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PubMed1999

Comparison of losses of heterozygosity and replication errors in primary colorectal carcinomas and corresponding liver metastases.

In order to investigate genetic alterations specific to liver metastases of colorectal carcinomas, losses of heterozygosity and replication errors have been compared in 15 cases of primary colorectal carcinoma and in the corresponding metastatic liver tumours. Fifteen microsatellite markers located on 13 different chromosomal arms were used in the study. The LOH patterns of the primary and the metastatic tumours were identical in eight cases and showed differences in seven cases. Areas of deletion predominantly or completely common to the colorectal and the metastatic tumour were detected on chromosomes 5q, 8p, 17p, 18q, and 22q. Preferential loss in metastatic tumours was observed on chromosomal arm 3p. Replication errors were found in four primary tumours and in three of the corresponding secondaries. A replication error phenotype specific to a metastasis was not observed.

Adult↗

PubMed2005

The gene expression signatures of melanoma progression.

Because of the paucity of available tissue, little information has previously been available regarding the gene expression profiles of primary melanomas. To understand the molecular basis of melanoma progression, we compared the gene expression profiles of a series of nevi, primary melanomas, and melanoma metastases. We found that metastatic melanomas exhibit two dichotomous patterns of gene expression, which unexpectedly reflect gene expression differences already apparent in comparing laser-capture microdissected radial and vertical phases of a large primary melanoma. Unsupervised hierarchical clustering accurately separated nevi and primary melanomas. Multiclass significance analysis of microarrays comparing normal skin, nevi, primary melanomas, and the two types of metastatic melanoma identified 2,602 transcripts that significantly correlated with sample class. These results suggest that melanoma pathogenesis can be understood as a series of distinct molecular events. The gene expression signatures identified here provide the basis for developing new diagnostics and targeting therapies for patients with malignant melanoma.

Biopsy↗

PubMed1994

Association of immunohistochemical staining for p53 with metastatic progression and poor survival in patients with renal cell carcinoma.

BACKGROUND: Mutations of the p53 gene have been found in many types of human tumors. In some tumors, p53 gene mutations are associated with advanced disease and poor prognosis. There is wide variation in the reported incidence of p53 mutation in renal cell carcinoma, and its prognostic significance for this tumor is unknown. PURPOSE: This retrospective immunohistochemical study was designed to examine associations between p53 immunostaining and histologic type, tumor grade, clinical behavior, and survival. METHODS: Paraffin-embedded nephrectomy specimens collected from 1978 through 1986 from 175 patients were immunostained for p53 using the D07 monoclonal antibody. Positive staining for p53 has been linked to the accumulation of mutant p53 protein. Thirteen specimens of concurrent metastatic lesions were available from 11 primary cases. Clinical follow-up information was available on 164 patients. RESULTS: Immunostaining for p53 suggested the presence of p53 mutation in 49 (28%) of 175 renal tumors studied. Staining was associated with high tumor grade and stage but not with cell type or histologic pattern. Eleven (85%) of 13 metastatic lesions stained positively for p53, versus only four (36%) of the 11 paired primary tumors. Immunostaining for p53 was strongly associated with poor survival among patients without distant metastases at presentation. In this group, 10-year disease-specific survival was 78% for patients with nonstaining tumors versus 48% for those with p53-positive tumors (P < or = .003). There was an 87% 10-year disease-specific survival rate for patients with nonstaining Robson stage 1 tumors versus a 62% 10-year survival rate for patients with p53-positive Robson stage 1 tumors (P < .01). Multivariate analysis showed p53 immunoreactivity to be an independent predictor of survival for patients with nonmetastatic renal cell carcinoma, whereas tumor grade was not. CONCLUSIONS: Positive p53 immunostaining in renal cell carcinoma is associated with metastatic disease and poor survival in patients with early-stage disease. IMPLICATIONS: In renal cell carcinoma, mutations of the p53 gene may allow or contribute to the acquisition of metastatic potential.

Adult↗

PubMedDate not supplied

MR imaging during arterial-portography (MR-AP) in the detection of hepatic tumor: comparison with CT-AP.

