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Results for “Metastatic patterns”

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PubMed1993

Application of the p53 gene mutation pattern for differential diagnosis of primary versus metastatic lung carcinomas.

The p53 gene mutation pattern was used as a diagnostic marker of multiple and second primary lung carcinomas. Nine cases of multiple carcinoma, which were suspected clinicopathologically to be double or triple primary carcinomas, were examined for p53 protein expression by immunohistochemistry and for genetic abnormality of the p53 gene by polymerase chain reaction (PCR)-single-strand conformation polymorphism (SSCP) analysis. Nine tumors from four cases gave a positive result upon both immunostaining for the p53 protein and PCR-SSCP analysis of the p53 gene. These nine tumors showed different mobility shifts between exons 5 and 8. The four cases were diagnosed genetically as multiple primary carcinomas. To confirm the results of PCR-SSCP analysis, five tumors from two cases that showed different mobility shifts were further analyzed for their nucleotide sequences, and it was found that all of them had point mutations at different codons in exons 5 and 8. These findings suggest that the p53 gene mutation pattern is an effective marker for diagnosis of tumor multiplicity.

Base Sequence↗

PubMed1996

Brain metastases from colorectal cancer.

PURPOSE: We wished to determine the time interval before diagnosis of brain metastases from a colorectal origin, typical neurologic presentation, overall survival, and impact of type of treatment and metastatic growth patterns (solitary, location, etc.) on prognosis. METHODS: Between 1980 and 1994 we retrospectively identified 19 patients with metastatic colorectal cancer to the brain. Data were collected with regard to patient characteristics, location and stage of primary tumor, and extent and location of metastatic disease. Statistical analyses were performed with STATISTICA for Windows. RESULTS: Mean patient age was 66 (43-87) years. Primary tumor location was distributed throughout the colon; 58 percent had disseminated disease when first diagnosed. All patients were symptomatic. Lesions were solitary in 63 percent, unilateral in 89 percent, and cerebral in 53 percent. Overall median survival was 2.8 months; 1-year survival was 0 percent. Survival was longer following craniotomy (4.1 months) compared with radiation (2.8 months); however, survival was not affected by number or location of metastatic lesions or whether the brain was the sole site of metastatic disease. CONCLUSIONS: Brain metastases from colorectal cancer are infrequently the sole site of metastatic disease, and because survival is dismal regardless of form of therapy chosen, craniotomy is rarely indicated. Exception is the rare patient who has minimum neurologic impairment, a long disease-free interval, a solitary metastasis, and no extracranial disease.

Adult↗

PubMed1989

Lactate dehydrogenase isoenzyme patterns in serum of patients with metastatic liver disease.

Total lactate dehydrogenase (LD, EC 1.1.1.27) and LD isoenzymes were determined in serum of 170 patients with metastatic liver disease, 35 of whom had multiple metastatic sites. Overall, values of LD were above normal for 78% of the 170 patients. Half of the patients had an isomorphic pattern of LD isoenzymes (i.e., relative increase in all five isoenzymes); the other half had an increased LD-4,5 pattern, mostly a solitary increase in LD-5 only. Of those patients with normal LD values, 92% had the increased LD-4,5 pattern, whereas 70% of patients with LD values greater than 350 U/L had an isomorphic pattern of LD isoenzymes. All 35 patients with multiple metastatic sites had LD activity greater than 350 U/L; in the majority of them (74%) it was greater than 500 U/L; in 31 (89%), the increase was isomorphic. The diagnostic efficiency of the combined LD greater than 225 U/L (upper limit of normal) and increased LD-4,5 test results was much better than that of LD greater than 225 U/L alone (93% vs 74%). We conclude that serum LD and LD isoenzymes should be determined in every patient with suspected liver metastatic disease. The isomorphic pattern of LD isoenzymes is apparently associated with higher values for total LD and was common among the patients with multiple metastatic sites.

Aged↗

PubMedDate not supplied

Pseudodiverticulosis: unusual appearance for metastases to the ureter.

