[Patterns of serum lactic dehydrogenase (EC,1.1.1.27) isoenzymes in the diagnosis of primary and metastatic neoplasms of the liver].
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Adolescent↗
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Results for “Metastatic patterns”
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The vascular architecture of renal cell carcinoma in fine-needle aspiration biopsies. An aid in its distinction from hepatocellular carcinoma.
BACKGROUND: The morphologic similarities between renal cell carcinoma (RCC) and hepatocellular carcinoma (HCC) can cause diagnostic difficulty in fine-needle aspiration biopsy (FNAB) specimens. In the authors' prior study of liver FNAB, peripherally wrapping endothelium (PE) and arborizing transgressing endothelium (TE) were 100% specific for HCC relative to metastatic tumors, which included only three RCCs. In this study, the vascular patterns of RCC in FNAB were reviewed for comparison with HCC, to determine their usefulness in the differential diagnosis of HCC and RCC. METHODS: FNAB of 49 RCCs (26 primary and 23 metastatic) from 46 patients were reviewed. Four vascular patterns were assessed: PE, TE, papillary endothelium (PAP) in fibrovascular cores of papillary fragments, and short nonbranching endothelium (SE) in small cell clusters. Each pattern was given a semiquantitative score: absent (0), focal (1), or extensive (2). Cellularity was categorized as low (< 20 groups), moderate (20-50 groups), or high (> 50 groups). RESULTS: Vessels were present in 19 of 26 (73%) primary and 9 of 23 (39%) secondary RCC. PE was not identified. TE was observed in 11 primary (42%) and 7 metastatic (30%) RCC. SE was present in 5 primary (19%) and 1 metastatic (4%) RCC. The TE and SE patterns were distributed among the clear cell, granular cell, and chromophobe RCC. PAP was observed in all four papillary RCC. The majority of the TE and all of the PAP were present in moderately to highly cellular FNABs, whereas SE was usually observed in FNABs with low cellularity. CONCLUSIONS: FNAB specimens of RCC commonly contain TE, as in HCC, but lack PE. TE was less frequent in metastatic than primary RCC. Other vascular patterns (SE, PAP), absent in HCC, were observed infrequently. Vascular patterns, especially PE, are useful in distinguishing HCC from RCC.
Biopsy, Needle↗
Influence of implantation site on growth, antigen expression and metastatic potential of human colonic cancer HT29 and 5583 xenografts in nude mice.
In order to study the interaction between tumors and host environmental factors, we xenografted cells from the human colonic carcinoma cell lines HT29 and 5583-S in the subcutis, cecum, spleen and liver of nude mice and compared growth characteristics, metastatic potential and some phenotypic features of the xenografts in these sites. No remarkable differences were observed between the tumors at different inoculation sites in regard of their expression of carcinoembryonic antigen and secretory component or type of mucin produced. Also the proportion of DNA synthesizing cells as determined by bromodeoxyuridine incorporation appeared to be comparable in the studied implantation sites. Local invasive growth characteristics and metastatic potential, however, showed marked differences. Subcutaneous and cecal xenografts frequently showed tumor cell invasion into the surrounding tissue, vasoinvasive growth and discontinuous basement membrane deposition, whereas splenic and hepatic implants demonstrated more encapsulation, no invasion of blood vessels and more continuous basement membrane deposition. Subcutaneous xenografts produced no metastasis. With HT29 cells liver and lymph node metastases occurred frequently from the splenic as well as the cecal xenografts. 5583 cells regularly produced liver metastases from the splenic xenografts, whereas no metastasis from cecal xenografts were observed. We conclude that although the patterns of invasive growth and the metastatic potential differ for various implantation sites, antigen expression and cell kinetic features of tumor implants are hardly influenced by the site of inoculation.
Animals↗
Differential diagnostic considerations and potential pitfalls in fine-needle aspiration biopsies of the mediastinum.
The mediastinum is the host for a number of relatively unusual primary neoplasms, as well as a frequent recipient of metastatic tumors. From the perspective of fine-needle aspiration cytomorphology, several distinct patterns are yielded. The polygonal (or epithelial-like) cell pattern may be seen with benign and malignant thymomas, germinomas, embryonal carcinoma, and many metastatic carcinomas. An intimate admixture of small lymphocytes with these epithelial cells may occur in this category. The small cell pattern may be produced by malignant non-Hodgkin's lymphomas, neuroblastoma, carcinoid tumors, and metastatic oat cell carcinoma. Uncommon morphologic forms of thymoma and carcinoid tumors, as well as benign mesenchymal lesions, may yield a picture of a spindle-cell proliferation. In addition to cytomorphology, the cytologist needs to integrate clinical, radiographic, immunocytochemical, and ultrastructural data to formulate a final diagnosis.
