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PubMed2003

The pattern of prostate-specific antigen responses following hormonal therapy in Thai men with bone metastatic prostate cancer.

OBJECTIVE: To study the pattern of prostate-specific antigen (PSA) responses and prognostic factors following hormonal therapy in Thai men with bone metastatic prostate cancer. MATERIAL AND METHOD: Forty-four patients with bone metastatic prostate cancer treated by bilateral orchiectomy were retrospectively studied for PSA responses during follow-up. The endpoint was time to PSA biochemical failure. PSA pattern and the prognostic factors were evaluated. RESULTS: PSA levels regressed to PSA nadir level in all patients. Time to 50 per cent PSA regression, time to PSA nadir level and time to biochemical failure were 2.1, 6.7 and 11.2 months, respectively. While biochemical failure was present, all patients were alive and had stable clinical conditions. Tumor grading was an important prognostic factor while age and pretreatment PSA level were not a significant indicator. Times to biochemical failure in the patients with well, moderate and poor differentiated tumors were 19.3, 10.0 and 9.3 months, respectively. CONCLUSION: Following bilateral orchiectomy in Thai men with bone metastatic prostate cancer, PSA level decreased continuously to the PSA nadir level in 6-7 months and stable for a period then it increased, known as biochemical failure. The patients with a well differentiated tumor had a significantly longer time to biochemical failure when compared to the patients with a moderate or poor differentiated tumor.

Aged↗

PubMed2004

Noninvasive in vivo detection of prognostic indicators for high-risk uveal melanoma: ultrasound parameter imaging.

PURPOSE: Primary malignant melanoma of the choroid and ciliary body has traditionally been treated without histologic staging, using purely clinical indicators. The presence of extravascular matrix patterns (EMP) in histologic sections of uveal melanoma has been shown to be an independent indicator of metastatic risk. These patterns are of a dimension and physical composition that are likely to be detected with ultrasound backscatter analysis. Our aim was to determine whether ultrasound parameter imaging could detect the presence of EMP at a diagnostically significant level for treatment staging and for planning investigational studies of therapeutic modalities. DESIGN: Prospective, masked ultrasound-pathologic correlative study. PARTICIPANTS: One hundred seventeen patients diagnosed with previously untreated choroidal melanoma were scanned within 2 weeks before enucleation. METHODS: Tumors were evaluated histologically and divided into high-risk and low-risk groups on the basis of the presence of 2% or more histologic cross-sectional area composed of EMP patterns. Digital ultrasound data were processed to generate parameter images representing the size and concentration of ultrasound scatterers. Histologic and ultrasound images and data were correlated, and linear and nonlinear statistical methods were used to create multivariate models for noninvasive differentiation of high-risk and low-risk tumors. MAIN OUTCOME MEASURES: Presence or absence of high-risk EMP and associated ultrasound parameter classification models. RESULTS: Of the 117 tumors, 69 were classified as low risk, and 48 were classified as high-risk with histologic analysis. A classification that used ultrasound parameter image features with linear discriminant analysis could correctly identify 79.5% of cases retrospectively and 75.2% of cases by use of cross-validation, an estimate of prospective classification ability. By use of a more powerful classification technique (support vector machine), 93.1% of cases were correctly classified retrospectively. With a cross-validation procedure, 80.10% of cases were correctly classified. CONCLUSIONS: Ultrasound can be used noninvasively to classify tumors into high-risk and low-risk groups by detecting the presence of EMP patterns. By the use of previous studies that compared the histologic presence of EMP patterns with patient survival, estimates of hazard rates associated with ultrasound risk groups can be made. The noninvasive ultrasound classification is potentially useful as a prognostic variable and as a tool for stratification of patient populations for tumor treatment evaluation.

Eye Enucleation↗

PubMed1980

Patterns of involvement of the temporal bone in metastatic and systemic malignancy.

The temporal bone appears to be involved with secondary malignant processes in discrete histologic patterns with rather characteristic clinical presentations. Five distinct types of involvement can be recognized: isolated metastasis from a distant primary tumor; direct extension from a regional primary tumor; meningeal carcinomatosis; leptomeningeal extension from an intracranial primary tumor; and leukemic or lymphomatous infiltration. The typical histopathological patterns are described with correlative clinical symtomatology. Differential diagnosis is considered, and guidelines for surgical management are discussed.

Brain Neoplasms↗

PubMed1992

Relationship of tumor cell motility and morphologic patterns. Part 1. Melanocytic skin tumors.

