Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0677930 (primary tumor)
 20,210 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The protein p53 is a product of a suppressor oncogene. Mutations occurring in 13-15% of breast carcinomas are associated with p53 stainability within nuclei and progression of the tumor. We determined the extent to which p53 abnormality was associated with proliferation by measuring p53 immunohistochemically with a polyclonal antibody and monoclonal PAb1801 in invasive carcinomas of known S-phase fraction (SPF) assessed histologically by bromodeoxyuridine incorporation. Results with the two antibodies always agreed. One of 20 low, 2/18 midrange, and 9/17 high SPF carcinomas were positive for p53. P53 positivity was also related to other indicators of aggressiveness including size of primary tumor, nuclear and nucleolar size, and estrogen and progesterone receptor content, but relationships between p53 and vascular invasion and lymph node metastasis were not found. We conclude that nuclear p53 accumulation is more closely related to proliferation than to invasion and metastasis, and that it identifies some but not all breast carcinomas with high proliferative indices.
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PMID:High proliferative rates demonstrated by bromodeoxyuridine labeling index in breast carcinomas with p53 overexpression. 802 44

Estrogen and progesterone receptor concentrations were measured in the primary tumors of 137 surgically staged women with clinical stages I and II endometrial carcinoma. For each steroid, increasing receptor concentrations were associated with a decrease in hazard (increase in survival) and the effect was linear for each receptor. When expressed dichotomously, steroid receptor status was also significantly associated with a number of known risk factors, and the significance of the association was influenced by the receptor concentration used as the criterion for receptor positivity. In a multivariate analysis, only progesterone receptor concentration affected survival independently, but the effect disappeared when the analysis was restricted to women with disease confined to the uterus. We conclude that the estrogen and progesterone receptor status of the primary tumor is of limited prognostic significance in endometrial carcinoma unless extrauterine disease is present.
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PMID:Steroid receptor concentrations in endometrial carcinoma: effect on survival in surgically staged patients. 840 87

The steroid receptor content in breast carcinoma correlates with the responsiveness of malignant cells to endocrine manipulation. Although the steroid receptor status of the primary tumor is mostly used to select systemic therapy, it was suggested that steroid receptor content should be evaluated in metastatic lesions whenever possible. In this study the estrogen and progesterone receptor content was determined biochemically in 38 pleural effusions from advanced breast cancer patients. In 17/38 patients the steroid receptor status was assessed twice during the course of the disease - at diagnosis in the primary tumor/lymph nodes, and subsequently in metastatic pleural effusion fluid. A trend towards lower receptor values in pleural fluids was evident. There was no correlation between pleural steroid receptor content and pleural response to endocrine or chemo/endocrine therapy, indicating that the usefulness of effusional steroid receptors for therapy planning of advanced breast cancer could not be confirmed in this study.
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PMID:Steroid receptors in pleural effusions of advanced breast cancer patients. 855 Oct 56

The role of molecular markers predicting the response to cytotoxic chemotherapy is not established. A potential predictive factor, topoisomerase IIalpha, is a target for certain cytotoxic drugs, and its concentration has been shown to correlate with chemosensitivity in vitro. We evaluated expression of topo IIalpha immunohistochemically in 230 breast cancer samples and studied its association with known clinicopathological factors and factors previously shown to predict response to cytotoxic drugs. Topo IIalpha protein expression was found in 0.6 to 39.4% (10.6 +/- 7.9%, mean +/- SD) of breast carcinoma cells, whereas expression was undetectable in nonmalignant breast epithelium. Topo IIalpha protein expression correlated well with semi-quantitative mRNA in situ hybridization (P = 0.007). A significant association was found between the proportion of topo-IIalpha-positive cells and low estrogen and progesterone receptor content (P<0.0001), high grade (P<0.0001), DNA aneuploidy (P=0.003), and c-erbB-2 oncoprotein overexpression (P<0.0001). Topo IIalpha expression was not associated with clinical variables, such as age of the patient, primary tumor size, or axillary nodal status. A highly significant linear correlation was found between topo IIalpha and tumor proliferation rate (S-phase fraction, r=0.46; P<0.0001). Because hormone receptors, grade, and ploidy are associated with tumor proliferation rate, topo IIalpha expression was adjusted for S-phase fraction to reveal the proliferation-independent clinopathological associations. According to the analysis of co-variance, only aneuploidy (P=0.0003) and c-erb-2 overexpression (P=0.01) were associated with proliferation-adjusted expression of topo IIalpha. In conclusion, the close association of Topo IIalpha with other potential predictive factors (tumor proliferation rate, c-erbB-2 oncoprotein) suggests that topo IIalpha, having a defined role as a target for cytotoxic drugs, may be a valuable predictor of response to chemotherapy.
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PMID:Expression of topoisomerase IIalpha is associated with rapid cell proliferation, aneuploidy, and c-erbB2 overexpression in breast cancer. 866 91

