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Results for “Metastatic patterns”

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PubMed2004

Wide metastatic spreading in infiltrating lobular carcinoma of the breast.

The aim of this study was to determine whether the metastatic potential of breast cancer could be related to phenotypic characteristics of the tumour. Therefore, we compared the metastatic patterns of invasive lobular (ILC) and ductal (IDC) carcinomas. In ILC, we also analysed this pattern according to the histological subtype of the primary and the E-cadherin (EC) expression level. Metastatic ILC cases (n=96) were retrospectively analysed and classified into classical, alveolar, solid, tubulo-lobular, signet ring cells or pleomorphic subtypes. Anatomical distribution of metastases was detailed for every patient and compared with that registered for IDC (n=2749). Immunostaining of EC (HECD1 antibody) was performed in 82 cases. Histologically, 78 of the 96 cases (81%) corresponded to classical ILC. The pleomorphic subtype was observed in 14 cases (15%), a rate that was higher than that expected. Others corresponded to alveolar (2 cases), signet ring cell (1 case) and solid (1 case) subtypes. EC was undetectable in 72/82 cases (88%). The rate of multiple metastases was higher in ILC (25.0%) than in IDC (15.8%) (P=0.016). Metastases were found more frequently in ILC than in IDC in the bone (P=0.02) and/or in various other sites (peritoneum, ovary, digestive tract, skin em leader ) (P<0.001). In ILC, no significant link was found between the localisation(s) of metastases, the histological subtype and the EC status in the primary. In conclusion, in breast carcinomas, the frequency of multiple metastasis was found to be higher in ILC than IDC. This fact may be related to the phenotypic trait of discohesive small cells which characterises ILC. EC loss, observed in most cases of ILC, may result in alterations in cell-cell adhesion and a preferential growth at metastatic sites. A high rate of pleomorphic tumours was observed in the group of metastatic ILC, but the pattern of metastatic site(s) was not related to the histological subtype of the primary.

Breast Neoplasms↗

PubMed1998

Growth, metastasis, and invasiveness of Drosophila tumors caused by mutations in specific tumor suppressor genes.

More than 50 genes have been identified in Drosophila by loss-of-function mutations that lead to overgrowth of specific tissues. Loss-of-function mutations in the lethal giant larvae, discs large, or brain tumor genes cause neoplastic overgrowth of larval brains and imaginal discs. In the present study, the growth and metastatic potential of tumors resulting from mutations in these genes were quantified. Overgrown brains and imaginal discs were transplanted into adults and beta-galactosidase accumulation was used as a marker to identify donor cells. Mutations in these three genes generated tumors with similar metastatic patterns. For brain tumors, the metastatic index (a measure we defined as the fraction of hosts that acquired secondary tumors normalized for the amount of primary tumor growth) of each of the three mutants was similar. Analysis of cell proliferation in mutant brains suggests that the tumors arise from a population of several hundred cells which represent only 1-2% of the cells in third instar larval brains. For imaginal disc tumors from lethal giant larvae and brain tumor mutants, it is shown for the first time that they can be metastatic and invasive. Primary imaginal disc tumors from lethal giant larvae and brain tumor mutants formed secondary tumors in 43 and 53% of the hosts, respectively, although the secondary tumors were, in general, smaller than the secondary tumors derived from primary brain tumors.

Animals↗

PubMedDate not supplied

Lymph node imaging: from conventional radiology to diagnostic imaging.

From Herophilus, Aristotle in the 3rd century BC, Aselli, Pecquet, Mascagni to Jossifow and Rouviere the lymphatic system was investigated. Kinmonth and Wallace were the first to study it with lymphangiography. Mediastinal lymph nodes were poorly visualized in high contrast radiography before the seventies; subsequently with the high voltage technique, xerography and signs from mediastinal lines they were better identified. However these procedures were replaced by CT, with which even lymph nodes less than 0.5 cm in size, are recognized. The differentiation between normal and pathologic lymph nodes is based on dimensional, morphologic and densitometric criteria. CT is able to identify typical patterns of inflammatory, systemic and metastatic lymph nodes. On lymphography a great number of signs as gross and dense dotting, foaming, chipping and lacunae are identified, which allow the differentiation of inflammatory, systemic and metastatic patterns. On sonography some nodal characteristics are evidenced as the round shape, hypoechogenicity, absence of hyperechoic medullary line. CT has replaced lymphangiography in the study of abdominal lymph nodes.

