Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0006142 (breast cancer)
 160,383 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cytospins of a human breast cancer cell line (MCF-7) were studied for the expression of PCNA, a cell cycle-related protein, using a variety of fixation and immunostaining procedures. The best fixative for PCNA was found to be buffered formaldehyde solution at 4 degrees C followed by methanol at 20 degrees C, whereas alcoholic fixatives decreased greatly the PCNA immunoreactivity. Air-drying procedures of cytospins prior to and after fixation greatly undermined the PCNA immunostaining. A modified immunoperoxidase method provided a stronger staining of the PCNA-reactive cells than the alkaline phosphatase anti-alkaline phosphatase (APAAP) technique. PCNA immunoreactivity could be maintained up to 2 mo, putting slides in methanol at -20 degrees C. In conclusion, our report indicates that PCNA is a labile antigen, which may critically be affected by temperature and air-drying procedures.
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PMID:Methodological aspects of the immunostaining of proliferating cell nuclear antigen (PCNA) in cytospin preparations of MCF-7 cell line. 791 57

The prognostic value of c-erbB-2 protein overexpression has been evaluated in 463 patients with operable breast cancer after a median follow-up of 66 months. Overexpression was observed in 99/463 (21%) of the breast tumors. It showed significant positive correlation to histological grade (p < 0.0001) and tumor size (p < 0.02). A relationship of borderline significance was observed between c-erbB-2 protein overexpression and negative or low estrogen receptor (ER) content. No significant correlation was found to lymph node involvement or proliferating tumor cell fraction as determined by the proliferating cell nuclear antigen (PCNA). After a median follow-up of 66 months (range 6 to 109 months), the overall survival of all patients amounted to 63%. Multivariate analysis revealed lymph node involvement, tumor size, histological grade, histological type, c-erbB-2 protein overexpression, progesterone receptor (PR) content, and oral contraceptive use as independent prognostic factors. In an univariate analysis, the overall survival amounted to 72% and 38% of tumor patients with negative and positive c-erbB-2 protein overexpression, respectively. The most significant finding is that c-erbB-2 overexpression has been recognized as an independent predictive factor in subsets of tumor patients who would be expected to have a generally poor prognosis, such as those indicating axillary lymph node involvement, large tumor size (> 2 cm), and PR negativity.
Breast Cancer Res Treat 1994
PMID:C-erbB-2 overexpression in primary breast cancer: independent prognostic factor in patients at high risk. 791 7

We compared immunohistochemical staining by two monoclonal antibodies, PC10 and 19A2, to standard methods for cell proliferation, 3H-TdR or BrdU labeling index (S-LI) and S-phase fraction by flow cytometry (S-flow). One hundred thirty-two breast carcinomas were studied retrospectively using formalin fixed, paraffin embedded archival tissues on which S-LI and S-flow had been obtained originally. Percentages of tumor cells positive with PC10 and 19A2 correlated well (r = 0.736, p < 0.0001), although the mean marking index for 19A2 was lower and closer to reference measurements than the mean PC10 index. Correlations between PC10 or 19A2 vs. S-LI, S-flow or DNA ploidy (DNAI) were significant in a group of 64 tumors obtained between 1988 and June 1992, and poor in another group of 68 tumors obtained between 1985 and 1988, suggesting deterioration of stainability with prolonged storage. Discrimination of faint staining from negative nuclei was difficult on PCNA stained sections. Carnoy fixation did not improve results over those fixed with formalin. S-flow and S-LI predicted relapse-free survival, but PCNA indices did not. We conclude that PC10 and 19A2 immunostaining of formalin or Carnoy fixed archival breast cancer tissue correlated with reference measures of proliferation only in cases of short storage periods. Although statistically significant, levels of correlation were too low to use PCNA indices for prognosis.
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PMID:Assessment of proliferating cell nuclear antigen (PCNA) in breast cancer using anti-PCNA PC10 and 19A2: correlation with 5-bromo-2'-deoxyuridine or tritiated thymidine labeling and flow cytometric analysis. 791 35