A rare pseudodiverticular pattern of metastatic malignancy to the ureter is reported along with pathologic findings at postmortem examination in three patients. There was no clinical or pathological obstruction. This pattern is due to malignancy-induced edema in the subepithelial connective tissues and muscularis propria causing displacement of these layers into the ureteral lumen resulting in an undulating epithelial surface. The epithelium itself is normal. Metastases to the ureter is uncommon in life unless associated with ureteral obstruction. Ureteral pseudodiverticulosis found in vivo in a nonobstructed patient with known metastatic malignancy is likely due to inflammatory causes and usually reversible with antibiotic and medical therapy. A patient with widespread malignancy showing nonreversibility of the ureteral pseudodiverticular pattern, even in the absence of obstruction, should be considered a candidate for impending obstruction and followed closely for ureteral stent placement.

Adenocarcinoma↗

PubMed1987

[Distant metastases of malignant thyroid cancer. A retrospective study of 892 cases].

In 892 patients with thyroid carcinoma, distant metastases developed in 151 cases, and these were classified according to conventional pathohistological types and--in particular--to the incidence of surgically treatable solitary sites. The aim of the present study was also to investigate whether the histological diagnosis is of value in predicting the pattern of metastatic spread. Distant metastases of anaplastic carcinoma and sarcoma were found most frequently in the lungs (70 out of 81 patients, this is 86%), with 4 cases being solitary tumors. Metastatic spread into the skeleton, however, occurred rarely (14 out of 81 patients, 17.3%), when compared with differentiated carcinoma (64.8%). Moreover, with the exception of 1 case, metastatic growth was not solitary but involved more areas in bone. On the other hand, the well differentiated carcinoma displayed a greater predilection for the metastatic spread to the skeleton: 35 cases of bone involvement were identified in 54 patients with distant metastases (64.8%), and out of these cases, 10 metastases were solitary. Metastatic spread into the lungs occurred less often (30 of the 54 patients, 55.5%) and always displayed a diffuse pattern or involved multiple sites. In some cases, solitary metastases of different histological types were also identified in other organs. Our findings suggest that the pathohistological classification appears to be of use in guiding the clinical approach to a curative extirpation of distant solitary metastases in selected patients.

Humans↗

PubMed1999

Ovarian carcinoma metastatic to bilateral axillary lymph nodes. A case report.

BACKGROUND: Ovarian cancer is a major cause of cancer deaths in women and usually presents with diffuse abdominal disease. Lymph node metastases are common, but axillary lymph nodes are rarely involved. CASE: A 63-year-old woman, initially presenting with abdominal symptoms and massive ascites, underwent optimal cytoreduction followed by intravenous chemotherapy with paclitaxel and carboplatin. The patient subsequently underwent a second-look surgery revealing only microscopically positive disease and then received intraperitoneal chemotherapy with cisplatin. At a follow-up visit, she was found to have bilateral axillary lymph node enlargement. Mammography revealed no lesions in either breast. Fine needle aspiration dissection confirmed the diagnosis of metastatic, recurrent ovarian adenocarcinoma and subsequently axillary lymph node dissection was undertaken. CONCLUSION: Ovarian carcinoma, which usually follows typical patterns of metastatic involvement, can appear in unusual areas.

Axilla↗

PubMed1986

Analysis of the lodgement and extravasation of tumor cells in experimental models of hematogenous metastasis.

This review summarizes our experiments on the metastatic distribution patterns of Yoshida sarcoma and several strains of rat ascites hepatomas. These dissemination patterns cannot be explained entirely by either anatomical-mechanical considerations or by the seed-and-soil hypotheses for metastatic localization. In some experimental situations, anatomical-mechanical factors seem more important, but in others the seed-and-soil hypothesis offers a more compelling interpretation. Lodgement of tumor cells in the microcirculation of different organ vascular beds can occur by three non-exclusive mechanisms: direct attachment to vascular endothelial cells; direct adhesion to exposed vascular basement membrane components or by entrapment in thrombi. Similarly, extravasation can also occur via several mechanisms. The first, involves infiltration of tumor cells into perivascular tissues via their own movement. A second mechanism involves sequestration of tumor cells beneath vascular endothelial cells where they are separated from the blood stream. The third option for extravasation involves 'explosive' displacement in which the blood vessel wall swells as a result of intracapillary growth of tumor emboli causing the vessel to rupture.

