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Query: UMLS:C0027627 (metastases)
 103,950 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This review examines ways in which histopathologists can attempt to predict whether a neoplasm will metastasize by microscopic examination of surgically removed samples of human neoplasms. These include qualitative description, semi-quantitative analysis of differentiation and proliferation, or of the nature of the edge of the neoplasm, and quantitative analysis of mitotic counts. More recently measurement of DNA content, analysis of DNA turnover, measurement of proliferation antigens, measurement of nucleolar organizing areas, counting nucleoli, morphometry of nuclei and identification of genetic change have become possible. There is no test capable of uniform accurate prediction of prognosis. In certain types of neoplasms in individual sites useful prognostic information can be obtained either by rigorous semi-quantitative microscopic analysis or by quantitative microscopical analysis. There is still doubt as to whether newer quantitative techniques will perform uniformly better than older semi-quantitative techniques. The simple subjective statement "high-grade malignancy, average malignancy, low malignancy" is better than elaborate non-reproducible pseudo-quantitation.
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PMID:Will a tumor metastasize? Quantitate, semi-quantitate or pseudo-quantitate? A brief review of the microscopic prediction of tumor metastasis. 152 Sep 9

We have previously reported a complete allelotype study of 86 primary breast carcinomas, in which each non-acrocentric chromosome arm was studied with at least one polymorphic DNA-marker for the presence of allelic imbalance (AI, allelic loss or allelic gain) in the tumor. Here we report the statistical analysis of this data set, investigating the relationships between AI, DNA aneuploidy and several clinico-pathological parameters of tumor progression. AI on 13 different chromosome arms, including 3p, 11p, and 17p, correlated significantly with the total number of AI events at other sites, suggesting that they are progression-related events. AI at 1q and 16q did not show such a correlation and may thus represent earlier events. Mean fractional allelic imbalance (FAI) was significantly higher in flow cytometrically aneuploid tumors than in diploid tumors (0.27 vs. 0.17, p = 0.007), and was highest in hypotetraploid tumors (0.37). This suggests that tetraploidization followed by chromosome segregation may underlie the development of AI at multiple sites. No correlation was found between mean FAI and clinico-pathological variables such as lymph-node involvement, stage, age, estrogen-receptor content and development of distant metastases, although there was a noticeable trend towards impaired survival for those patients with a higher-than-median FAI value.
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PMID:Fractional allelic imbalance in human breast cancer increases with tetraploidization and chromosome loss. 153 20

Regional metastases are a major determinant in the treatment outcome of patients with squamous cell carcinoma of the head and neck. Metastases do not respond as well to cytotoxic therapy as do primary tumors. DNA diploid tumors or tumor components also respond poorly to intermittent cytotoxic therapy. In our series of 497 patients with squamous cell carcinoma of the head and neck, the percentage of pure DNA diploid tumors and the mean DNA indexes in 497 primary tumors and 82 regional metastases were 34% and 1.54 and 50% and 1.34, respectively. Paired comparisons were performed in 61 patients and revealed a statistically significant increase in the frequency of DNA diploid tumors (27.4% to 41.2%) in associated lymph node metastases. The clinical observation that patients with squamous cell carcinoma of the head and neck and regional lymph node metastases have a poorer prognosis and a poorer response to cytotoxic therapy may in part be explained by the increased incidence of DNA diploid tumors in their regional lymph nodes, and the poorer response of such tumors to cytotoxic therapy.
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PMID:DNA ploidy of primary and metastatic squamous cell head and neck cancers. 154 Mar 51

The molecular genetic alterations in colorectal carcinoma are among the best understood of any common human cancer. Identified abnormalities include both dominant-acting oncogenes (ras, myc, src) and suppressor genes which undergo inactivation or deletion (deleted in colorectal carcinoma gene [DCC], p53, adenomatous polyposis coli gene [APC], and probably loci on chromosomes 1p and 22q). Accumulation of multiple abnormalities is evident in the adenoma-carcinoma sequence with a preferential order, and alteration of DNA methylation is an especially early event. Identification of molecular genetic markers useful for classification and staging of colorectal carcinoma is in its infancy. Deletion of the p53 gene on chromosome 17p, deletion of the DCC gene on 18q, and high fractional allelic loss (fraction of evaluable nonacrocentric autosomal arms with deletion) have been associated with distant metastases and with poorer prognosis in patients without initial evidence of disseminated disease. Additional studies are needed to determine the possible role of these alterations in clinical management.
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PMID:Molecular genetic alterations as potential prognostic indicators in colorectal carcinoma. 154 Sep

