Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027627 (metastases)
 103,950 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The prognosis for patients with renal cell carcinoma is difficult to predict. For other malignant tumors, predictions of prognosis have been facilitated by analysis of tumor DNA content. It seemed therefore important to investigate DNA content and its possible prognostic value in renal cell carcinoma. DNA measurements were performed retrospectively on paraffin sections or aspiration biopsy smears by static cytometry. Paraffin-embedded tissues were also analysed, after enzymatic isolation of nuclei, using flow cytometry. Prospective analyses were performed by flow cytometry of fresh tissues. Four different methods for analysis of DNA content were compared in 30 samples: flow cytometry of fresh and paraffin-embedded tissues and static cytometry on imprints and paraffin sections. Comparable results were obtained for all 4 methods (r = 0.744-0.970, p less than 0.001). Histopathologic grade correlated with tumor DNA content. All grade 1 and 81% of grade 2 tumors were diploid. Grade 3 tumors were most common and about 50% of these were aneuploid. 83% of grade 4 tumors had an aneuploid DNA content. By analysis of 8 different samples from each of 25 tumors, a considerable heterogeneity was found in 11 of 13 non-diploid whereas 12 tumors were homogenously diploid. 55 patients without distant metastases at nephrectomy were grouped with respect to survival time. Patients surviving more than 10 years had nearly all diploid tumors (32/33) whereas all 22 patients surviving less than 4 years had aneuploid tumors. For 32 patients with distant metastases, analyzed retrospectively, the survival time was significantly correlated to the DNA content of the metastases. For their primary tumors no such correlation was found, when only one sample was analysed. In contrast, by prospective analysis of multiple samples from the primary tumors of 23 other patients with distant metastases, the DNA content gave important prognostic information. Thus, analysis of multiple samples improved the prognostic information given by the DNA content in primary tumors. The metastases were more frequently aneuploid, as compared to the primary tumors, indicating higher metastatic ability of aneuploid cell populations. Occasionally, in patients with aneuploid cell clones in the primary tumors, metastases with a diploid DNA content were found. The DNA content of the metastases provided additional prognostic information to that obtained from the primary tumors.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:DNA content in renal cell carcinoma. A clinical study with special reference to tumor heterogeneity and prognosis. 347 40

Flow cytometric DNA analysis of isolated nuclei was performed on 14 lesions occurring in ten children with adrenocortical tumors. Unimodal DNA content distributions were obtained from seven tumors occurring in patients without metastases 2 to 18 years after diagnosis. Abnormal DNA contents were detected in all four primary lesions, which subsequently metastasized, and in the tumor of one patient who was followed for less than 2 years. Paraffin and frozen preparations were virtually identical, as were the analyses of the primary, recurrent, and metastatic disease occurring in one patient. These observations suggest that DNA content abnormalities detected by flow cytometry correlate with metastases, and may provide an objective measure of the biologic potential of these tumors.
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PMID:Flow cytometric DNA analysis of adrenocortical tumors in children. 356 66

Paraffin-embedded surgical specimens from 120 patients who underwent resections for primary untreated colonic adenocarcinoma were examined for proliferative activity, DNA aneuploidy, DNA index, and the proportion of aneuploid cells by flow cytometry. The results were correlated with survival times and clinical characteristics of the patients. The presence of metastases, both distant and restricted to local lymph nodes, was found to be a more potent adverse prognostic indicator than any DNA flow cytometry-derived parameter. Additional analyses were performed following stratification of patients into two groups on the basis of presence or absence of metastases. Analysis of 60 patients without metastatic involvement revealed a significant correlation between high proliferative activity, defined as more than 20% of cells in S-phase, and DNA aneuploidy. In fact, high proliferative activity was shown to be a more powerful adverse prognostic indicator in relation to survival than DNA aneuploidy in these cases after multivariate analysis. These results suggest that differences in proliferative activity may be an important biologic factor operative in the variable prognosis seen in colonic adenocarcinoma. In addition, they re-emphasize the importance of stratifying patients into groups based on metastatic involvement when evaluating other possible prognostic features in this disease.
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PMID:Prognostic implications of proliferative activity and DNA aneuploidy in colonic adenocarcinomas. 362 22