Animals↗

PubMed1992

Metastatic potential of human colon cancer cell lines: relationship to cellular differentiation and carcinoembryonic antigen production.

The relationship between cellular differentiation and carcinoembryonic antigen (CEA) production by human colorectal tumor cells and their ability to form hepatic metastases was studied. Eight human colon cancer cell lines were injected into athymic mice using different routes of administration to characterize their metastatic potential. The four poorly differentiated, non or low CEA producing cell lines were poorly metastatic to the liver after intrasplenic injection. After intraperitoneal implantation the same cell lines were highly tumorigenic, and subsequently metastatic to the liver. In contrast, the four moderate to well-differentiated cell lines that produced moderate to high levels of CEA were highly metastatic to the liver following intrasplenic injection. After intraperitoneal implantation they were less tumorigenic, and metastatic to the liver. We conclude that in this system poorly differentiated non or low CEA producing colorectal cell lines have a lower metastatic capacity compared to the well-differentiated high CEA producing colorectal cell lines. These data correlate directly with the pattern of metastatic spread and clinical course observed in patients with these tumors, suggesting that degree of differentiation and level of CEA production may play a role in development of site-specific metastases.

Animals↗

PubMed2005

[Metastatic involvement of the central nervous system in breast cancer: role of herceptin].

The metastatic involvement pattern of breast cancer has been changing in recent years and, in this sense, an increase in the incidence of metastatic involvement of the central nervous system (CNS) is being observed. In this situation, the role that the introduction of new therapeutic agents has must still be defined. In this article, we review the possible role played by treatment with Herceptin in the appearance of metastatic involvements of the CNS.

Antibodies, Monoclonal↗

PubMed1991

The prevalence and location of metastases from ocular melanoma: imaging study in 110 patients.

Ocular melanoma is characterized by an unpredictable clinical course, during which fulminant metastatic disease may occur after a prolonged disease-free interval. The purpose of this study was to determine the pattern of metastatic involvement in this disease. The clinical and radiologic findings in 110 patients with metastatic ocular melanoma were reviewed. The 54 men and 56 women were 24-79 years old (mean, 50 years) when the primary tumor was first diagnosed. Metastases were present in three patients at the time of first diagnosis and occurred in 107 patients 2 months to 36 years later (mean, 52 months). One hundred five patients died between 1 and 38 months after the onset of metastatic disease. Hepatic metastases developed in 101 patients (92%), and in 60 (55%) of these, the liver was the only organ involved initially. Pulmonary parenchymal metastases developed in 34 patients (31%), but in only four of them were metastases confined to the lungs. Twenty-five patients (23%) had bone involvement, mostly affecting the spine. Nineteen patients (17%) had skin or subcutaneous metastases, but in only two of them was this the initial finding. Nodal involvement was shown in 15 patients (14%), almost always associated with extensive hepatic metastases. Brain and adrenal metastases were seen in five and three patients, respectively. Hepatic involvement occurs in almost all patients who develop metastatic ocular melanoma, and the liver is the most common initial site of metastatic involvement. Metastases may develop after a long disease-free interval.

Adult↗

PubMed2006

The "Sentinel Chain": a new concept for prediction of axillary node status in breast cancer patients.