Humans↗

PubMed1991

An evaluation of differences in prognosis, recurrence patterns and receptor status between invasive lobular and other invasive carcinomas of the breast.

One-hundred-and-seventy-one patients with invasive lobular carcinomas have been matched with 342 patients with non-lobular invasive carcinomas for lymph node stage, tumour differentiation and patient age on a one to two basis. The two groups were investigated for differences in prognostic factors, survival, disease-free interval, metastatic patterns, receptor status, response to endocrine therapy after distant metastases and bilateral cancer rates. Patients with lobular carcinomas survived significantly longer than patients with carcinomas of no specific type, particularly in survival from the time of diagnosis of distant metastases; lobular carcinomas more often responded to endocrine treatment for systemic disease. Lobular cancers had a significantly higher rate of local recurrence, particularly after treatment by excision and breast irradiation. No differences were found between the two groups with respect to regional or distant recurrence rates, distant organ involvement patterns, distant metastatic free intervals and receptor status. Bilateral cancer was more frequent in patients with lobular carcinoma.

Breast Neoplasms↗

PubMed2004

Metastatic carcinoma of the breast with tubular features: differences compared with metastatic ductal carcinoma of no specific type.

AIMS: To compare the metastatic pattern at presentation and the prognosis with metastases of 48 patients with carcinomas with tubular features (45 tubular mixed and three pure tubular) and 302 patients with tumours of ductal of no special type (DNST). MATERIALS AND METHODS: We carried out a retrospective study from a prospectively maintained database of all patients who developed metastatic disease from carcinoma of the breast in Nottingham, U.K., since 1997. We recorded site of first presentation with metastatic disease, radiological features, histological features and characteristics of the primary tumour. RESULTS: The group of patients with tubular features were older at metastatic presentation (63.9 years vs 59.6 years; P=0.012), had a longer disease-free interval (87 months vs 34 months: P<0.001) and a longer survival with metastases (P<0.002). This group were less likely to have liver metastases (23% vs 41%; P=0.028), in particular multiple liver metastases (50% vs 71%; P=0.015) than the patients with DNST. Other factors known to be associated with prolonged survival, such as low histological grade of the primary invasive tumour and positive oestrogen receptor (ER) status, were more common in the group of patients with tumours with tubular features (Grade 1: 33% vs 3%; Grade 2: 42% vs 25%; Grade 3: 25% vs 72%; P<0.001), (ER positivity 76% vs 52%; P=0.009). When patients with grade 2 tumours were compared, the age at metastatic presentation, disease-free interval and the presence of multiple liver metastases were still significantly different between the two groups. CONCLUSION: Patients with metastatic breast carcinoma with tubular features have a longer survival with metastases than patients with metastatic DNST carcinoma. This improved survival can be explained by better well-recognised prognostic features, such as metastatic site pattern, histological grade, ER status and disease-free interval.

Adenocarcinoma↗

PubMed2002

Optically imageable metastatic model of human breast cancer.

We report an optically imageable orthotopic metastatic nude mouse model of the human breast cancer MDA-MB-435 expressing green fluorescent protein (GFP). We demonstrate fluorescent imaging of primary and metastatic growth in live tissue and in intact animals. Fragments of tumor tissue expressing GFP were sutured into the pocket in the right second mammary gland. Tumor tissue was strongly fluorescent, enabling whole-body imaging of tumor growth by week 5. Neovascularization of the primary tumor was also visualized by whole-body imaging by contrast of the vessels to the fluorescent tumor. At autopsy, the MDA-MB-435-GFP was found to have metastasized to various organs, including the lung in 55% of the animals, the lymph nodes in 15% of the animals including axillary nodes, and the liver in 10% of the animals. These metastases could be visualized in fresh tissue by fluorescent imaging. Detailed fluorescence analysis visualized extensive metastasis in the thoracic cavity and the lymphatic system. Large metastatic nodules in the lung involved most of the pulmonary parenchyma in all lobes. Lymph node metastasis was found mainly in the axillary area. In the liver, fluorescent macroscopic metastatic nodules were found under the capsule. The metastatic pattern in the model thus reflected clinical metastatic breast cancer and provides a powerful model for drug discovery for this disease.