Biopsy, Needle↗
Tissue-Level Transcriptomic Entropy Reveals Organ-Specific Aging Patterns and Predicts Cancer Progression.
Although aging and cancer share complex molecular mechanisms, distinguishing causative factors from byproducts remains challenging. Here, we investigated the role of tissue transcriptomic entropy-a measure of transcriptional disorder-in aging and cancer processes by analyzing RNA-sequencing data from over 25,000 samples from human and mouse tissues. We found that entropy changes during aging are highly tissue-specific, with some tissues showing increased entropy while others exhibit decreased or stable entropy levels. Moreover, transcriptomic entropy strongly correlates with age-related processes, showing positive associations with proliferation, cellular senescence, somatic mutation burden, and cellular reprogramming, whereas it negatively correlates with stemness. In cancer, we observed that primary tumors generally display higher entropy than normal tissue, with its levels further increasing in metastatic stages. Cancer treatment modulated entropy patterns in multiple contexts, with changes suggesting a role for transcriptional complexity in tumor plasticity and therapy resistance. Elevated entropy levels predicted poor survival outcomes in multiple cancer types, suggesting its potential as a prognostic marker. Furthermore, differential expression analysis revealed that entropy-associated genes are enriched in developmental processes and depleted in metabolic pathways, indicating a possible link to cellular dedifferentiation. Finally, we found increased entropy in various age-related disorders beyond cancer, suggesting that transcriptomic entropy may be a common feature in age-related diseases. Our findings establish transcriptomic entropy as a fundamental parameter in aging and cancer progression, offering new insights into disease mechanisms.
Humans↗
Comparison of dynamic helical CT and dynamic MR imaging in the evaluation of pelvic lymph nodes in cervical carcinoma.
OBJECTIVE: This study compares dynamic helical CT with dynamic MR imaging in the evaluation of pelvic lymph nodes in cervical carcinoma. SUBJECTS AND METHODS: Women with biopsy-proven cervical carcinoma prospectively underwent dynamic helical CT and MR imaging before surgery. A metastatic node on CT and MR imaging was defined as a rounded soft-tissue structure greater than 10 mm in maximal axial diameter or a node with central necrosis. Imaging results were compared with pathology, and receiver operating characteristic curves for size and shape were plotted on a hemipelvis basis. Nodal density and signal intensity on CT and MR images, respectively, were reviewed for differences between benign and malignant disease. RESULTS: A total of 949 lymph nodes were found at pathology in 76 hemipelves in 43 women, of which 69 lymph nodes (7%) in 17 hemipelves (22%) were metastatic. Sensitivity, specificity, positive and negative predictive values, and accuracy of helical CT and MR imaging in the diagnosis of lymph node metastasis on a hemipelvis basis was 64.7%, 96.6%, 84.6%, 90.5%, and 89.5% and 70.6%, 89.8%, 66. 7%, 91.4%, and 85.5%, respectively. Receiver operating characteristic curves for helical CT and MR imaging gave cutoff values of 9 and 12 mm in maximal axial diameter, respectively, in the prediction of metastasis. Central necrosis had a positive predictive value of 100% in the diagnosis of metastasis. Signal intensity on MR imaging and density-enhancement pattern on CT in patients with metastatic nodes did not differ from those in patients with negative nodes. CONCLUSION: Helical CT and MR imaging show similar accuracy in the evaluation of pelvic lymph nodes in patients with cervical carcinoma. Central necrosis is useful in the diagnosis of metastasis in pelvic lymph nodes in cervical cancer.
Adult↗
Genomic analysis of metastasis reveals an essential role for RhoC.
The most damaging change during cancer progression is the switch from a locally growing tumour to a metastatic killer. This switch is believed to involve numerous alterations that allow tumour cells to complete the complex series of events needed for metastasis. Relatively few genes have been implicated in these events. Here we use an in vivo selection scheme to select highly metastatic melanoma cells. By analysing these cells on DNA arrays, we define a pattern of gene expression that correlates with progression to a metastatic phenotype. In particular, we show enhanced expression of several genes involved in extracellular matrix assembly and of a second set of genes that regulate, either directly or indirectly, the actin-based cytoskeleton. One of these, the small GTPase RhoC, enhances metastasis when overexpressed, whereas a dominant-negative Rho inhibits metastasis. Analysis of the phenotype of cells expressing dominant-negative Rho or RhoC indicates that RhoC is important in tumour cell invasion. The genomic approach allows us to identify families of genes involved in a process, not just single genes, and can indicate which molecular and cellular events might be important in complex biological processes such as metastasis.
Animals↗
Re-expression of reduced VEGF activity in liver metastases of experimental pancreatic cancer.