This study was undertaken to compare the detection rate of hepatic space occupying lesion (SOL)s between computed tomography during arterial portography (CT-AP) and magnetic resonance imaging during arterial portography (MR-AP) and the differences in time intensity curve on MR-AP between HCC, metastatic tumor, FNH, and hemangioma. We performed CT-AP and MR-AP in 17 patients including 14 cases of HCC and one each of metastasis, FNH, and hemangioma. MR-AP was performed by Turbo-FLASH sequence. There was no statistically significant difference between CT-AP and MR-AP in detecting satellite lesions in terms of smallest diameter and number of flow defects (p > 0.05). Hemangioma showed rapid enhancement after the first pass and, consequently, the same enhancement as the hepatic parenchyma. MR-AP was comparable to CT-AP in the detection of hepatic SOLs. Hemangioma showed an enhancement pattern different from those of HCC, metastatic tumor, and FNH, which showed patterns similar to each other.

Carcinoma, Hepatocellular↗

PubMed1986

Differential expression of intermediate filament proteins in metastatic and nonmetastatic variants of the BSp73 tumor.

The pattern of intermediate filament protein expression was studied in tumor cell variants of the BSp73 spontaneous rat adenocarcinoma of the pancreas exhibiting distinct morphology and metastatic phenotype. The non-metastasizing AS cells which adhere and spread on a solid substrate express only the vimentin type mesenchymal intermediate filament protein. The ASML metastatic cell variant which adheres but does not spread on the substrate expresses a complex pattern of cytokeratins characteristic of the adenocarcinoma of the pancreas and a low level of vimentin. The differences in the expression of the intermediate filament proteins between the variants were also reflected at the level of the corresponding mRNAs as revealed by RNA blot analysis with complementary DNA clones specific to vimentin and the acidic as well as the basic cytokeratin subfamily. When the two cell variants were cultured for 72 h in suspension culture on nonadhesive substrata the AS cells responded with a marked reduction in their vimentin synthesis. The ASML variant cells which are characterized by a round configuration in both monolayer and suspension culture continue to synthesize the same intermediate filament proteins under both culture conditions. The relationships among environmental conditions that affect cell shape and contacts, the shifts in the expression of intermediate filaments, and the metastatic property of tumor cells are discussed.

Adenocarcinoma↗

PubMed1977

The prognostic significance of pelvic lymph node morphology in carcinoma of the uterine cervix.

Pelvic lymph nodes from 80 patients with primary invasive cervical cancer undergoing radical hysterectomy and pelvic lymphadenectomy were evaluated morphologically. Six to 25 (mean 14) lymph nodes from each patient were examined histologically and classified as follows: lymphocyte preominant, germinal center predominant, unstimulated, or lymphocyte depleted. Tumors were classified according to their primary cell type: large cell non-keratinizing, keratinizing squamous cell, small cell, and adenocarcinoma. There was no direct relationship between lymph node morphology and patient age, lesion size, or tumor cell type. A lymphocyte predominant nodal pattern was associated with a statistically significant decrease in lymph node metastases, and tumor recurrence, and an increase in patient survival. In contrast, patients with a lymphocyte depleted nodal pattern had a high incidence of metastatic disease and tumor recurrence, and a decreased survival. Patients with lymph nodes showing an unstimulated or germinal center predominant pattern had an intermediate incidence of nodal metastases and tumor recurrence. These findings suggest that regional lymph nodal morphology may be of prognostic significance in patients with invasive carcinoma of the uterine cervix.

Adenocarcinoma↗

PubMed2005

Vascular flow patterns of hepatic tumors in contrast-enhanced 3-dimensional fusion ultrasonography using plane shift and opacity control modes.

OBJECTIVE: This study was conducted to determine whether contrast-enhanced 3-dimensional (3D) fusion ultrasonography with combined use of the plane shift and opacity control modes can serve as a useful tool for identifying the vascular characteristics of hepatic tumors in 3D perspective. METHODS: Contrast-enhanced 3D fusion ultrasonography was performed in 31 patients with hepatic tumors after the intravenous injection of contrast media. The shapes, courses, and distributions of tumor vessels, displayed in 3D perspective, were examined to identify the characteristic vascular flow patterns of various tumors. Images before and after contrast media administration were compared for evaluation of the effectiveness of contrast enhancement with regard to tumor diameter for various types of tumors. The images were interpreted in a blinded manner by 3 physicians specializing in abdominal ultrasonography, and vascular flow patterns were determined on the basis of consensus. RESULTS: The characteristic vascular flow patterns observed in hepatocellular carcinomas are reticular flow within the tumor and flow showing a ringlike distribution surrounding the tumor. Metastatic tumors show a vascular flow pattern running between adjacent tumor nodules, and hemangiomas show localized nodular flow at the tumor margins. Contrast enhancement was found to be useful for showing the vascular flow patterns in small hepatocellular carcinomas and hemangiomas. CONCLUSIONS: Contrast-enhanced 3D fusion ultrasonography makes it possible to display images combining the plane shift and opacity control modes to show tumor vessels, including minute vascular flow within hepatic tumors, in 3D perspective and to identify tumor-specific vascular flow patterns.