Multiple, synchronous, apparently primary carcinomas of the colon are a relatively common occurrence. The DNA ploidy in 23 colon carcinomas from 10 patients was determined to see if this parameter supported common or independent origins for such synchronous lesions. Paraffin blocks of each tumor were prepared for flow cytometry, then analyzed for nuclear DNA content. In 3 of the 10 cases, the tumors within each colon differed with respect to DNA ploidy; in four cases all tumors were diploid; and in three cases both (all) tumors within each colon had identical aneuploid DNA indices. Tumors from the same colon with identical DNA histograms often had dissimilar histology. The replicate aneuploid DNA indices strongly suggest a common origin for the multiple tumors within these colons; tumors in the other groups are compatible with either single or multiple origins. These findings suggest that multiple "primary" colon carcinomas may, in some cases, arise as translumenal metastases from an initial single lesion.
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PMID:Origin of multiple "primary" colon carcinomas. A retrospective flow cytometric study. 375 24

The histological detection of tumour metastases in axillary lymph nodes from cases of breast carcinoma is of major prognostic significance, but may be difficult when metastases are of microscopic size. We have therefore investigated whether immunohistological techniques can increase the accuracy of metastasis detection in axillary lymph nodes. Forty-five cases of breast carcinoma were studied, in all of whom the axillary lymph nodes had been reported as free of metastases. Paraffin sections from these cases were stained by immunoenzymatic techniques, using monoclonal antibodies directed against human milk fat globule membrane antigen ("anti-EMA") and against epithelial intermediate filaments ("anti-keratin"). In 4/12 cases of lobular carcinoma and in 3/33 cases of ductal carcinoma, previously unsuspected micrometastases were revealed by immunohistological staining, representing an overall increase in detection rate of 15% (and of 33% for the lobular carcinoma cases). In addition to this group of 45 histologically "negative" biopsies, 12 samples were studied in which only a proportion of the nodes had been reported as containing tumour. In 5 of these cases immunostaining revealed previously undetected metastases. These findings suggest that immunohistological analysis may have a routine role to play in the staging of breast carcinoma. It is noted that the 15% increase in diagnostic accuracy achieved in the present study is comparable to the proportion of breast carcinoma patients in whom disseminated disease develops despite their axillary lymph nodes being reported as tumour-free at the time of surgery.
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PMID:The immunocytochemical detection of axillary micrometastases in breast cancer. 638 May 53

MO4 mouse fibrosarcoma cells, B16 mouse melanoma cells, HeLa human cervical carcinoma cells, and LICR (LOND)-HN-4 human laryngeal carcinoma cells were shown to invade into precultured fragments of 9-day-old chick cardiac muscle in three-dimensional culture. Paraffin sections from such cultures were stained with an antiserum against chick heart following the unlabeled antibody enzyme method. The immunostaining demonstrated (1) differences in the rate and the way by which the four types of malignant cells occupied and replaced the chick cardiac muscle, and (2) the phagocytic activity of the four types of invading cells in three-dimensional culture.
Invasion Metastasis 1981
PMID:Immunohistochemical study of embryonic chick heart invaded by malignant cells in three-dimensional culture. 718 86

The relevance of silver-stained NORs for classifications and prognosis was investigated in breast tissue. Paraffin sections from 137 cases of invasive ductal breast carcinomas and 12 cases with non-tumorous ductus epithelium as controls were stained according to a modified technique and analysed. From the cancer cases follow-up data up to 10 years (45 to 165 months) and in addition clinical, histological and several DNA distribution parameters were available. The nuclei and the silver grains were measured by means of a semiautomatic image analysis system. Significant differences in AgNOR features were found between controls and diploid tumors (p < or = 0.001), diploid and aneuploid tumors (p < or = 0.001), Bloom-Richardson-gradings I, II, and III (p < or = 0.001), and between the tumor cells from patients developing metastases within 5 years and those without (p < or = 0.002). The prognostic significance of AgNORs was estimated using Cox regression analysis. Four AgNOR features were correlated significantly with survival time. In a multivariate approach offering all parameters available an AgNOR parameter (CV of relative area AgNORs) ranked at the third position beyond the SD of DNA distribution and pTNM-staging. Considering the metastases-free interval of patients the same AgNOR feature showed an independent prognostic validity.
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PMID:Nucleolus organizer regions (AgNORs) in ductal mammary carcinoma. Comparison with classifications and prognosis. 752 Jan 63

