR as a predictor of prognosis remains controversial and is still being investigated. Cathepsin-D provides a provocative biologic rationale but is hindered by different and incongruent methods of analysis. The majority of large studies with more than 3-years' follow-up suggests that high cathepsin-D levels may be predictive of greater recurrence and lower survival. Angiogenesis has been implicated as a critical component of the metastatic process. Early studies show that tumor angiogenesis is an independent and highly significant prognostic indicator, and its presence may suggest the selection of "anti-angiogenic therapy."(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Prognostic factors in early breast carcinoma. 800 12

A total of 8 major adjuvant trials are today open for entry in Sweden excluding trials conducted by international research groups with Swedish collaboration. The yearly accrual rate is about 1,600 patients. The randomized comparisons are: (1) tamoxifen 2 years versus 5 years in postmenopausal stage I-II patients, (2) sequential tamoxifen/megestrol in alternating 3 months cycles for 2 years versus tamoxifen alone for 2 years in estrogen receptor (ER)-positive, postmenopausal stage I-II patients, (3) tamoxifen for 2 years versus tamoxifen+LHRH-analogue for 2 years versus LHRH-analogue alone versus control in premenopausal stage I-II patients, (4) CMF chemotherapy versus radiological castration in ER-positive, premenopausal stage II patients, (5) high-dose chemotherapy+autologous bone marrow transplantation versus conventional chemotherapy in high-risk (pN6+) stage II patients aged under 60 years, (6) postoperative radiotherapy to the breast versus control after breast-conserving surgery for invasive stage I-II breast cancer, (7) postoperative radiotherapy to the breast versus control after breast-conserving surgery for ductal carcinoma in situ (DCIS), and (8) CMF- or FEC-chemotherapy plus APD (pamidronate) versus the same chemotherapy without APD. Current plans for future trials include in vivo monitoring of treatment response, that is, the change in the proportion of proliferating tumor cells, during neo-adjuvant chemotherapy.
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PMID:Randomized adjuvant breast cancer trials in Sweden. 803 52

The immunohistochemical expression of the p53 gene protein was examined in a consecutive series of 143 cases of pure ductal carcinoma in situ (DCIS) of the breast. Expression of wild-type and/or mutant p53 protein was detected in 36 (25.2%) of the cases examined, as evidenced by positive nuclear staining with the monoclonal antibody DO 7. Thirty-four (35.8%) of the large cell cases showed p53 protein expression compared with two (4.1%) of the small cell cases (chi 2 = 15.3 [df = 1], P < .001). p53 Protein expression also was associated with an increased histologic degree of necrosis, with a nearly significant association of negative tumor estrogen receptor status and p53 protein expression. No significant association of p53 protein expression and c-erbB-2 protein expression was seen. Immunohistochemical expression of p53 protein is present in approximately 25% of DCIS cases and is confined almost exclusively to large cell DCIS, a morphologic subtype of in situ breast carcinoma thought to be more biologically aggressive. Expression of p53 protein may be important in the neoplastic progression of DCIS, reflecting the acquisition of p53 gene mutations in large cell DCIS cases. Therefore, p53 may be implicated in mammary tumor evolution from in situ to invasive disease.
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PMID:p53 protein expression in mammary ductal carcinoma in situ: relationship to immunohistochemical expression of estrogen receptor and c-erbB-2 protein. 809 18

The expression of pS2 was examined histochemically in paraffin sections taken from biopsy material from patients diagnosed with ductal carcinoma in situ (DCIS). Often intense immunoreactivity, to an anti-pS2 monoclonal antibody, was observed in comedo, solid, cribriform and micropapillary types of DCIS, with significant positivity found in 63-67% of cases. In 15 samples analysed, we found a good correlation between pS2 expression and presence of progesterone receptor positive cells, but not with estrogen receptor. There was only a limited degree of correspondence between the cells staining with these anti-sera. Some pS2 positive cells were also seen in normal acini in areas adjacent to cancer but much less frequently in sections of normal breast from reduction mammoplasty. Most normal areas were negative, as were cysts. In benign proliferative conditions (seen in sections with and without DCIS) such as adenosis, sclerosing adenosis, mild and florid ductal epithelial hyperplasia, significant pS2 positivity was seen in about 50% of cases. These results suggest that there is a progressive increase in pS2 from normal to benign to cancer cells and that this gene is expressed in both the invasive and pre-invasive forms of breast cancer.
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PMID:Immunohistochemical localisation of pS2 protein in ductal carcinoma in situ and benign lesions of the breast. 838 77

Multiple sections of 40 consecutive cases with invasive ductal carcinoma of the breast, all of which bad wide intraductal cancerous extension, were examined by immunohistochemical analysis for evaluation of hormone dependency in several areas of breast cancer tissues. In this study, we examined the expression of pS2 protein in the central invasive area (CIV), central intraductal cancerous area (CDC) and forefront intraductal cancerous area (FDC). pS2 staining was positive in 52.5% (21/40) of CIV and a significant correlation was found between pS2 expression in CIV and the estrogen receptor status (ER). pS2 staining was positive in 77.5% of CDC and 85.0% of FDC, respectively. A majority (68.4%) of the cases that were negative pS2 in CIV were positive for pS2 in FDC. Moreover, the cases with noncomedo intraductal carcinoma in premenopausal status showed a higher positivity of pS2 expression in FDC than the cases with comedo-carcinoma, though the number of cases of comedo-carcinoma was limited. These findings suggest that endocrine therapy may be useful after breast conserving treatment regardless of the ER status of the primary tumor.
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PMID:High positive rate of pS2 expression in forefront intraductal cancerous area in breast cancer. 856 93


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