Adult↗

PubMed1997

Macrophage colony-stimulating factor gene transduction into human lung cancer cells differentially regulates metastasis formations in various organ microenvironments of natural killer cell-depleted SCID mice.

We investigated whether local production of macrophage colony-stimulating factor (M-CSF), responsible for migration and activation of monocytes/macrophages at a tumor growth site, affected the metastatic pattern of lung cancer. For this, highly metastatic human squamous (RERF-LC-AI) or small (H69/VP) cell lung carcinoma cells were transduced with the human M-CSF gene inserted into pRc/CMV-MCSF to establish M-CSF-producing clones (MCSF-AI-9-18, MCSF-AI-9-24, and MCSF-VP-5). M-CSF gene transduction had no effect on the expression of surface antigen or on in vitro proliferation. After s.c. injection into SCID mice, the growth rates of M-CSF-producing cells were slower than those of parent or mock-transduced cells. In the metastatic model in SCID mice depleted of natural killer cells, RERF-LC-AI cells formed metastases mainly in the liver and kidneys, whereas H69/VP cells metastasized mainly to the liver and systemic lymph nodes. The numbers of metastatic colonies of MCSF-AI-9-18 and MCSF-AI-9-24 cells in the liver but not the kidneys were significantly reduced. The development of lymph node metastases of MCSF-VP-5 cells was also less than that of parent or mock-transduced cells. Treatment of SCID mice with anti-human M-CSF antibody resulted in a significant increase in liver metastases of their M-CSF gene transfectants. No significant differences were observed in the distributions in mice or in the in vitro invasive potentials of MCSF-AI-9-18 cells and Neo-AI-3 cells. These findings indicate that the antimetastatic effect of M-CSF may be specific to particular organs, suggesting the influence of heterogeneity of organ microenvironments on the metastasis of lung cancer.

Animals↗

PubMed2002

Heterotopic implantation alters the regulation of apoptosis and the cell cycle and generates a new metastatic site in a human pancreatic tumor xenograft model.

Differences in growth and in response to antineoplastic drugs between s.c. and orthotopically implanted tumors in nude mice and between the primary tumor and the metastases in human tumors suggest that implantation site may alter the molecular regulation of tumor cells. We assessed the influence of implantation site on cell cycle and apoptotic regulation and the possible contribution of the implantation site in directing the choice of metastatic site by comparing the behavior of tumor aliquots of two human pancreatic xenografts (NP18 and NP9) implanted in the organ where the tumor grows (orthotopically), in heterotopic sites (the site of metastases (liver), and in nonmetastatic sites (subcutis and colon). We observed that implantation site changes tumor growth by altering apoptotic or cell cycle regulation in a tumor-specific manner. In the NP18 tumor it occurs by altering apoptotic induction and activation of the Bad/Bcl-XL/caspase-3 pathway through AKT and Erk regulation, but in the NP9 tumor by changing the activation and/or expression of the proteins that regulate the cell cycle (Erk, PCNA, and cyclin B1). We also observed that implantation site alters the metastatic pattern of the NP9 tumor, originating a new metastatic site.

Animals↗

PubMed2004

Orthotopic transplantation models of pancreatic adenocarcinoma derived from cell lines and primary tumors and displaying varying metastatic activity.