Adult↗

PubMed1985

Patterns of metastasis and natural courses of breast carcinoma.

Breast carcinoma is known to metastatize to all organs. In order to understand the patterns of spread and natural courses, this review summarizes detailed studies of patients with various stages of the disease. After treatment of early breast carcinoma (stage I, II, and some III), the recurrent lesion can be classified as local, regional, distant, or combinations thereof. The sites of dissemination of patients presenting with stage IV disease and of those who had autopsy after diagnosis of breast cancer are presented for comparison. Clinicopathological factors that influence the relative incidence, specific site, subsequent event, and prognosis of recurrent and metastatic breast cancers are discussed.

Adult↗

PubMed2004

Expression pattern of chemokine receptor 6 (CCR6) and CCR7 in squamous cell carcinoma of the head and neck identifies a novel metastatic phenotype.

Squamous cell carcinoma of the head and neck (SCCHN) metastasizes predictably to cervical lymph nodes, with low rates of distant metastases. Tumor cells can express various receptors that facilitate such metastatic spread to lymph nodes and other nonlymphoid organs. Chemokine receptors (CCR), normally expressed on lymphocytes, control immune and inflammatory cell migration, providing a link between innate and adaptive immunity. Chemokine receptor expression was evaluated in SCCHN, using paired primary and metastatic tumors cell lines, and paired primary and metastatic biopsies from the same patients. Quantitative reverse transcription-PCR showed a consistent pattern of CCR6 down-regulation and up-regulation of CCR7 in metastatic cells and tissues. Chemotaxis assays, ligand-induced receptor down-regulation, and specific antibody blocking experiments supported the quantitative reverse transcription-PCR results, indicating that these surface receptors were functional on metastatic tumor cells. Cells derived from a highly metastatic mouse model of SCCHN were used to confirm CCR7 up-regulation in tumor cells with higher metastatic potential. CCR6 down-regulation is consistent with its decreased expression in cells emigrating from peripheral mucosal sites, whereas CCR7, important for homing of immune cells to secondary lymphoid organs, was significantly up-regulated. Thus, CCR6, CCR7, and their ligands, normally important in controlling immune cell trafficking in response to inflammatory stimuli, may have an important role in determining the metastasis of SCCHN cells in vivo.

Carcinoma, Squamous Cell↗

PubMedDate not supplied

Evaluation of Ki-67 and p53 expression in primary and repeated liver metastases of GISTs.

There has been little research evaluating changes related to tumor cell proliferation between primary and metastatic tumors of gastrointestinal tumors in the same case. We herein report the case of a 50-year-old woman with a gastric gastrointestinal stromal tumor (GIST), who developed metastatic liver tumors three times in the 7 years after proximal gastrectomy for GIST. The primary and all the metastatic liver tumors, except the second, showed fascicular/storiform architecture and the short spindle cell type. The diffuse epithelioid cell proliferation was observed in the second metastatic liver tumor. Although the immunostaining pattern with respect to GIST differentiation markers had been preserved in the primary tumor as well as in all of the metastatic tumors, the latter showed weaker positivity of both Ki-67 and p53 than the primary GIST. The primary tumor showed diffuse positive p53, and the highest value of Ki-67 labeling index (LI) among them. The metastatic liver tumors showed focal, negative or sporadic positive appearances of p53, however, Ki-67 LI were scattering among them. Immunohistochemical assessment of Ki-67 LI and p53 might be useful for evaluating changes related to tumor cell proliferation between primary and metastatic tumors of GISTs.

Biomarkers, Tumor↗

PubMedDate not supplied

Identifying a metastatic choroidal tumor: a case study.

Amelanotic lesions of the eye are more commonly seen in metastatic disease, whereas melanomas are usually melanotic and are not associated with pain. Metastatic tumors exhibit medium to high reflectivity pattern on ultrasound A scan, whereas melanomas usually display a low to medium pattern. A patchy, diffuse interocular mass with episcleral and/or orbital involvement is consistent with metastatic tumor of the eye, whereas melanomas tend to be more localized.

Adult↗

PubMed1990

I-131 accumulation in gastric pull-up simulating pulmonary metastases on total-body scan for thyroid cancer.