Sixty-five cases of invasive breast cancer < or = 1 cm. in largest diameter (pT1a-b) were studied retrospectively using immunohistochemical staining with PC10, a monoclonal antibody to proliferating cell nuclear antigen (PCNA). The percentage of PC10 positive tumor cells was closely related to histological grading. No association was found between PC10 score and nodal status. ER-ICA was performed on 42 cases and showed no correlation with PC10 staining. The clinical behaviour of these tumors was excellent, with 5-year survival rates overall of 96% (90% disease free survival), and apparently unrelated to histological type and grade, nodal involvement and hormonal receptor status. The prognostic value of PCNA labeling rates remains nuclear in breast cancer of minimal size as well as in larger ones.
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PMID:Minimal breast cancer: analysis of proliferative activity using a monoclonal antibody to proliferating cell nuclear antigen (PCNA) and its relationship to histological grade and prognosis. 793 57

In 471 breast cancer patients the possible influence of an antecedent oral contraceptive (OC) use on proliferative activity (PCNA-expression) of mammary carcinomas was investigated. PCNA-expression (Proliferating Cell Nuclear Antigen) was immunohistochemically assessed using formalin-fixed, paraffin-embedded tissue. PCNA-expression discriminated tumors of low (< 20%) and increased (> or = 20%) proliferative fractions. 297 (63%) patients had ever used OCs and 202 (43%) of them were long-term users (> or = 49 months). Age adjusted proliferative fractions showed no statistically significant differences dependent on duration of OC use (never, 1-48 months, > or = 49 months), despite a slightly higher frequency of tumors with an increased PCNA-expression in ever users of OCs (p = 0.125).
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PMID:[Effect of oral contraceptives on the proliferative activity of breast cancer]. 794 3

Regulatory sequences derived from the rat whey acidic protein gene have been used to preferentially overexpress a murine 172Arg-->Leu mutant p53 in the mammary gland of transgenic mice. Several different lines of mice expressing the 172Arg-->Leu mutant p53 displayed an impaired ability to lactate, and the mice expressing the highest levels of mutant p53 were unable to nurse their young. This failure was related to the inhibition of normal lobuloalveolar development that occurred during late pregnancy and a marked decrease in milk protein gene expression at early lactation. Interestingly, immunohistochemical analysis revealed that the mutant p53 was localized predominantly in the cytoplasm of alveolar cells. Ductal development was not overtly impaired in these mice. Expression of the 172Arg-->Leu mutant p53 resulted in radiation-induced apoptosis, and transactivation or repression of the expression of a number of genes, including mdm-2 and proliferating cell nuclear antigen, known properties of wild-type p53. The availability of lines of mice preferentially expressing specific p53 mutants in the mammary gland should facilitate evaluation of the roles of other factors, such as hormones, oncogenes and chemical carcinogens, in the etiology of breast cancer.
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PMID:Preferential overexpression of a 172Arg-->Leu mutant p53 in the mammary gland of transgenic mice results in altered lobuloalveolar development. 794 86

Proliferating cell nuclear antigen, PCNA (PC10), immunolabelling was determined in 175 women with breast carcinomas and related to other established prognostic factors: flow-cytometric data, volume-corrected mitotic index, sex steroid receptor content and clinical outcome during the mean follow-up of 9 years. The maximum fraction of PCNA-positive nuclei (PCNAmax), the average fraction of positive nuclei (PCNAtot) and the number of intensely stained nuclei per microscope field (PCNAcount) were significantly related to histological grade (P < 0.001), DNA ploidy ((P < 0.001), S-phase fraction (P < 0.001), mitotic index (P < 0.001) and sex steroid receptor content (P = 0.002). PCNAmax (P = 0.015) predicted survival in univariate analysis; PCNAtot (P = 0.025), PCNAmax (P = 0.007) and PCNAcount (P = 0.019) predicted the recurrence-free survival. In axillary-lymph-node-negative tumours, PCNAtot (P = 0.092), PCNAmax (P = 0.036) and PCNAcount (P = 0.006) predicted survival and recurrence-free survival (P = 0.011), (P = 0.012) and (P = 0.006) respectively. In multivariate analysis including clinical, histological, flow-cytometric and biochemical variables, PCNAtot (P = 0.004) predicted the recurrence-free survival independently. In axillary-lymph-node-negative breast cancers, PCNAtot predicted accurately the patient survival (P = 0.002) and the recurrence-free survival (P = 0.002). The results indicate that PCNA immunolabelling has independent prognostic value particularly in local breast cancer.
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PMID:Proliferating-cell nuclear antigen (PC10) immunolabelling and other proliferation indices as prognostic factors in breast cancer. 809 51

