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Query: UMLS:C0006142 (breast cancer)
 160,383 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We evaluated whether proliferating cell nuclear antigen (PCNA) immunohistochemistry with antigen retrieval could be used as a measure of cell proliferation in archival, formalin-fixed, paraffin-embedded tissues and whether the staining results have long-term prognostic significance in axillary node-negative breast cancer. Primary tumor samples obtained from 109 axillary-node-negative breast cancer cases were used for the study. The best staining results were obtained with the 19A2 antibody after microwave heating in a solution of saturated lead thiocyanate. Using this method, there was a significant correlation (linear regression, r = 0.580, P < 0.001) between the proportion of PCNA19A2-positive carcinoma cells (PCNA19A2 score) and DNA flow cytometric S phase fraction. A high PCNA19A2 score was associated with high mitotic count, DNA aneuploidy, and absence of estrogen receptors. Axillary-node-negative patients with a high PCNA19A2 score (cut-point 8%) had significantly worse prognosis than those with a low PCNA19A2 score (P = 0.008). According to a Cox multivariate analysis, PCNA19A2 score had independent prognostic value but only if S phase fraction was excluded from the analysis. In our study, the PCNAPC10 score correlated weakly only with primary tumor size (analysis of variance) and prognosis (5-year univariate survival analysis), but the significance of these findings needs further evaluation. In conclusion, PCNA immunohistochemistry with the 19A2 antibody after an appropriate antigen retrieval treatment may offer a useful alternative to DNA flow cytometry for the analysis of cell proliferation activity from formalin-fixed, paraffin-embedded breast carcinomas.
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PMID:Proliferating cell nuclear antigen immunohistochemistry using monoclonal antibody 19A2 and a new antigen retrieval technique has prognostic impact in archival paraffin-embedded node-negative breast cancer. 768 59

Sixty-six unselected breast cancers were analyzed in cytologic smears and histologic sections for the expression of Ki-67, proliferating cell nuclear antigen (PCNA), estrogen receptor protein (ERP), and p53 protein using a standard immunochemical method. The results, expressed as both positive cases and labelling index (LI), were compared with clinical and pathobiological variables. Ki-67 and PCNA immunostaining was seen in all cases, whereas ERP was detectable in 46/63 cases and p53 protein in 20/66 cases. The expression of these markers was generally lower in cytology than in histology, though the differences were not statistically significant. PCNA-LI and Ki-67-LI were closely correlated (P < 0.001), the mean PCNA:Ki-67 ratio being 0.92 +/- 0.57. Occasional discrepancies, however, were found. PCNA and Ki-67 expression was associated with an increase in histologic grade and a decrease in ERP content of tumors, whereas p53 was statistically associated with no clinical or pathobiological variables. The data suggest that proliferative activity and oncogene overexpression may be reliably evaluated in breast cancer by FNA cytology, though PCNA is not a suitable indicator for cell proliferation. The results do not resolve the issue as to whether immunostaining for p53 protein constitutes a dedifferentiation product of the tumor, or is a fundamental aspect of the malignant progression. Survival studies in a larger series of tumors are thus needed to elucidate this point.
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PMID:Expression of proliferating cell nuclear antigen, Ki-67 antigen, estrogen receptor protein, and tumor suppressor p53 gene in cytologic samples of breast cancer: an immunochemical study with clinical, pathobiological, and histologic correlations. 781 60

An increasing body of evidence suggests that in addition to conventional histopathologic tumor characteristics, DNA content measurements, cell kinetic data, and investigations of tumor suppressor gene expressions might be of valuable information in breast cancer patients. Against this background we investigated immunohistochemically overexpression of the interphase associated protein proliferating cell nuclear antigen (PCNA) and the mutant p53 protein in routinely paraffin-embedded surgical specimens from 180 breast cancer patients with known nuclear DNA profiles. The mean clinical follow-up was 16 years (range 13-20 years). The percentage of PCNA immunoreactive tumor cell nuclei ranged between < 5% and 60% (mean 13.59 +/- 10.85%). There was a direct association between high levels of PCNA expression (> 20%) and p53 protein overexpression (p = 0.001), high histologic tumor grade (p = 0.009), and DNA aneuploidy (p = 0.019). Mutant p53 protein overexpression was found in 44 of 180 (24%) cases and was significantly related to high histologic tumor grade (p = 0.004), DNA aneuploidy (p = 0.001), and high levels of PCNA expression (p = 0.001). Patients with highly proliferative carcinomas (> 20% PCNA expression) had a shortened distant metastases-free survival when their neoplasms overexpressed p53. In contrast, the distant metastases-free survival of patients with highly proliferative, p53-negative tumors was significantly longer (p = 0.03). Immunohistochemical p53 protein overexpression thus appears to be indicative of an increased malignant potential in breast cancer patients. Highly proliferative tumors composed of p53 immunoreactive neoplastic cells clinically seem to behave more aggressively than the highly proliferative p53-negative tumors.
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PMID:Association of immunohistochemical p53 tumor suppressor gene protein overexpression with prognosis in highly proliferative human mammary adenocarcinomas. 784 4