Immunohistochemical staining for the p53 protein was performed in 107 snap frozen primary endometrial adenocarcinomas and 15 benign uterine tissues using monoclonal antibody PAb1801. No staining was seen in benign samples, whereas intense nuclear staining of cancer cells consistent with overexpression of the p53 protein was observed in 22 of 107 cancers (21%). p53 overexpression was more frequent in advanced (Stage III/IV) cancers (41%) than in early (Stage I/II) cancers (9%) (P less than 0.001), and also was associated with nonendometrioid histology (P = 0.008), positive peritoneal cytology (P = 0.01), extrauterine metastases (P = 0.003), and negative progesterone receptor status (P = 0.04). To confirm the relationship between p53 overexpression and mutation, p53 mRNA from 8 cancers was reverse transcribed and amplified using the polymerase chain reaction. DNA sequencing revealed point mutations in each of the 5 cancers that overexpressed p53, whereas the wild-type sequence was found in 3 cancers that did not overexpress the protein. Each of the 5 mutations resulted in an amino acid substitution in a highly conserved region of the p53 gene where mutations have been found in other cancers. Further studies are warranted to determine whether the association between p53 overexpression and advanced stage disease is due to accumulation of genetic lesions during tumor progression or whether p53 alterations confer a more virulent phenotype.
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PMID:Overexpression and mutation of p53 in endometrial carcinoma. 154 Sep 70

Serum sialyl-Tn antigen level was studied in 117 cases of colorectal cancer. The positive rates for serum sialyl-Tn antigen were 23.1% in primary colorectal cancer. There is a significant correlation between the positive rates of serum sialyl-Tn antigen and liver metastases, peritoneal dissemination, or lymph node metastases. The survival rate for patients with sialyl-Tn antigen positive sera was lower than those with sialyl-Tn antigen negative. Among patients who underwent curative operation, patients with sialyl-Tn positive sera gave a recurrence rate of 35.7%, while those with sialyl-Tn negative sera recorded a recurrence rate of 14.7%. There is no correlation between the positive rates of serum sialyl-Tn antigen and DNA ploidy pattern. Serum sialyl-Tn antigen levels may be a useful indicator in projecting the prognosis of colorectal cancer.
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PMID:[Serum sialyl-Tn antigen in colorectal cancer and its relationship to prognosis]. 154 61

The antimetastatic potential of a novel chemotherapeutic agent, alpha-difluoromethylornithine (DFMO), was evaluated in a murine model of intraocular melanoma. In vivo studies demonstrated that DFMO retarded the growth and spontaneous metastasis of murine intraocular melanomas. Further studies indicated that oral DFMO also exercised antimetastatic effects against the blood-borne stage of melanoma metastases. In vitro studies revealed that DFMO exerted impressive antiproliferative effects on three murine melanoma cell lines, four human cutaneous melanoma cell lines, one human uveal melanoma cell line, and one conjunctival melanoma cell line. DFMO inhibited in vitro DNA synthesis in human cutaneous melanoma cell lines by 84%-98% and that in two human ocular melanoma cell cultures by 62% and 86%, respectively. DFMO possesses several characteristics that render it an attractive chemotherapeutic agent for potential use in the management of uveal melanoma. These include its antiproliferative effect against a wide range of murine and human melanomas, its extremely low toxicity, and its ease of administration.
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PMID:Prevention of metastasis of intraocular melanoma in mice treated with difluoromethylornithine. 154 72