The fraction of nuclei positive for proliferating cell nuclear antigen (PCNA) was determined in 205 axillary lymph node negative (pN-) breast carcinoma. The results were related to established prognostic factors and prognosis during the mean follow-up period of 11 years. The maximum fraction of PCNA-positive nuclei (PCNAmax), the average fraction of positive nuclei (PCNAtot) and the number of intensively stained nuclei/microscope field (PCNAcount) were significantly related to histological grade (p < 0.001), DNA Ploidy (p < 0.022), S phase fraction (p < 0.003) and mitotic index (p < 0.003). PCNAmax (p = 0.020) and PCNAcount (p < 0.003) predicted recurrence-free survival in univariate analysis whereas tumour diameter (p < 0.001) was an independent predictor in a multivariate analysis. In univariate survival analysis PCNAtot (p < 0.0178), PCNAmax (p = 0.0054) and PCNAcount (p < 0.001) predicted survival and in multivariate analysis PCNAcount (p = 0.006), patient age (p = 0.040) and tumour diameter (p = 0.042) were related independently to survival. The results indicate that PCNA immunolabeling has prognostic value in local breast cancer.
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PMID:Proliferating cell nuclear antigen (PCNA) immunolabeling as a prognostic factor in axillary lymph node negative breast cancer. 810 Jan 28

Expression of proliferating cell nuclear antigen (PCNA) has been shown to be of prognostic value in patients with certain types of cancer. The aim of this study was to determine if the abundance of PCNA is inversely correlated with survival of patients with breast cancer. Paraffin blocks were available from 68 patients, all of whom had been followed clinically for at least 5 years. Sections from 20 patients showed no reactivity to PCNA and were excluded from the study because it was not possible to distinguish between true negatives and false negatives (those due to poor fixation of the original specimens). The PCNA index (the number of stained cancer cells as a percentage of the total number of cancer cells present) was calculated for the remaining 48 patients. Results were analysed by Wilcoxon's rank sum test (two tailed) and Pearson's correlation coefficient. There was no statistical difference between the PCNA indices of those patients dead from their disease within 5 years of diagnosis compared with those alive and without signs of breast cancer at 5 years. There was also no correlation between PCNA index and size of the cancer, involvement of axillary lymph nodes, time to recurrence or time to death. There was, however, a significant correlation between PCNA index and histological grade (P = 0.029). It appears that PCNA staining of stored paraffin sections is of little prognostic value in patients with breast cancer.
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PMID:PCNA immunostaining in breast cancer. 810 8

Within the past few years, the measurement of serum and tissue markers, especially the latter, has assumed a more significant role influencing clinical decisions about treatment and follow-up of patients with malignant disease. Breast cancer is a useful paradigm to illustrate the types and importance of these various markers. Tissue markers, including nuclear grade, steroid hormone receptors, DNA index, ploidy, expression of oncogenes or tumor-suppressor genes, epidermal growth factors, cathepsin D, proliferating cell nuclear antigen (PCNA), Ki-67, p32, and others, may influence choices of initial treatment as well as adjuvant chemotherapy and (or) hormone administration. The serial measurement of serum markers, those currently available and those on the horizon, for example, may offer a way to monitor patients at risk for recurrent cancer. Although the current role of these markers may be controversial, as information about them is collected and refined, in the future perhaps a panel of such studies could be incorporated into forthcoming clinical staging systems for carcinoma of the breast and other malignancies to define both treatment and outcome.
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PMID:Clinical applications of serum and tissue markers in malignant disease: breast cancer as the paradigm. 822 51


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