Nearly all primary prostatic carcinomas have been found to express the androgen receptor (AR) protein, which is the intracellular mediator of androgen action. To gain a better insight into the mechanisms of androgen independence of advanced prostatic carcinoma, it is important to know whether the AR is also present in metastases of androgen-independent tumors. We have assessed the status of the AR and the prostate-specific antigen in 22 metastases of 18 patients with progressive prostate cancer. In 18 cases, the metastases were localized in bone, in 3 cases in the epidural space, and in 1 case in the periosteum. All but one patient had received some kind of endocrine treatment for prostatic carcinoma. Paraffin-embedded tissue sections were stained for the AR following a streptavidinbiotin-peroxidase protocol with the polyclonal antibody PG-21, which is directed against amino acids 1 through 21 of the rat and the human AR. The percentage of AR-positive cells was evaluated on the basis of an arbitrary 4-point scale. All 22 tumor metastases displayed AR positivity. One AR-positive metastatic lesion did not stain for prostate-specific antigen, but in all other metastases, this protein was detected by means of immunohistochemistry. The present study provides evidence that, unlike androgen-independent prostatic carcinoma cell lines, distant prostatic carcinoma metastases do express the AR. These findings indicate that the AR may be involved in the progression of prostate cancer.
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PMID:Distant metastases from prostatic carcinoma express androgen receptor protein. 754 9

Paraffin-embedded tissue from the primary tumours of 116 patients with malignant melanoma, and in 40 cases also from corresponding metastases, were examined for accumulation of p53 protein. The fraction of tumours with positive p53 immunostaining was 13% in the least invasive and 36% in the most invasive primary lesions and 48% in the metastases. Where comparisons could be made, both the level and pattern of p53 immunoreactivity were the same in the primary and metastatic tumours. Nine (50%) patients with p53-positive and 34 (39%) with p53-negative primaries relapsed during the first 5 years, but no difference in disease-free period was observed between the two groups. However, an overall longer survival time was observed among patients with p53-positive primaries, especially for those with tumours less invasive than 3.0 mm. Notably, all 11 patients in this group were alive 5 years after diagnosis of the disease, whereas 15 out of 70 (21%) patients with p53-negative tumours died in same period. The results show that an increased level of p53 protein does not indicate increased degree of malignancy in melanoma, but rather suggests a more favourable disease progression.
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PMID:Accumulation of p53 protein in human malignant melanoma. Relationship to clinical outcome. 764 May 20

Paraffin-embedded, formalin-fixed tissue (PEFFT) specimens from a subset of breast cancer patients were analyzed by immunohistochemistry to determine whether or not the presence of P-glycoprotein identified chemotherapy resistance. Two antibodies, C219 (monoclonal) and Ab1 (polyclonal), demonstrated appropriate immunostaining. Retrospectively and prospectively, P-glycoprotein expression was determined from PEFFT of 20 breast cancer biopsies (19 patients with locally advanced or metastatic disease). Immunohistochemical staining was graded for number of positive cells (N0 to N4) and intensity (I0 to I3). The immunostaining N and I of both antibodies were similar. There was no correlation between N, (P = 0.13) or I, (P = 0.67) and chemotherapy response or between N, (P = 0.63) or I, (P = 0.89) and survival. Five patients had residual cancer at repeat biopsy after systemic chemotherapy for locally advanced disease. These specimens had similar N and I as the primary cancer. This assay accurately identifies P-glycoprotein expression in PEFFT and revealed no correlation between expression and chemotherapy response or survival.
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PMID:Immunohistochemical analysis of P-glycoprotein expression in breast cancer: clinical correlations. 776 69


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