PURPOSE: Vascular endothelial growth factor (VEGF) is thought to play a crucial role in the process of cancer growth and metastasis. In this study, the expression of VEGF in liver metastases of pancreatic cancer was investigated using an established hamster model. METHODS: Pancreatic cancer cells (PGHAM-1, 1 x 10(6)) derived from N-nitrosobis (2-oxopropyl) amine (BOP)-induced pancreatic tumors in Syrian golden hamsters were transplanted into the pancreas of female hamsters. All hamsters were sacrificed at 21 days after transplantation and used for the histopathological examination of pancreatic and metastatic lesions (primary transplantation model). The metastatic liver tumors were minced with scissors and 1 mm(3) tumors were retransplanted into the pancreas of a second hamster. All hamsters were sacrificed 21 days after retransplantation, and the pancreatic tumors were removed (back transplantation model). Immunohistochemical analyses using antibody against VEGF were performed for all pancreatic and liver tumors. Reverse transcription-polymerase chain reaction (RT-PCR) was performed to examine the expression of VEGF mRNA in the tumors. In addition, we investigated the proliferation of each tumor using Ag-NOR staining. RESULTS: In the primary transplantation models, VEGF expression in the pancreatic tumors was positive, but that in the liver metastases was only weakly positive or negative. On the other hand, VEGF expression in the pancreatic tumors that had developed from the retransplantation of the liver tumors (back transplantation model) was strongly positive. VEGF mRNA was expressed in the pancreatic tumors of both primary and back transplantation models. In the metastatic liver tumors of the primary transplantation model, VEGF mRNA was expressed in all cases, although the immunohistochemical staining pattern was weakly positive or negative. Similarly, in the metastatic liver tumor of the back transplantation model, VEGF mRNA was expressed in all cases, although the immunohistochemical staining pattern was weakly positive or negative. No significant differences in Ag-NOR scores were found between the models. CONCLUSION: Our results suggest that VEGF expression usually occurs in PGHAM-1 cells but that VEGF expression is reduced during the process of liver metastasis and revived by retransplantation. Thus, the interrelationship between cancer cells and the organ environment might play an important role in VEGF expression.
Animals↗
[Cell kinetics in two cases of meningioma with ultra-late pulmonary metastases].
In order to elucidate the influence of surgical intervention on cell kinetics, we investigated the DNA ploidy pattern and mitotic index in two patients with metastatic pulmonary meningioma more than 10 years after the first operation for primary brain lesions. The first patient, with hemangiopericytomatous meningioma, showed a diploid pattern in all resected specimens and intrathoracic metastases obtained at autopsy, and also showed a constant mitotic indices throughout the clinical course. The second patient, with meningothelial meningioma, also showed a diploid pattern and constant mitotic indices throughout the clinical course. There was no difference in the two parameters between this second patient and 5 non-metastatic control cases. In conclusion, there was no positive correlation between these two parameters and the acceleration of tumor growth detected at every surgical intervention.
Adult↗
Identification of genes associated with ovarian cancer metastasis using microarray expression analysis.
Although the transition from early- to advanced-stage ovarian cancer is a critical determinant of survival, little is known about the molecular underpinnings of ovarian metastasis. We hypothesize that microarray analysis of global gene expression patterns in primary ovarian cancer and metastatic omental implants can identify genes that underlie the metastatic process in epithelial ovarian cancer. We utilized Affymetrix U95Av2 microarrays to characterize the molecular alterations that underlie omental metastasis from 47 epithelial ovarian cancer samples collected from multiple sites in 20 patients undergoing primary surgical cytoreduction for advanced-stage (IIIC/IV) serous ovarian cancer. Fifty-six genes demonstrated differential expression between ovarian and omental samples (P < 0.01), and twenty of these 56 differentially expressed genes have previously been implicated in metastasis, cell motility, or cytoskeletal function. Ten of the 56 genes are involved in p53 gene pathways. A Bayesian statistical tree analysis was used to identify a 27-gene expression pattern that could accurately predict the site of tumor (ovary versus omentum). This predictive model was evaluated using an external data set. Nine of the 27 predictive genes have previously been shown to be involved in oncogenesis and/or metastasis, and 10/27 genes have been implicated in p53 pathways. Microarray findings were validated by real-time quantitative PCR. We conclude that gene expression patterns that distinguish omental metastasis from primary epithelial ovarian cancer can be identified and that many of the genes have functions that are biologically consistent with a role in oncogenesis, metastasis, and p53 gene networks.
Bayes Theorem↗
[Prostate cancer-related metastatic bone disease. Some new acquisitions about pathogenesis an therapeutic approaches].