In the diagnosis of melanocytic skin tumors, the assessment of the overall architectural pattern (silhouette) is often essential. We have previously shown by a computer simulation model that tumor patterns are likely to depend on the relative degrees of proliferation and motility of the tumor cells. In this study, we examined the morphological pattern of 12 cases each of nevocellular nevi, primary melanoma, and metastatic melanoma by image analysis. The patterns of the individual melanocytic skin tumors were compared statistically with patterns generated by computer simulation, which facilitates estimates of biological properties of the tumor cells. Additionally, mitotic counts were made to measure tumor cell proliferation. A comparison of the three diagnostic groups revealed that the cells of nevocellular nevi show a low degree of motility, which, however, still exceeds the very low degree of proliferation. Thus, an "invasive" pattern with numerous small nests and single cells at the base of the lesion is common. In primary malignant melanoma, tumor cell motility and tumor cell proliferation are significantly increased in various proportions, thus leading to varying morphological patterns. In metastatic melanoma, a strikingly elevated degree of proliferation exceeds the only slightly elevated degree of motility and leads to sharply demarcated, "expansive" lesions. To check the validity of the technical procedure, estimates of proliferation based on pattern analysis alone were compared with the results obtained by mitotic counts. There was a significant correlation, indicating that the assumptions of the computer model and the image analysis procedure are in fact applicable to real-life melanocytic skin tumors.(ABSTRACT TRUNCATED AT 250 WORDS)

Cell Division↗

PubMed2004

Integrin chains beta1 and alphav as prognostic factors in human metastatic melanoma.

The expression pattern of integrin-type cell adhesion receptors is often changed during malignant transformation. In the present work, we studied the prognostic significance of beta1 and alphav integrin chains for survival of patients with metastatic melanoma. The expression levels of beta1 integrin were also compared with those of Bcl-2, an anti-apoptotic protein, the presence of which is associated with treatment response and survival in melanoma. The expression of beta1 and alphav integrins in 68 melanoma metastases obtained from 55 patients treated with combined chemoimmunotherapy was studied by immunohistochemistry using anti-beta1 and anti-alphav antibodies. The patients were divided into two groups (using a cut-off point of >/= 81%) for beta1 integrin expression levels and into three categories (negative/low, median, high) for alphav integrin expression levels. All tumours were positive for beta1 integrin, and the tumours (n = 6) which had the highest alphav score were also strongly positive for beta1 (94%; P = 0.0055). Patients (n = 43) with 80% or less beta1 integrin-positive tumour cells in their samples had a median disease-free survival (DFS) of 17.0 months, and patients (n = 12) with 81% or more beta1 integrin-positive tumour cells had a DFS of only 5.7 months (P = 0.0001). Patients (n = 32) with low alphav integrin expression levels had shorter DFS (median 12.3 months; P = 0.0146) than patients (n = 20) with median expression levels (median 16.7 months; P = 0.0146). However, three patients who had a very strong alphav expression in their tumours had a median DFS of only 1.8 months (P = 0.0146). Median level expression of beta1 integrin was associated with the presence of Bcl-2 in tumour cells (P = 0.0033). Our results suggest that beta1 and alphav integrin chains are independently expressed in metastatic melanoma and may have an effect on the metastatic potential of melanoma cells.

Adult↗

PubMed1993

Surgical experience with 5 n3(+) early gastric carcinoma cases.

Of 370 patients who underwent a resection for early gastric carcinoma, 317 (85.6%) were N(-), 28 n1(+), 20 n2(+) and five (1.4%) n3 respectively. In this study, n3(+) early gastric cancers were clinicopathologically evaluated and sites of the metastatic nodes were also defined. In addition, a comparative study in DNA ploidy patterns between primary and metastatic node cell was performed according to Hedley's method using a FACS-IV scan of paraffin-embedded tissues. All n3(+) early gastric cancers showed an aneuploidy pattern. R2 or R3 operations are recommended for early gastric carcinomas with aneuploidy pattern and most of the metastatic nodes arise from the identical stem cell line of cancer cells.

Aged↗

PubMed1991

Invasion and metastasis: biology and clinical potential.

Metastatic dissemination of tumor is the primary cause of death for most cancer patients. The expanding field of study of the metastatic cascade has been the source of novel approaches to the diagnosis and treatment of cancer. The metastatic process involves angiogenesis, tumor cell adhesion to vascular basement membrane, local proteolysis to create an opening in the basement membrane, migration through that rent and into the secondary site, and finally, successful proliferation. Important components of the metastatic cascade such as basement membrane structures, adhesion molecules and their receptors, proteolytic enzymes, migration-inducing factors, and growth factors have been demonstrated to have reproducible patterns in malignant and metastatic tissues. These patterns have led to clinical correlations demonstrating their utility in the identification and follow-up of malignant and metastatic disease. In addition, several promising new anti-cancer drugs such as inhibitors of angiogenesis, protease-inhibitors, and blockers of signal transduction have been identified and are awaiting introduction into the clinical arena.