OBJECTIVE: To establish a series of clinically relevant orthotopic transplantation models of human pancreatic adenocarcinoma from both cell lines and primary tumors under uniform experimental conditions. METHODS: Ten pancreatic cancer cell lines and 12 primary tumors were orthotopically transplanted in SCID mice. The cell lines and xenografts were characterized for K-ras, BRAF, p53, p16, and DPC4 aberrations employing direct sequencing, immunohistochemistry, and Western blotting. RESULTS: All xenografts showed high intrapancreatic tumorigenicity and extensive local tumor growth, and each showed a unique behavioral and genetic profile. Tumor characteristics were retained during serial passaging. The cell line-derived xenografts represented the entire expected range of histologic differentiation. Although the overall metastatic rate was moderate to high, the metastatic pattern varied; 4 cell lines showed a high metastatic rate to the liver. The primary tumor-derived xenografts retained their similarity to the corresponding original donor tumors with regard to histologic presentation and biologic behavior. K-ras, p53, p16, and DPC4 aberrations were revealed in 80%, 70%, 50%, and 40% of cell lines and 100%, 33%, 75%, and 58% of primary tumor derived xenografts, respectively. No BRAF mutations were present. The metastatic behavior of the xenografts was significantly associated with the degree of histologic differentiation, number of genes altered, and p53 status. CONCLUSIONS: The new models reflected the wide range of patho-biological features and genetic alterations that characterize human pancreatic cancer and may be used collectively or selectively as a markedly improved in vivo tool for preclinical and molecular studies of pancreatic cancer.

Adenocarcinoma↗

PubMed1999

[Correlation of histology of the primary tumor with liver metastases in colorectal carcinoma].

The histology of colorectal tumors was correlated with the presence of liver metastases in a retrospective study performed on 179 patients who were autopsied between 1975 and 1990. For the analysis of metastatic patterns, 116 cases with at least one distant metastatic site were selected. A distinct relationship between mucin expression of colorectal tumors and liver involvement was found. Pure adenocarcinomas and their papillary variants showed the highest affinity to the hepatic tissue regarding the frequency as well as extent of involvement. A subtotal replacement of the liver by metastases was restricted to these two variants. An extracellular mucin component was associated with a lower frequency of liver involvement and a tendency to solitary or oligotopic metastases. Ten cases of signet ring cell carcinomas had no metastases in the liver. The results described here for colorectal cancers are similar to those previously reported for gastric cancer. The therapeutic implications were discussed. A detailed link between these clinical findings and the results found at the level of molecular biology is yet to be determined.

Adult↗

PubMed2000

Differences of vascular endothelial growth factor (VEGF) expression between liver and abdominal metastases from colon cancer. Implications for the treatment with VEGF inhibitors.

The vascular endothelial growth factor (VEGF) plays a central role in promoting angiogenesis, and it is the target of innovative anti-cancer therapies. In colorectal carcinomas, differences in the VEGF expression have been found between the primary tumor and its metastases. We postulated that differences in the VEGF expression may also exist between liver and abdominal metastases from colon cancer. Consecutive colon cancer patients with liver or abdominal metastases were considered eligible for the study. Biopsies had to be performed before chemotherapy and the VEGF analysis were conducted through immunohistochemistry. The staining results were correlated to the metastatic pattern. The study population consisted of 41 patients with a metastatic site in the liver in 19 patients and the abdomen in 22 patients. A positive VEGF staining was found in 19 of the 41 metastatic samples (46%). Cases with positive VEGF expression were found more frequently in abdominal (15 out of 22 patients; 68%) than in liver metastases (4 out of 19 patients; 21%). Also, the degree of VEGF immunoreactivity was significantly higher in abdominal than in liver metastases. Evidence is supported that the VEGF expression may be different between colon cancer metastatic sites. The efficacy of anti-VEGF treatments may depend on the VEGF expression status, and this finding deserves further investigation.

Abdominal Neoplasms↗

PubMed1984

Mesenchymal chondrosarcoma of the kidney.

A case of mesenchymal chondrosarcoma of the kidney, with osseous metastases, is presented in this article, and the clinical, radiologic, and histopathologic features of this uncommon neoplasm are discussed. The addition of this case to those previously reported in the literature brings the total number of reported cases of mesenchymal chondrosarcoma of extraskeletal origin to 42. None of the previously reported cases originated from the kidney. The metastatic pattern of this case illustrates the propensity of mesenchymal chondrosarcoma to metastatize to unusual locations.

Adult↗

PubMed1994

[The radiodiagnosis of bone metastases from melanoma].