BACKGROUND AND OBJECTIVES: More than half the breast cancer patients with positive sentinel lymph nodes (SLN) do not harbor additional metastases in non-sentinel nodes (NSN). The aim of this study was to identify a subgroup of patients with positive SLNs and negative NSNs, on the basis of tumor involvement patterns in multiple radioactive nodes. METHODS: Between 2000 and 2004, 290 patients with primary invasive breast cancer and clinically negative axillary nodes had a SLN biopsy in our breast unit. Radiotracer was identified intraoperatively in the axilla. All radioactive nodes were removed and radioactivity was measured in each node extracorporeally. Nodes were ranked according to radioactivity, constituting a "Sentinel Chain", and the histopathological status of each node was reported. The different metastatic involvement patterns of the Sentinel Chain were correlated with the metastatic status of the NSNs after axillary dissection. Information was charted in a prospective database. RESULTS: Of 290 patients, 216 (74.5%) had multiple radioactive nodes. Ninety patients (31%) had SLN metastases. Fifty patients had multiple ranked radioactive nodes and positive SLNs. Twenty-five of these patients had a sequential involvement pattern, with tumor-bearing high radioactivity nodes, and uninvolved low-radioactivity nodes. In the 23 of these 25 patients who had axillary dissection, NSN involvement was detected in only one patient (4.3%), whereas in 24 patients with other involvement patterns of the Sentinel Chain, NSN involvement reached 54.2% (p<0.001). CONCLUSION: Tumor-free status of NSN may be predicted using the Sentinel Chain concept in some breast cancer patients with positive SLNs.

Axilla↗

PubMed1982

Radiation therapy for bone metastasis.

Radiation therapy is an important palliative treatment in the management of patients with metastatic bone disease. Excellent results are obtained following radiation therapy to the involved area when generous margins are employed with appropriate megavoltage devices and time-dose-fractionation/protraction. Often an objective response to treatment occurs, as evident by roentgenograms and by pathologic evaluation. Whether the patient's expected life span is relatively short or relatively long, the approach to treatment of bone metastasis must be done within the context of a multidiscipline management. Close cooperation is necessary among radiation oncologists, medical oncologists, orthopedic surgeons, and physiatrists. Radiation therapy for local persistent symptoms relative to bone metastases is an effective technique for achieving long-term control of localized pain without the need for retreatment. Those patients who have a single metastasis with no other evidences of metastatic disease, and who are best treated aggressively, should be differentiated from those patients who have bone metastases as part of a general pattern of metastatic disease where more conservative radiation therapy techniques would be pursued.

Adult↗

PubMed2002

Expression profiling and interferon-beta regulation of liver metastases in colorectal cancer cells.

Liver metastasis is the major cause of death among colorectal cancer patients. Many gene products have been associated with the colon cancer cells' ability to metastasize to the liver, including carcinoembryonic antigen (CEA) and mucins. In this study we examined changes in expression of 384 genes in a model of human colorectal cancer metastasis in nude mice. Using DNA microarrays, we compared expression between MIP-101 cells, a poorly metastatic human colon cancer cell line, with an interferon-beta (IFN-beta) resistant subline of MIP-101 (beta-MIP) that is metastatic to the liver. Treatment of beta-MIP cells with increasing concentrations of IFN-beta caused a reversion to the non-metastatic phenotype. The array data showed down-regulation of genes involved in apoptosis in beta-MIP cells and their return to the MIP-101 pattern upon IFN-beta treatment. Cluster analysis also showed involvement of genes belonging to cell cycle, angiogenesis and invasion pathways. Selected genes were chosen to validate the microarray data by semi-quantitative RT-PCR. Association between gene expression pattern and metastatic phenotype was verified by intra-splenic injection in nude mice. The number of genes examined in this study was small, but carefully selected. Significant changes associated with cell growth and survival were observed, which gave the metastatic cells an advantage to grow in the liver. This information may help identifying new markers for colorectal cancer prognosis as well as aid the development of new therapeutic approaches.

Animals↗

PubMed1996

Uterine adenomatoid tumors: immunohistochemical characteristics with emphasis on Ber-EP4 immunoreactivity and distinction from adenocarcinoma.