The prognostic value of epidermal growth factor receptor (EGFR) expression and its biological role in estrogen receptor-positive (ER+) and ER-negative (ER-) primary breast cancer is controversial. In this study, distributions of ER, progesterone receptor and EGFR have been established using immunohistochemistry in both primary breast tumors and their matched axillary lymph node metastases of 26 patients or their matched distant metastases of 2 patients. In addition, 5 patients with bilateral breast cancer were studied. ER+ tumor cells were detected in 22 (69%) and EGFR+ tumor cells were detected in 11 (34%) primary breast carcinomas. Expression of ER and EGFR was inverse regarding the individual tumor cells in both primary tumors and metastases. Relationship of EGFR expression with poorly differentiated and large breast tumors was observed. Furthermore, primary tumors with a predominant lobular component were ER+ and, with one exception, EGFR-. Invasive ductal carcinomas were more frequently EGFR+. No apparent differences in receptor expression were observed between primary tumors and lymph node metastases or chronously or metachronously occurring bilateral breast cancers. Only one ER+ primary tumor showed a switch to EGFR expression in the involved lymph node. Our study shows that a shift in receptor phenotype between primary tumors and lymph node metastases is a rare event and, thus, additional analyses of involved lymph nodes will not likely serve as a better predictor for response to anti-estrogen therapy. We conclude that expression of EGFR is not a prerequisite for development of metastases.
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PMID:Expression of estrogen, progesterone and epidermal growth factor receptors in primary and metastatic breast cancer. 884 35

Proliferative activity was studied by immunohistological assay of label index (LI) involving the injection of 5-bromo-2'-deoxyuridine in vivo into 10 benign lesions and 40 breast tumors. LI level was found to be significantly higher in breast cancer patients (10.94%) than in cases of benign lesions (1.97%) (p = 0.000002). A similar relation was recorded between relapsed breast cancer (16.65%) and primary tumor (10.28%) (p = 0.03). The study also established a distinct correlation between LI of invasive ductal carcinoma and histological malignancy as determined according to Bloom and Richardson, p = 0.045 between stages I (6.03%) and II (9.60%) and p = 0.01 between stages II and III (15.37%), the ability to form tubular structures (p = 0.003), the numbers of mitoses and hyperchromatic nuclei (p = 0.006) between stages I (5.95%) and II (9.53%) and p = 0.003 between stages II and III (15.00%) and presence or absence of nuclear polymorphism (p = 0.03%). No correlation was observed between LI in breast tumor, on the one hand, and tumor size, degree of invasion, clinical stage, age, menstrual status and estrogen and progesterone receptor levels, on the other. LI in metastasis (7.07%) (15 cases) appeared to be significantly higher than in primary tumor (10.13%) (p = 0.001) and it revealed a distinct correlation with that in primary tumor (p = 0.39).
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PMID:[Determination of the proliferative activity of breast cancer cells using 5-bromo-2'-deoxyuridine in vivo]. 921 18