The use of non-radioactive in situ hybridization (ISH) with chromosome-specific repetitive DNA probes to study genomic changes, aneuploidy, and heterogeneity during melanocytic tumor progression, relies on its applicability to non-mitotic interphase nuclei, present in cell suspensions and tissue sections. Therefore, we studied the feasibility of detecting numerical aberrations with respect to the (peri-) centromere regions of chromosomes 1 and 7 in intact nuclei of two human melanoma cell lines with different metastatic behavior in nude mice. In addition, we used paraffin sections from xenograft lesions, obtained by inoculation of these cell lines in nude mice (subcutaneous tumors and spontaneous lung metastases). Paraffin sections from the original primary cutaneous melanoma (with a subepidermal and a dermal part) and two loco-regional metastases were also studied, one of which was the source for the cell lines. These cells and tissues represent examples of materials used in different approaches to the study of melanocytic tumor progression. Regarding the targeted sequences, ISH analysis showed that both cell lines were heterogeneous and aneuploid. The results correlated well with those obtained by ISH on metaphase spreads. Differences between the lines, which could not be detected by flow-cytometric or conventional karyotyping analysis, included data suggestive of a polyploid subpopulation and an extra copy of chromosome 7 in the metastasizing cell line. The polyploid population could be detected also in the paraffin sections of the corresponding subcutaneous xenografts and lung metastases in the mice. Both areas in the patients' primary melanoma could be evaluated separately and showed similar supernumerary aberrations of the chromosome-specific targets. These abnormalities matched those found in both metastases. Our results demonstrate that ISH can be used to visualize genomic abnormalities at the single-cell level in melanocytic nuclei in their natural context, which makes it a promising tool in the histopathology of melanocytic lesions and in the study of melanocytic tumor progression.
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PMID:In situ detection of supernumerary aberrations of chromosome-specific repetitive DNA targets in interphase nuclei in human melanoma cell lines and tissue sections. 154 28

DNA fingerprinting with the minisatellite probes 33.6 and 33.15 was used to screen for genetic abnormalities in primary tumors of a variety of organs and, where appropriate, their metastases, obtained from 32 patients. The constitutional DNA of each host, obtained from blood leukocytes or normal tissue, was used to produce control, individual-specific fingerprints for comparison with those of their tumor. Fingerprints obtained with probe 33.6 showed differences between tumor and host fingerprints in 69% of patients and those produced with 33.15 in 55%. The most common change was loss or reduction in the intensity of one or more bands, but the appearance of new bands, not present in the fingerprint of the constitutional DNA, was also noted in several tumor DNA samples. The findings are interpreted as indicating loss or rearrangement of expressed sequences in the chromosomal regions adjacent to the hypervariable tandem repeat intron arrays which are detected by these probes. In three patients further differences were identified between primary tumors and their metastatic deposits. With this technique it is possible to perform simultaneous multilocus screening of the genome and the present results show that it has potential for identification of as yet unknown abnormalities in DNA constitution, which may be of pathogenetic significance.
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PMID:DNA fingerprinting survey of various human tumors and their metastases. 155 21

In 164 breast carcinomas the presence of peritumoral lymphatic vessel invasion (PLVI) was evaluated and correlated with other known indicators of prognosis and with the clinical outcome of the patients. Overall 22% of tumors were PLVI-positive. The presence of PLVI was significantly associated with axillary node involvement (p less than 0.0001) and tumor size (p = 0.005), and tended toward an association with grading (p = 0.065). No significant association was found between PLVI and steroid hormone receptors, DNA ploidy, or proliferative activity. Univariate analysis shows that peritumoral vessel invasion was significantly associated with a higher risk of recurrence (p = 0.012) and with a trend toward shorter survival (p = 0.074). Besides the presence of PLVI, prognosis was significantly worse also for patients with high proliferative aneuploid tumors and with axillary node metastases. Moreover, within the subsets of patients generally considered to have good prognosis, the presence of PLVI identified patients with a trend for higher risk such as those with PLVI-positive diploid tumors, PLVI-positive low-proliferative tumors, and PLVI-positive node-negative tumors. Adopting multivariate analysis, PLVI failed to retain prognostic importance when adjusted for node status, DNA ploidy, and proliferative activity. In conclusion, we found that the presence of PLVI has prognostic significance when singly evaluated. Multivariate analysis shows that PLVI is not an independent prognostic factor in stage I-II breast cancer.
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PMID:Peritumoral lymphatic vessel invasion compared with DNA ploidy, proliferative activity, and other pathologic features as prognostic indicators in operable breast cancer. 157 72


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