Uterine adenomatoid tumors (UATs) may be difficult to distinguish from metastatic adenocarcinoma, particularly in pelviscopic biopsy specimens, myomectomy specimens, or endometrial samplings. This problem may arise because of the infiltration of vacuolated mesothelial cells between fascicles of prominent smooth muscle, which is a characteristic feature in UAT. This diagnostic difficulty has led to inappropriate surgery as reported in the past. Eleven UATs were studied to clarify the differences between these tumors and metastatic adenocarcinoma. Six of the tumors were grossly indistinguishable from leiomyomas. Histologically, the neoplastic mesothelial cells diffusely infiltrated smooth muscle fascicles in all cases, mimicking the pattern of metastatic adenocarcinoma. Immunohistochemical studies using antikeratin and Ber-EP4 antibodies were positive in the mesothelial component in all 11 and nine tumors, respectively, whereas all 11 UATs were negative using antibodies to carcinoembryonic antigen, CD15, TAG-72, and epithelial membrane antigen. Immunoreactivity using Ber-EP4 was focal, membranous, and usually weak, although a strong signal was present in one case. Immunoreactivity using Ber-EP4 (compared with negativity reported for mesothelial proliferations of other sites) may be related to the unique müllerian characteristic of the female peritoneum. Although nonimmunoreactivity for Ber-EP4 favors a diagnosis of UAT over that of adenocarcinoma, Ber-EP4 immunoreactivity does not exclude UAT.

Adenocarcinoma↗

PubMed1999

Identification of semaphorin E gene expression in metastatic human lung adenocarcinoma cells by mRNA differential display.

UNLABELLED: Human lung adenocarcinoma cell lines HAL-8Luc and HAL-24Luc differ in their metastatic potential. HAL-8Luc cells metastasize to lungs when injected either intravenously or intramuscularly. in mice while HAL-24Luc cells do not. The differential display method is used to identify genes differentially expressed between the two cell lines and the findings are extensively discussed. BACKGROUND: Lung cancer is the leading form of cancer in most countries, and metastasis is the main cause of death in oncological patients. The metastatic phenotype of tumor cells is the result of genetic events altering the RNA and protein expression of normal cells. Our objective was to identify genes expressed differentially between metastatic and nonmetastatic human lung adenocarcinoma cells that might be used as a prognostic factor. METHODS: The differential display technique was used to compare the RNA expression patterns distinguishing metastatic (HAL-8Luc) and nonmetastatic (HAL-24Luc) human lung adenocarcinoma cells, two genetically close cell lines. RESULTS: Differential expression of three cDNAs was confirmed by Northern blot analysis. Two sequences corresponding to a putative splicing factor and a proliferation-related factor cDNAs were underexpressed in the metastatic cells relative to the nonmetastatic ones. Interestingly, we found that human semaphorin E mRNA was several fold overexpressed in the metastatic cells. This recently identified gene encodes a protein whose expression has been related to several cell survival mechanisms as well as to immunosuppression. CONCLUSION: Our results point to the relevance of semaphorin E in metastatic spread of human lung adenocarcinoma cells.

Adenocarcinoma↗

PubMed2003

Evolving significance of prognostic markers associated with new treatment strategies in neuroblastoma.

The striking differences in the natural history of clinical subgroups of neuroblastoma (NB), and the evolving therapeutic approaches for each, makes it imperative for prognostic markers to be reevaluated within individual clinical categories. At least one third of NB cases present without distant metastasis and cytotoxic therapy does not alter the natural history. We carried out a retrospective analysis of archived tumor samples. Fifty-seven of these patients had local-regional (LR) NB and were managed conservatively, initially treated with surgery alone. Among the biologic and clinical features analyzed including age, stage, histology, ploidy, MYCN, and 1p36, 1p22, 11q, 14q, 9p and 19q loss of heterozygosity (LOH) in multivariate analysis, diploidy was one of the most significant factors associated with progression-free survival and stage 4 progression. Clonal ploidy heterogeneity was common in LR NB. A predominant near-triploid clonal population was found in most cases of non-progressing LR NB tumors whereas progressing LR NB cases had a predominant diploid clone. We also reviewed the prognostic factors among 84 stage 4 NB cases treated with the N5, N6 or N7 protocols at MSKCC from 1987 to 1999. Traditional markers such as lactate dehydrogenase (LDH), ferritin, age and MYCN status were not prognostic in the univariate analysis. 11q23 and 1p22 LOH were correlated with better survival. These results highlight the evolving significance of prognostic analysis in homogeneous clinical groups undergoing similar treatments. To further characterize the gene expression profile between local-regional and metastatic NB, we carried out Microarray analysis of 41 NB tumors and 12 NB cell lines, using the Affymetrix Genechip Human Genome U95 Set. Distinct gene expression patterns between metastatic and non-metastatic NB tumors have been identified. Validation of these results and further mechanistic studies may shed new light on the biology of metastasis in human NB.