A follow-up total-body I-131 scan in a patient with follicular thyroid carcinoma demonstrated radionuclide accumulation in the right hemithorax. Originally thought to be pulmonary metastatic thyroid carcinoma, the uptake region proved to be intrathoracic gastric mucosa. The patient had been treated for squamous cell esophageal carcinoma by esophagogastrostomy reconstruction with gastric pull-up. This unusual imaging pattern could have been interpreted as metastatic disease in the absence of complete patient records, an appreciation of normal gastric concentration patterns of I-131, and corroborative imaging study analysis.

Carcinoma, Squamous Cell↗

PubMed1993

Early detection of relapse after treatment for metastatic germ cell tumour of the testis: an exercise in medical audit.

The relapse patterns of 29 patients who recurred following treatment for metastatic germ cell tumours of the testis (seminoma n = 7, non-seminomatous germ cell tumour n = 22) have been analysed and the relative effectiveness of clinical follow-up and routine investigations in detecting relapse at an early stage have been examined. The analysis shows that routine estimation of the serum tumour markers human chorionic gonadotrophin and alpha-foetoprotein (HCG and AFP) is the single most important follow-up procedure. This is so, even in patients who were previously marker negative; it was the first indicator of relapse in 55% of the patients. Regular clinical examination and chest radiograph in asymptomatic patients was of little value. Chest radiograph gave the first evidence of relapse in only 2 cases (7%). The optimum frequency for follow-up computed tomographic scanning of the chest and abdomen remains debatable. In this series, it was the first abnormal investigation in 7 patients (24%) and proved to be particularly important in patients who had residual radiological abnormalities at the end of initial therapy. Cost analysis shows that intensive follow-up produces a total expenditure on investigations of approximately 4,500 pounds per relapse detected. Regular computed tomographic scanning is especially demanding on resources and costs approximately 12,880 pounds per relapse detected if the recommended protocol is followed.

Adult↗

PubMed1993

Cytogenetic abnormalities and clinical stage in testicular nonseminomatous germ cell tumors.

To study the impact of chromosomal abnormalities on the clinical behavior of testicular nonseminomatous germ cell tumors (TNSGCTs), we compared the chromosomal constitution of primary tumors of patients who initially presented and remained without metastases to those with metastatic disease. Furthermore, the chromosomal pattern of primary TNSGCTs was compared to ploidy and the clinicopathologic risk factors histology and small-vessel invasion. The modal chromosome number and the ploidy were in agreement. No correlation was found between the modal chromosome number and histology, presence of vascular invasion, or clinical stage. No correlation was found between structural chromosome abnormalities, like the number of copies of the i(12p) chromosome, and clinical stage. No obvious differences were found in chromosomal constitution of metastatic and non-metastatic tumors. The results of the present study suggest that in TNSGCTs differences in clinical behavior are not associated with gross chromosomal differences.

Adult↗

PubMed2002

Mapping of the keratin polypeptides in meningiomas of different types: an immunohistochemical analysis of 463 cases.

Keratins are known to be expressed in some meningiomas, and they have been consistently reported in secretory meningiomas. However, the expression of individual keratin polypeptides has not yet been systematically explored, and such a study could provide important information for the differential diagnosis of meningioma and other tumors, particularly metastatic carcinomas. In this study we analyzed the keratin polypeptide patterns of 463 meningiomas of different types using well-characterized monoclonal antibodies specific to 11 individual keratins and 3 additional antibodies that recognize more than 1 keratin. Archnoid tissues from autopsies were examined for comparison. Secretory meningiomas showed consistent positivity for all simple epithelial keratins K7, K8, K18, and K19, usually limited to the slender spindle cells lining the gland-like lumina. Other keratins variably detected in a minority of gland-like structures were K5/6, K14, K16, and K17. Among other meningiomas, keratin 18 was commonly present in a significant number of tumor cells in different subtypes (30% to 80% of cases), often extensively. The K18 positivity of meningiomas paralleled that observed in normal arachnoids, which were negative for K7, K8, K19, and AE1. Only rare meningiomas, other than the secretory ones, had significant positivity for K7, K8, K19, and other keratins than K18. The concentric spindle cells around psammoma bodies and few other spindle cell foci were often focally positive for K7 and to lesser degree for K8, K14, and K19. The complex pattern of keratins in meningiomas has to be considered in the differential diagnosis of meningioma and metastatic carcinoma. In this context, antibodies to K7, K8, and K19 and the antibodies AE1 and AE3 are useful, because they only rarely label significant numbers of meningioma cells but are positive in a great majority of carcinomas. Careful histologic analysis is necessary to differentiate anaplastic meningiomas and metastatic carcinomas, which have overlapping patterns of several keratins except K20, which was never present in any type of meningioma.