The records of 3,795 cases of malignant melanoma treated at the INT (Milan) from 1975 to 1992 were reviewed. Histologic confirmation was obtained in all cases. Thirty-one patients (0.82%) with solitary or multiple skeletal metastases were identified. The review of conventional films, tomograms, CT, MR and bone scintigraphy images enabled us to detect 120 single bone lesions. The X-ray features were divided into two groups according to typical and atypical skeletal lesions. Typical bone metastases are osteolytic (87.5%), with medullary origin (91.6%), and they cannot be distinguished from other osteolytic metastases on the basis of imaging criteria alone. Lesion growth causes cortical erosion and destruction (46.6%), pathologic fractures (22.5%) and soft tissue involvement (12.5%). Lytic areas usually have ill-defined margins. Clear-cut outline is an uncommon finding. Atypical skeletal metastases exhibit a mixed osteolytic-osteoblastic pattern (10%), which is hardly ever completely osteoblastic (2.5%). Other unusual metastatic patterns include intense trabecular rarefaction with no detectable single lesion (3.3%), the presence of a well-defined sclerotic rim and periosteal reaction (12.5%). Atypical growth may cause extensive cortical destruction and periosteal production resembling osteogenic osteosarcoma. The various imaging methods show that conventional radiology has relatively poor sensitivity because of anatomical reasons, while MRI is the most sensitive method to detect skeletal localizations. Treatment changes the radiologic patterns of the lesions: recalcification, sclerotic rim, periosteal reaction are common response patterns. Finally, in spite of the above limitations, conventional radiology remains the method of choice to assess lesion evolution during the follow-up.

Bone Neoplasms↗

PubMed1986

Cardiac angiosarcomas. A review and a case report.

Forty-five cases of cardiac angiosarcomas were reviewed, and the data were compared with those of a 1968 review of 41 other cases which revealed these tumors to be typically located within the right atrium as large symptomatic masses and to be rapidly fatal, with the diagnoses usually determined only at autopsy. The relationship of these tumors to Kaposi's sarcoma was also examined. The findings paralleled those of the previous review. Additionally, the following points emerged: With the aid of newer imaging techniques, localization, biopsy diagnosis and resection of the atrial tumors are now being achieved more often, with some improvement in survival. Like angiosarcomas of other organs, atrial angiosarcomas exhibit highly variable histologic patterns, which often overlap those of Kaposi's sarcoma, and may also present metastatic patterns simulating widespread Kaposi's sarcoma or malignant melanoma. In reported cases of classical, endemic, or epidemic Kaposi's sarcoma, cardiac lesions are uncommon and typically are small, asymptomatic, restricted to the epicardium/or pericardium and, thus, are clearly different, both clinically and pathologically, from the atrial tumor group. The justification for designating cases of the latter group as "primary cardiac Kaposi's sarcoma" is open to debate. A case report illustrates many of the above points.

Adult↗

PubMedDate not supplied

Duodenal obstruction from isolated breast cancer metastasis: a case report.

Metastatic involvement of the upper gastrointestinal tract from breast cancer has been reported in autopsy series as occurring in more than 15% of patients, usually associated with extensive systemic spread; clinical manifestations from such metastases have been described in less than 1% of cases. Lobular infiltrating carcinoma seems to have a different metastatic pattern than the ductal type, with an apparent predilection for the gastrointestinal tract. Metastatic presentation as an isolated intestinal obstruction without other signs of metastatic spread is extremely rare. We present a case of isolated duodenal metastasis from breast cancer, associated with intestinal obstruction, as the first sign of metastatic spread.

Breast Neoplasms↗

PubMed1999

The back door: venous-mediated metastasis into cervical lymph nodes as an alternative metastatic pathway for oropharyngeal squamous cell carcinoma.