Breast cancers often contain different clones of tumor cells. Attention to the cellular properties of breast cancer metastases may identify characteristics in primary tumors that are associated with metastasis. Such characteristics could include DNA content, cell proliferation, abnormal oncogene expression, or relative cell population (clonal dominance). We examined DNA ploidy (image analysis), proliferation index (proliferating cell nuclear antigen-1 immunostaining), and expression of Her-2/neu oncoprotein in 17 invasive breast cancer samples (36 primary tumor samples) and 82 corresponding regional metastases. In all samples the primary tumor was multiclonal (usually biclonal) by DNA ploidy analysis. In approximately 90% of metastatic DNA clones (30 of 34) the corresponding clone was identified in a primary tumor sample representing 25% or more of the tumor cell population (significant clone). A majority DNA clone (> or = of tumor cell population) existed in 60% (21 of 36) of primary tumor samples and in 70% (60 of 82) of metastases (30% diploid v 70% nondiploid in both groups). In approximately 50% of metastases (37 of 82) an unexpected majority clone was identified (not a majority in any primary tumor sample) and the ratio of diploid to nondiploid clones also was 30% to 70%. However, in 80% of majority metastatic clones (46 of 60) that clone was a significant primary tumor clone. Proliferation index was quite variable in primary tumor samples and in corresponding metastases. Overexpression of Her-2/neu oncoprotein in the primary tumor of seven of 10 patients also was identified in all corresponding metastases in five of seven patients and in some metastases in two of seven patients. The metastases in three Her-2/neu-negative patients were all negative. We conclude that (1) DNA clones are stable after metastasis, (2) clonal majorities in metastases reflect clones identified in primary tumors, (3) different metastatic clones from an individual tumor can establish clonal majorities, (4) neither diploid nor aneuploid cells have a metastatic advantage in breast cancer, (5) proliferation indices are heterogeneous, and (6) overexpression of Her-2/neu is usually consistent between primary tumors and corresponding metastases.
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PMID:Breast cancer heterogeneity: evaluation of clonality in primary and metastatic lesions. 786 51

For a variety of human malignancies such as breast cancer and cancer of the prostate, p53 oncoprotein overexpression indicating an alteration of the p53 tumor-suppressor gene has been described as a prognostic factor for a poor clinical outcome. To investigate the overexpression of p53 oncoprotein in transitional-cell carcinoma of the bladder, 58 bladder cancer specimens of different clinical stages and histological grades were investigated using an immunohistochemical approach. A correlation between p53 positivity and tumor stage was observed, with an increase from 38.5% of superficial (Ta) tumors to 83.3% of muscle-invasive (T3/T4) tumors staining positively for p53 oncoprotein. Furthermore, an increase from 46.7% of G1 tumors to 75% of G3 tumors was observed. In 22 of 25 (87%) informative patients the results of the immunohistochemical staining could be verified by the determination of p53 mutations as detected by polymerase chain reaction (PCR)-directed analysis of restriction-fragment-length polymorphisms (RFLP). To determine the prognostic value of p53 immunohistochemistry for the clinical course of superficial bladder cancer, the overexpression of p53 oncoprotein was investigated in 41 patients with superficial bladder tumors (T1) undergoing complete transurethral tumor resection. The detection of p53 protein was correlated with further clinically important variables such as sex, age, histological grading, former instillation therapy, and immunohistochemical determination of the proliferation rate by staining for PCNA (proliferating-cell nuclear antigen; monoclonal antibody PC10).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Detection of P53 tumor-suppressor-gene protein in bladder tumors and prostate cancer: possible clinical implications. 788 74

Expression of proliferating cell nuclear antigen (PCNA) and c-erbB-2 oncoprotein has been assessed in 471 women with breast cancer to evaluate their prognostic value as compared to conventional histopathological factors. In univariate analysis, high PCNA expression (> or = 20%) predicted a significantly worse survival in lymph-node-negative tumors (univariate P = 0.031). However, the effect disappeared in multivariate analysis and the histological grade remained the only independent factor for this group. Despite its close correlation to histological grade (P < 0.001), PCNA expression discriminated subsets with different survival within the heterogeneous group of moderately differentiated tumors (univariate P = 0.073, multivariate P = 0.075). PCNA expression was not found to be a significant prognostic factor in lymph-node-positive tumors, thus it was of limited value for breast cancer patients as a whole. c-erbB-2 protein overexpression was associated with a worse survival (univariate P = 0.019, multivariate P = 0.057) for the entire group of patients. The effect was mainly attributed to the significance of c-erbB-2 as an independent factor in lymph-node-positive (up to three nodes, multivariate P = 0.04; four or more nodes: multivariate P = 0.017) and large tumors (> 2 cm: multivariate P = 0.002). c-erbB-2 was without significance in lymph-node-negative patients. Though both factors might amplify the prognostic information for distinct patient subsets they do not achieve the strong prognostic value of conventional histopathological features in breast cancer.
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PMID:Prognostic value of proliferating cell nuclear antigen and c-erbB-2 compared with conventional histopathological factors in breast cancer. 788 73