Adolescent↗

PubMedDate not supplied

Use of CT in metastatic adrenal gland tumor.

The autopsy findings and CT scans on patients with adrenal metastatic tumor over a six year period were analyzed. No pattern on CT was felt to be specific for metastatic tumor to the adrenal glands. Bilateral adrenal metastatic disease was found more common than unilateral disease by CT and by autopsy. All patients with adrenal metastatic disease had metastatic disease elsewhere. CT showed the other metastatic disease in approximately 90% of the cases. All our patients with follow-up scans showed change in the size of the tumor. CT remains the modality of choice for evaluation of the adrenal glands.

Adrenal Gland Neoplasms↗

PubMedDate not supplied

Wheat germ agglutinin binding to cells derived from in vivo grown solid tumors.

Binding of Wheat Germ Agglutinin (WGA) to cell suspensions derived from in vivo grown solid rat tumors of independent origin and of different metastatic potential has been examined, and results compared with previous work in other systems. The assay used to assess binding was based on the reaction of iodine 125-labelled lectin to tumor cells in suspension and values expressed as per cent of values of a cell line used as internal standard. Inhibition studies showed that WGA binding was principally to sialic acid and/or N-acetyl glucosamine residues. Binding parameters Bmax (maximal binding) and Kd (affinity of binding), derived from Woolf plots and expressed as per cent of internal standard cell line, were found for rat tumors Mc7, Mc40A, Sp24 and Walker 256. It was observed that cell suspensions derived from the metastatic and most tumorigenic tumor, Walker 256, exhibited a different pattern of lectin binding to the other non-metastatic and less tumorigenic tumors; in particular, Kd values were lower. These results are in accord with work using cell lines selected in vitro and are further evidence for a correlation between the density and/or configuration of cell surface sialic acid residues and metastatic potential.

Animals↗

PubMed1999

Role of radiotherapy in sarcoma of the breast--a retrospective review of the M.D. Anderson experience.

BACKGROUND: The role of adjuvant radiotherapy for sarcoma of the breast, based on local extension of disease and patterns of failure, remains undefined because of the rarity of the disease presentation. METHODS: Fifty-nine cases of soft tissue sarcoma of the breast were retrospectively reviewed. Cystosarcoma phylloides was excluded from analysis. Surgical intervention consisted of segmental resection (n = 16) or mastectomy (n = 38); five patients underwent excisional biopsy. Adjuvant radiotherapy was administered in four patients following segmental resection and in 13 patients after mastectomy. Doses totaled 50 Gy in the majority of patients, and conventional criteria and radiotherapy techniques for adjuvant breast irradiation were used. RESULTS: None of the dissected axillary nodes contained metastatic tumor on pathologic review. Patterns of failure were evaluated. Tumor size (P < 0.03) and surgical margins (P < 0.002) were predictive of local failure (LF). Due to limited patient numbers, no statistical significance was identified with any treatment modality. Following mastectomy alone, LF occurred in 13 patients (34%) versus the 13% rate of LF with mastectomy and radiotherapy (P = NS). Distant metastases developed concurrently with the two local failures in the group that underwent mastectomy and radiation. After segmental mastectomy, LF occurred in 3 cases (25%) concurrent with distant metastases: no LF were noted after segmental mastectomy and radiation (P = 0.27). For all treatment groups, local recurrences were characterized as multiple and involved the chest wall. Local failure occurred in 60% of patients with positive surgical margins who did not receive adjuvant irradiation. Irrespective of surgical margins, over 75% of local recurrences developed among patients treated by surgery alone. CONCLUSIONS: The role of radiotherapy for breast sarcoma remains undefined due to the rarity of this disease presentation. This retrospective review failed to demonstrate a statistical benefit for the administration of adjuvant irradiation in sarcoma of the breast, probably because of limited patient numbers. Because large tumor size and positive surgical margins incur a higher risk for LF, radiotherapy is probably indicated in these cases. Axillary dissection obligates the radiotherapist to treat the axilla in order to include all tissues in the surgical bed, and should be avoided to reduce potential treatment related morbidity. Established therapeutic principles and techniques used for both soft tissue sarcoma and breast cancer should continue to be applied.

Adolescent↗