Animals↗

PubMed1997

Analysis of giant cell tumor of bone with pulmonary metastases.

The authors reviewed 6 cases of giant cell tumor of bone with pulmonary metastases, analyzed the growth rate of the metastases, and performed flow cytometry on paraffin blocks from primary and metastatic lesions. Surgery on the pulmonary metastases was done in 3 cases. Chemotherapy was administered in all 6 cases. If the doubling time of the pulmonary metastases was more than 80 days, the case was considered to be slow growing or in regression. However, if the doubling time was approximately 30 days, the prognosis was poor. The cases were divided into 3 types according to the prognosis. After chemotherapy (cyclophosphamide), the pulmonary metastases decreased in size in 2 cases. In 2 other cases, the metastases were slow growing, and the remaining 2 patients died early. Flow cytometric analysis was performed on primary and metastatic lesions, which showed a diploid pattern in most cases, but a tetraploid pattern in 1 recurrent case. Pulmonary metastatic lesions displayed a diploid pattern in 4 cases from which materials were taken either at surgery or autopsy.

Adolescent↗

PubMed1997

Tumor growth and metastasis of human colorectal cancer cell lines in SCID mice resemble clinical metastatic behaviors.

Ten human colorectal cancer (CRC) cell lines were implanted orthotopically into the ceca and also into the livers, muscles and peritoneal cavities of SCID mice in order to analyze the characteristics regulating metastatic behaviors of CRCs. All the CRC cell lines formed tumors in the muscle and cecum, but they could be classified into two groups: (1) six cell lines with high tumorigenicity in the liver (HTLs) forming differentiated tumors, and (2) four with no tumorigenicity in the liver (NTLs) forming poorly differentiated tumors in SCID mice. After orthotopic implantation, NTLs never metastasized to the liver, whereas HTLs did. Therefore, intrahepatic tumorigenicity and differential status were closely associated with liver metastasis whereas differentiation was not associated with lung metastasis. The 6 HTLs demonstrated an inverse correlation between liver metastases and peritoneal dissemination, and immunohistochemistry indicated expression of sLeX, CA19-9 and carcinoembryonic antigen in tumors which correlated well with the liver metastatic rate. We found a strong correlation between liver metastasis and intrahepatic tumorigenicity and could reproduce the clinical correlations between the pattern of the metastatic spread and the differentiation phenotype of CRC in vivo. We consider further examination using this model will be useful for analyzing the complex mechanisms involved in clinically metastasizing CRCs.

Adenocarcinoma↗

PubMed1996

A metastatic neuroblastoma model in SCID mice.

Neuroblastoma (NB), a neural crest derived tumor in children, shows a characteristic pattern of dissemination that includes adrenal glands, local lymph nodes, bone, liver, skin, and bone marrow. We have reconstructed a similar metastatic pattern in SCID mice following tail vein injection of human NB cells. HTLA230, an NB cell line isolated from a patient with advanced disease, and its NGF receptor (trkA) expressing derivative (18-10) cells, consistently disseminated to the liver, the adrenal gland, and the bone marrow, but not the lungs. Metastases in the different organs showed a characteristic hemorrhagic histopathology, and tumors in the bone marrow presented as syncytia-like cell aggregates, typically seen in patients. Cell lines reestablished from 18-10 derived liver and bone marrow metastases maintained their cellular morphology, growth behavior, N-myc overexpression, trkA expression, and functionally responded to NGF treatment, leading to growth arrest and neurite outgrowth. Hence circulating human NB cells in SCID mice show a similar organ-specific metastatic potential as seen in patients, independent of trkA expression.

Adrenal Gland Neoplasms↗

PubMed1993

[Clinical significance of flow cytometric DNA analysis in patients with rectal cancer].

DNA content was measured by flow cytometry using paraffin-embedded material from 148 primary rectal cancers and 10 distant metastatic lesions. DNA ploidy pattern was classified into the following three groups in terms of the DNA index: 1.00 was defined as the diploid group (DP), 1.00 < DNA index < 1.60 as the low-aneuploid group (LAP) and > or = 1.60 as the high-aneuploid group (HAP). Primary carcinomas were DP in 26.4%, LAP in 36.5% and HAP in 37.1%. The DNA ploidy pattern of the primary tumor correlated well with clinicopathological findings such as depth of invasion, lymphatic invasion, pathological stage, metastasis to distant organs and curability of the tumor. In patients with HAP tumor after curative operation, the recurrence rate (21.6%) in distant organs was significantly higher than those with DP tumor (2.8%) and LAP tumor (6.4%) [p < 0.05]. Two LAP patients and 8 HAP patients with distant metastatic disease had the same DNA ploidy pattern HAP in the metastatic lesions. These data indicate that tumor DNA ploidy patterns classified into three groups in rectal cancer may play an important role in predicting prognosis, including distant metastasis.