Biomarkers, Tumor↗

PubMed1987

Characterization of an animal model of metastatic colon carcinoma.

Although numerous animal tumor models have been used to study colon carcinoma, few display metastatic properties. We have characterized an animal tumor model that has 3 properties essential for the study of metastasis of colon carcinoma cells: epithelial cell origin; a reproducible pattern of metastatic behavior and the ability to be propagated both in vitro and in vivo to facilitate identification of biochemical correlates of metastasis. The K12/TR cell line was derived from a transplantable colon carcinoma induced by dimethylhydrazine in the BD-1X rat strain. Transmission electron microscopy of K12/TR cells demonstrated junctional complexes, desmosomes and surface microvilli characteristic of gastrointestinal epithelial cells. The epithelial cell origin of K12/TR was confirmed by demonstrating the presence of keratin, a marker of epithelial cells, but not vimentin, a constituent of mesenchymal cells. Secretion of CEA and Ca19-9 antigens by K12/TR cells in vitro was below the sensitivity of the assays (1 ng/ml and 6 U/ml respectively). K12/TR cells produced tumors following s.c. injection into syngeneic BD-1X rats, allogeneic RNU/rnuDF rats and xenogeneic CRL:nu/nuBR mice. Macroscopic lung metastases were observed in animals from all 3 groups. Distal lymph node metastases were more frequent in BD-1X rats than in nude rats or mice. The histological appearances of all tumors and metastases were similar, showing a moderate to poorly differentiated glandular carcinoma. Intrasplenic injections of K12/TR cells in nude mice resulted in liver colonization. Preferential growth of tumor cells at sites of trauma was also observed. The results show that the K12/TR system can be used as a model to study metastasis of colon carcinoma cells and may find utility in the testing of chemotherapeutic agents against metastatic lesions.

Animals↗

PubMed2000

[Ultrasonographic evaluation of metastatic cervical lymph nodes in head and neck cancers].

This study evaluates the use of ultrasonography (USG) to diagnose metastatic cervical lymph nodes. Three-hundred and one lymph nodes were removed from 58 patients with squamous cell carcinomas of the head and neck. None of the patients had received any preoperative treatments for cancer. The lymph nodes were then histopathologically examined: 139 metastatic lymph nodes and 162 non-metastatic nodes were found. USG was then used to evaluate the size, internal echo, and margin of each lymph node. Size was found to be the best criteria for distinguishing metastatic lymph nodes from non-metastatic lymph nodes in all cervical regions (78% accuracy). Superior internal jugular lymph nodes and submandibular lymph nodes larger than 7 mm and mid and inferior internal jugular lymph nodes larger than 6 mm were regarded as metastatic. Internal echoes were classified into five patterns: homogeneous hypoechoic, homogeneous hyperechoic, heterogeneous, eccentric hyperechoic, and centric hyperechoic. Homogeneous hyperechoic and heterogeneous patterns were characteristic of metastatic nodes, while eccentric hyperechoic patterns were characteristic of non-metastatic nodes. Homogeneous hypoechoic patterns were observed in both metastatic and non-metastatic nodes. Regular margins were found in 81% of the metastatic nodes. Of the 22 lymph nodes with irregular margins, however, 91% were metastatic. Evaluations using a combination of USG and clinical feature criteria were compared with evaluations using only thickness as a criterium. Although thickness is the single most important factor in diagnosing metastatic nodes, the combination of USG and clinical feature criteria improved the accuracy of diagnosis to 83%. Thus, diagnostic methods involving a combination of several criteria are more accurate than methods involving only a single criterium.

Carcinoma, Squamous Cell↗