In an immunohistochemical study of 490 primary breast cancer patients with a follow-up period of more than 10 years, we found that p53 was not a prognostic factor for disease-free or overall survival among the whole cohort or among lymph node-positive or -negative patients. In a multiple logistic regression model classical histopathological parameters, such as lymph node status, number of mitoses, histological grade, and absence of progesterone receptors, were independent, poor prognostic predictors. In univeriate analysis p53 immunoreactivity was positively correlated with the absence of tubule formation, high histological grade (poor differentiation), absence of estrogen receptors (ER), and a high proliferating cell nuclear antigen (PCNA) score (ie, parameters indicative of an aggressive phenotype). The lack of prognostic significance may be attributable partly to the method used, because immunohistochemistry underdetects rather than overdetects p53 protein. No correlation between p53 and c-erbB-2-oncoprotein was demonstrated.
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PMID:An immunohistochemical study of p53 with correlations to histopathological parameters, c-erbB-2, proliferating cell nuclear antigen, and prognosis. 789 Feb 81

The expression of the S-phase associated, nuclear protein proliferating cell nuclear antigen (PCNA) was investigated in routinely paraffin-embedded surgical specimens from 209 breast cancer patients. Cytometric DNA assessments were performed on fine-needle aspirates, upon which the primary diagnosis of breast cancer had been based. The mean clinical follow-up was 16 years (range 13-20 years). The percentage of PCNA immunoreactive tumour cells ranged between less than 5 to 60% (mean value 13.34%). There was a direct association between PCNA expression, high histological tumour grade (p < 0.01), and DNA aneuploidy (p = 0.009). In a subgroup of 22 patients with near-diploid DNA distribution patterns the PCNA expression yielded additional prognostic information. Patients with tumours of near-diploid DNA histograms and more than 20% of PCNA immunoreactive neoplastic cells had a significantly worse clinical course, than patients with near-diploid tumours containing less than 20% PCNA immunoreactive cells (p = 0.0001). In contrast, the PCNA immunoreactivity did not yield additional prognostic information for patients with distinctly diploid or highly aneuploid tumour variants. In a multivariate analysis comprising all 209 patients, nodal status (p < 0.01), tumour size (p < 0.01), and DNA ploidy (p < 0.01) were found to have significant prognostic effect. The findings indicate that carcinomas characterised by high proliferative activity and near-diploid DNA distribution patterns can show rapid tumour progression. The combined assessment of the PCNA immunoreactivity and of the nuclear DNA content in routinely processed surgical specimens of breast cancer patients appears to be of prognostic value.
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PMID:Prognostic value of the combined assessment of proliferating cell nuclear antigen immunostaining and nuclear DNA content in invasive human mammary carcinomas. 790 39

This study was undertaken to relate the expression of the proliferating cell nuclear antigen (PCNA), a proliferation marker of putative prognostic significance, to some more established prognostic factors in a series of 60 consecutive breast cancer surgical specimens. PCNA was detected by the PC10 monoclonal antibody (MAb) using an immunohistochemical method and PCNA immunostaining was estimated on a semiquantitative basis, a cut-off value of 50% of positively stained tumour cells discriminating between the high (> 50%) and low (< 50%) PCNA grade. The PCNA grade did not correlate with tumour size and axillary node status. However, a high PCNA grade tended to be associated with a poor histological grade and there was an inverse relationship with oestrogen-receptor status, as determined by means of the immuno-histochemical staining for the oestrogen-induced pS2 protein. These conflicting results suggest that the possible prognostic usefulness of PCNA immunostaining, as a measure of cell proliferation rate, in breast cancer is yet to be demonstrated and can be validated only by direct relation to survival data.
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PMID:Cell proliferation in breast carcinoma assessed by a PCNA grading system and its relation to other prognostic variables. 790 63

The staining patterns obtained with two antibodies against proliferating cell nuclear antigen (PC10 and 19A2) and another cell cycle associated antibody (KiS1) were compared with each other and with a number of established prognostic markers of breast carcinoma. Although PC10 and 19A2 staining patterns were similar, only the latter was significantly associated with KiS1 antibody staining. These findings suggest that the two PCNA antibodies detect different epitopes. KiS1 was the only antibody to show an association with S phase fraction measured by flow cytometry (p < 0.001). It was also associated with histological grade (p = 0.003), oestrogen receptors (p = 0.045), and DNA index (p = 0.007). PC10 showed no association with any of the markers of prognosis, while 19A2 was associated with histological grade (p = 0.017) and oestrogen receptors (p = 0.043). The two PCNA antibodies do not seem to be of value in measuring proliferative activity nor do they seem to be associated with established markers of prognosis in breast cancer.
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PMID:Comparison of three cell cycle associated antigens as markers of proliferative activity and prognosis in breast carcinoma. 790 74


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