DNA, Neoplasm↗

PubMed2006

Fibronectin is distinctly downregulated in murine mammary adenocarcinoma cells with high metastatic potential.

In the present work we used a murine mammary cancer model of two related adenocarcinomas with different lung metastasizing abilities, to compare their global gene expression profiles. Clontech Atlas mouse cDNA microarrays of primary cultured tumor cells were employed to identify genes that are modulated in the more metastatic variant MM3 relative to its parental tumor M3. A total of 88 from 1,176 genes were differentially expressed in MM3 primary cultures, most of them (n=86) were upregulated. Genes were grouped according to their functions as associated with signal transduction and transcription regulation (e.g. Stat1 and Zfp 92), with cell adhesion and motility (cadherin 1, fibronectin), with invasion and angiogenesis (uPA, 72 kDa MMP2), with the regulation of cell proliferation and cell death (cyclins G and A2, TNF), and also included growth factors and receptors, oncogenes and tumor suppressors genes (p107, TGFbeta2, TBR-I, PDGFR). Only 2 genes, TTF1 and fibronectin (FN), showed a significant downregulation. Notably FN expression, loss of which has been associated with a malignant phenotype, was reduced about 19-fold in the more metastatic MM3 cells. Previously known differences in expression patterns associated with the metastatic capacity of MM3 and M3 adenocarcinomas, including downregulation of FN or upregulated expression of TGFbeta and proteases, were confirmed by the array data. The fact that FN was one of the only two genes significantly down-regulated out of the 1,176 genes analyzed stresses the hypothesis that FN may behave as an important metastasis suppressor gene in mammary cancer.

Adenocarcinoma↗

PubMed2005

Biomechanical assessment of stability in the metastatic spine following percutaneous vertebroplasty: effects of cement distribution patterns and volume.

Percutaneous vertebroplasty is a minimally invasive, radiologically guided procedure whereby bone cement is injected into structurally weakened vertebrae to provide added biomechanical stability. In addition to treating osteoporotic vertebral fractures, this technique is also used to relieve pain by stabilizing metastatically compromised vertebrae that are at risk of pathologic burst fracture. Optimal cement distribution patterns to improve biomechanical stability to metastatically involved vertebral bodies remain unknown. This study aimed to determine the effect of cement location and volume of cement injected during percutaneous vertebroplasty on improving vertebral stability in a metastatically-compromised spinal motion segment using a parametric poroelastic finite element model. A three-dimensional parametric finite element model of a thoracic spinal motion segment was developed and analyzed using commercially available software. A total of 16 metastatic pre and post vertebroplasty scenarios were investigated using a serrated spherical representation of tumor tissue and various geometric representations of polymethylmethacrylate (PMMA). The effect of vertebroplasty on vertebral bulge, a measure of posterior vertebral body wall motion as an indicator of burst fracture initiation, was assessed. In all cases, vertebroplasty reduced vertebral bulge, but the risk of the initiation of burst fracture was minimized with cement located posterior to the tumor, near the posterior vertebral body wall. Vertebral bulge decreased by up to 62% with 20% cement injection. These findings demonstrate that location and distribution of cement within the vertebral body has a noticeable effect on the restoration of biomechanical stability following percutaneous vertebroplasty.

Bone Cements↗

PubMed1984

Ovarian androblastoma metastatic to tonsil.

Structural pattern of a tonsillar tumor found in a 67-year-old female was similar to a small ovarian androblastoma diagnosed histologically 6 1/2 years earlier. Electron microscopic study of the tonsillar mass revealed crystalloid structures suggestive of the Leydig cell origin of the tumor. After tonsillectomy, there was no local recurrence of the tumor, but the patient died a year later of multiple metastases. There appeared to be no previous reports of ovarian tumors metastatic to tonsil, and malignant androblastomas of the Leydig cell type are extremely rare.

Female↗

PubMed1991

Metastasizing eccrine porocarcinoma. Report of two cases with fatal outcome.