Circulating lymphocytes may home to lymph nodes (LNs) via paracortical postcapillary venules, high-endothelial venules (HEVs) that recognize circulating lymphocytes, enabling them to migrate into nodal cortical/paracortical regions. Our goal was to find any histologic, immunohistochemical, or in vitro evidence to support the hypothesis that squamous cell carcinoma (SCC) may gain access to LNs via an alternative venolymphatic pathway. Slides from 67 neck dissections with SCC were studied. Standard criteria for lymphatic-mediated metastasis were used; criteria for evidence ofvenolymphatic metastasis were tumor nests localized to the paracortical regions, directly contiguous to HEVs but not marginal sinuses. Cases in which LN architecture was obliterated by metastases were excluded. A modified Stamper-Woodruff assay, which assesses HEV binding, incubated cell lines from oral carcinomas and lung adenocarcinomas with fresh frozen LN sections. Double-blinded cell counts were performed by two observers and analyzed by Student's t test. Immunohistochemical examination was undertaken on 19 paraffin-embedded cases with the monoclonal antibody, MoAb CD44v6, to discover whether expression of this adhesion molecule correlated with metastatic pattern. Twenty-nine cases (66%) revealed evidence only for the LN route of metastasis; 4 cases (9%) were classified as venolymphatic metastasis; 11 cases (25%) showed evidence for both pathways. The Stamper-Woodruff assay confirmed that SCC cells preferentially bound to HEV within cervical LN sections more than did adenocarcinoma cells (P = .02). Strong staining to MoAb CD44v6 was seen in 18 (95%) of 19 SCCs with a membranous pattern. Occasionally, CD44v6 highlighted tumor emboli adjacent to HEVs, but no overall correlation could be made between CD44v6 expression and pattern of spread. Tumor metastasis via lymphatic channels is the predominant mode of metastatic spread, but the venolymphatic route is a plausible alternative pathway. The preferential attachment of SCC cells to HEVs supports this theory.

Cell Adhesion↗

PubMed1990

Incidence of thyroid cancer in Norway 1970-1985. Population review on time trend, sex, age, histological type and tumour stage in 2625 cases.

In the Norwegian population, a total of 1977 females and 648 males had a diagnosis of thyroid cancer and were reported to the Cancer Registry during 1970-85. Most of the cases (98%) were histologically or cytologically confirmed, and 141 cases were diagnosed at autopsy (5.4%). Of the patients with information available, 13% had not been subjected to radical surgery. The actual number and annual incidence rate of thyroid cancer increased during the period, especially among females, although a possible levelling off was observed at the end. The frequency of papillary carcinoma clearly increased with time, and tumours were more often localized at presentation in later years. Improved detection of smaller tumours and differences in histopathological judgement may in part explain these results, but our findings are so notable that etiological factors must also be accounted for and researched. Associations between sex, age, histology and stage were further studied in a multivariate log-linear model. The results confirm the importance of sex and age when exploring the observed incidence pattern and also show that various histological types are unique with respect to metastatic patterns, when confounding factors have been adjusted for.

Adolescent↗

PubMed2005

Analysis of paired primary lung and lymph node tumor cells: a model of metastatic potential by multiple genetic programs.

BACKGROUND: The current paradigm of metastasis proposes that rare cells within primary tumors acquire metastatic capability via sequential mutations, suggesting that metastases are genetically dissimilar from their primary tumors. We tested this hypothesis by examining the molecular differences, if any, between primary tumor cells and matched lymph node metastatic cells in human non-small-cell lung carcinoma specimens. METHODS: We performed transcriptional profiling studies on malignant cells from 11 pairs of stage III tumors and their tumor-positive lymph nodes using multiple, complementary analytic techniques. To confirm the overall validity of microarray data, we used real-time polymerase chain reaction. RESULTS: The molecular signature of nodal metastasis was a composite of two paradoxical, but not mutually exclusive, expression patterns: metastatic cells are: (1) different from their primary tumor cells based on a few genes and (2) genetically similar, overall, to their primary tumor cells. Consequently, we found a 27-gene subset sufficient to differentiate nodal metastatic cells from primary tumor cells. CONCLUSIONS: Thus, we concluded that a more accurate model of metastatic potential is based on a global primary tumor expression pattern along with the appearance of distinct metastatic variants. The 27-gene signature differentiating primary tumors from their metastatic cells may define non-small-cell lung carcinoma nodal metastatic potential.

Carcinoma, Non-Small-Cell Lung↗