We have analyzed serum levels of soluble HER-2/neu in 42 primary breast cancer patients prior to any therapy and studied the relationship between the overexpression and amplification of HER-2/neu in the primary tumor after surgical excision and data obtained by pathohistological staging. In addition, we have investigated the sera of 62 patients with stage IV breast cancer. Using an enzyme-linked immunosorbent assay, we observed elevated serum HER-2/neu levels in 6/42 (14.2%) preoperative patients. In 42.8% of the patients with HER-2/neu tumor expression/amplification serum levels were increased. In contrast, only 8.5% of the patients without HER-2/neu expression/amplification in the primary tumor presented with elevated serum levels. There was a significant correlation between serum concentrations of soluble HER-2/neu and tumor size (p < 0.0001) or axillary lymph node involvement (p < 0.0001). In patients with stage IV disease, 27 of 62 (43.5%) had elevated soluble HER-2/neu serum levels. A highly significant correlation between soluble HER-2/ neu and CA 15-3 (p < 0.002) was observed. The correlation of serum concentrations of HER-2/neu with estrogen and progesterone receptor status of the primary tumor was not significant in both groups. In conclusion, the measurement of serum HER-2/neu levels at diagnosis defines a small subgroup of breast cancer patients with a relatively advanced stage of disease. Its strong correlation with tumor load in patients with stage II disease and the high prevalence in patients with stage IV disease could make it a promising tool for the assessment of disease activity and biologic behavior in breast cancer.
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PMID:Tissue expression and serum levels of HER-2/neu in patients with breast cancer. 939 44

Flow-cytometric DNA analysis was performed retrospectively from paraffin-embedded blocks in 158 consecutive ductal infiltrative breast carcinoma patients grades I-III. Normal breast tissue was used as control. Tumor proliferative activity, cell ploidy, and DNA index (DI) were related to age of patients, histological grade of tumor, tumor size, axillary lymph node status, estrogen and progesterone receptor status, menopausal status,TNM clinical classification, and survival. There was a significant association between DNA aneuploidy and a high cellular proliferative activity, increased DI, poor differentiation of tumor, primary tumor size, number of positive lymph nodes, and postmenopausal state. Increased proportion of cells in S-phase was associated with positive lymph node status and higher number of positive lymph nodes. The cell cycle parameters had no prognostic value either for overall survival of disease-free survival of the patients.
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PMID:Prognostic significance of cell cycle parameters in infiltrative ductal breast carcinoma. 959 98

Prognostic factors for distant metastases in patients with local recurrence after breast-conserving treatment (BCT) were studied. Fifty-six patients who developed local recurrence after BCT were recruited from 18 key hospitals/institutes in Japan. All 10 patients whose primary tumors were DCIS fared well without evidence of distant failure for a median follow-up period of 57 months (range 41-72) after the local recurrence. Inflammatory local recurrence was observed in 5 patients whose prognosis was grave: 3 with concomitant distant metastases and 1 developing them 7 months later. In the remaining 41 patients with noninflammatory local recurrence, various clinicopathological factors including age, disease-free interval, histology of the primary and recurrent tumors, axillary lymph node status, estrogen and progesterone receptor, immunohistochemical staining of erbB2 and p53 protein were evaluated as prognostic factors. Only the p53 immunostaining status of the primary tumor was found to be a significant prognostic indicator for distant metastases; distant disease-free survival at 5 years after the local recurrence was 92% for patients with p53-negative cancers and 51% for those with p53-positive cancers (p < 0.05).
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PMID:The possible prognostic significance of p53 immunostaining status of the primary tumor in patients developing local recurrence after breast-conserving surgery. 973 24

We screened for the prognostic value of estrogen receptor (ER) and progesterone receptor (PR) through a multicentric study of 2,257 operable breast cancer patients who did not received adjuvant therapy. Three hundred and seven local-regional recurrences, 105 metachronous contralateral breast cancer, 589 metastases and 537 deaths from cancer had been diagnosed with a median follow-up of 8.5 years. A total of 69% of the tumors were ER positive and 54% PR positive. For statistical analysis, 1,665 patients were studied because of complete clinical and biological data. In univariate analysis, ER and PR status were of prognostic value for the metastases-free interval (MFI) and the overall survival (OS). In multivariate analysis (Cox proportional hazard model), only the ER status showed a significant difference between positive and negative groups regarding the MFI and OS. By using Cox regression model with time-dependent covariates, we show that the predictive value of ER status of the primary tumor decreases by approximately 20% per year, losing its significance after 8 years of follow-up. These results show that ER and PR status have a relatively limited predictive value and their major interest remain in the domain of therapeutic decision.
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PMID:[Long-term prognostic role of steroid receptors in cancer of the breast]. 975 99


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