The clinical, histopathological and ultrastructural features of a metastasizing eccrine porocarcinoma are described in a 75-year-old woman and a 82-year-old woman. The previously not recognized tumors were identified by its distinct pattern of metastasis. Metastatic spreading was restricted for years to a circumscribed region of the skin. Histology and electron microscopy disclosed pronounced epidermotropism of the PAS-positive tumor cells. The characteristic pattern of dissemination obviously represents a homing phenomenon of the tumor cells derived from the intraepidermal sweat gland duct.

Adenoma, Sweat Gland↗

PubMed1998

Hevin, an antiadhesive extracellular matrix protein, is down-regulated in metastatic prostate adenocarcinoma.

Hevin, a gene closely related to the extracellular matrix protein SPARC, is an acidic cysteine-rich glycoprotein shown to be important for the adhesion and trafficking of cells through the endothelium. Through the use of differential display and differential EST analysis, we identified Hevin as a gene whose transcription is down-regulated in transformed prostate epithelial cell lines and metastatic prostate adenocarcinoma. These results were confirmed by comparing expression levels between normal and neoplastic human prostate tissues using Northern analysis. In situ hybridization with an 35S-labeled antisense riboprobe demonstrated the loss of Hevin expression in metastatic prostate carcinoma. The expression pattern of Hevin in transformed and metastatic epithelium may provide further insights into the complex cell adhesion events involved in the metastatic progression of prostate carcinoma.

Adenocarcinoma↗

PubMed1986

Histiocytic appearance of metastatic lobular breast carcinoma.

Autopsy findings in a case of widely disseminated lobular breast carcinoma showed an unusual histiocytoid appearance in metastases to the uterus and parathyroid gland. This morphology for breast carcinoma has been previously reported in eyelid metastases. Recognition of this pattern in other metastatic sites has important diagnostic and therapeutic implications. Problems might have arisen if the polypoid uterine mass had been the presenting lesion during life. We also review the occurrence of metastatic breast carcinoma in the uterus and parathyroid gland.

Adult↗

PubMed2000

Cytokeratin profile relates to histological subtypes and intrahepatic location of intrahepatic cholangiocarcinoma and primary sites of metastatic adenocarcinoma of liver.

AIMS: We evaluated the cytokeratin profile of intrahepatic cholangiocarcinoma with respect to its histological classification and intrahepatic location (peripheral vs. hilar), and compared its profile with that of a variety of metastatic adenocarcinomas in liver. METHODS AND RESULTS: Expression of cytokeratins 7, 8, 18, 19 and 20 was immunohistochemically examined in intrahepatic cholangiocarcinoma (n = 77) and metastatic adenocarcinoma in liver (21 colorectal, 14 gastric, three gallbladder and three pancreatic cancers). Materials were autopsy or surgical specimens. Cytokeratins 7, 8, 18 and 19 were expressed in 75 (97%), 75 (97%), 59 (77%) and 71 (92%) cases of intrahepatic cholangiocarcinoma, respectively. Moderate and extensive expression of cytokeratin 18 was more frequent in the peripheral than in the hilar type. Moderate and extensive expression of cytokeratin 19 was seen in almost all cases of well-differentiated intrahepatic cholangiocarcinomas, while expression was decreased relatively in the moderately and decreased more in the poorly differentiated cases. While cytokeratin 20 was not found in non-neoplastic biliary epithelia or in well-differentiated intrahepatic cholangiocarcinomas, this cytokeratin was occasionally detectable in moderately and poorly differentiated intrahepatic cholangiocarcinomas and its expression was more frequent in the hilar type. Cytokeratin 20 expression was observed in 17 (81%) of metastatic adenocarcinomas in liver from colorectal regions, to a lesser degree in those from gastric regions, and was rare in those from gallbladder and pancreatic regions; cytokeratin 7 showed a reverse expression pattern in these metastatic adenocarcinomas in liver. The profile of cytokeratins 7 and 20 of metastatic colorectal and gastric carcinomas differed from that for intrahepatic cholangiocarcinomas, while that of metastatic gallbladder and pancreatic carcinoma was similar to that for intrahepatic cholangiocarcinomas. Moreover, cytokeratin 18 and 19 expression was significantly infrequent in metastatic gastric carcinomas than in intrahepatic cholangiocarcinomas and metastatic colorectal carcinomas. CONCLUSION: The combined immunostaining of cytokeratins 7, 18, 19 and 20 is useful for the characterization of intrahepatic cholangiocarcinomas with respect to histological subtypes and intrahepatic location. It helps to differentiate intrahepatic cholangiocarcinoma from metastatic adenocarcinomas in liver and from colorectal and gastric regions; it also indicates the primary focus metastatic adenocarcinomas in livers.

Adenocarcinoma↗