Anatomic patterns of blood flow and specific dynamic interactions between prostate cancer cell and bone microenvironment influence the distribution of metastatic deposits. Bone components preferentially bind cancer cell and can facilitate tumor growth in bone; cancer cells, in turn, can release some factors that enhance osteoblastic activity. Recent studies, in animal models, have provided evidences of chemoattractant factors (bone homing factors) and of an enhanced adherence of prostate cancer cells to bone marrow endothelium. Additional data suggest "osteomimetic" pattern of prostate cancer cells after their arrival in bone, particularly by taking an osteoblastic behavior. The presence of the cancer cell in bone results in bone matrix increased turnover. Although prostate cancer is characterized by osteoblastic metastases, bone resorption is a regular feature of this tumor and is a necessary factor for its invasiveness in bone. Current treatment options based on radiotherapy and pharmacotherapy are essentially palliative. The bisphoshonates inhibit osteoclastic bone degradation by several mechanisms. Improved knowledges of the molecular mechanisms in the development of skeletal metastases allow to foresee biologically-based therapeutic strategies.
Bone Neoplasms↗
Poorly-differentiated adenoid cystic carcinoma: cytologic appearance in fine-needle aspirates of distant metastases.
Adenoid cystic carcinoma (ACC) is a primary salivary-gland neoplasm which typically yields characteristic cytomorphology upon fine-needle aspiration (FNA). We report on the FNA findings of a case of ACC metastatic to the liver which demonstrated a predominantly solid, poorly-differentiated pattern, an unusual but well-recognized subtype associated with a poor clinical outcome. The FNA findings in 7 additional cases of ACC metastatic to distant sites were also reviewed, with 4 cases displaying a prominent poorly-differentiated component. These findings suggest that, although not commonly recognized in salivary-gland FNAs, the poorly-differentiated pattern of ACC does occur in metastatic deposits and should be recognized as such, thereby preventing a needless search for a second primary malignancy.
Biopsy, Needle↗
Potential crosstalk between insulin-like growth factor receptor type 1 and epidermal growth factor receptor in progression and metastasis of pancreatic cancer.
The insulin-like growth factor receptor type 1 (IGF1R) and epidermal growth factor receptor (EGFR) are reportedly overexpressed in pancreatic cancer. However, the correlation between activated EGFR and IGF1R and their clinicopathological implications still remain unclear. The cellular localization and overexpression of IGF1R and EGFR were investigated immunohistochemically in primary invasive ductal pancreatic carcinomas obtained from 74 patients who underwent radical surgical resection. We also compared the status of IGF1R and EGFR overexpression between primary tumors and hepatic metastatic tumors obtained from 44 autopsied patients. Among the 74 surgically resected primary tumors, cytoplasm- and membrane-dominant EGFR overexpression was detected in 22 (30%) and 7 (9%), respectively, whereas cytoplasm- and membrane-dominant IGF1R overexpression was detected in 8 (11%) and 28 (38%), respectively. Membrane-dominant EGFR and cytoplasm-dominant IGF1R were more frequent in lower-grade tumors and correlated with favorable prognosis, whereas cytoplasm-dominant EGFR and membrane-dominant IGF1R were more frequent in higher-grade tumors and correlated with poor prognosis. In 36 autopsy specimens of pancreatic tumor with concurrent overexpression of IGF1R and EGFR, there was an inverse correlation between the IGF1R and EGFR localization patterns (P = 0.001). In the hepatic metastatic tumors obtained by autopsy, the incidences of both IGF1R and EGFR overexpression were much higher than in the surgically resected primary tumors. More than half of the autopsy cases consistently showed membrane-dominant EGFR expression in both the primary tumor and hepatic metastases, whereas IGF1R expression showed considerable variation. Crosstalk between differently localized IGF1R and EGFR might play a role in determining the biological aggressiveness of pancreatic cancer, although their cellular localization may often alter during the process of metastasis.
Adenocarcinoma↗
Flow cytometric DNA-ploidy and proliferative activity of diethylnitrosamine-induced hepatocellular carcinoma and pulmonary metastases in monkeys.
Flow cytometric DNA analysis was carried out on diethylnitrosamine (DEN) induced primary hepatocellular carcinomas (HCC) and lung metastases in monkeys. In analyzing one sample from each of 133 HCC cases, 76 (67.2%) were diploid and 37 (32.7%) aneuploid. When more samples were analyzed from the same tumorous liver, all of the 76 diploid cases maintained their pattern, whereas 5 (13.5%) of the aneuploid cases displayed both diploid and aneuploid DNA. Studies of lung metastases from 44 (28 diploid, 16 aneuploid) HCC cases showed that the DNA-ploidy pattern characterizing the primary HCC was preserved in the metastases in 78.6% of the diploid and 93.7% of the aneuploid cases. The average synthetic phase fraction (SPF) value for the diploid tumors was 7.7% and the aneuploid tumors 14.9%. The difference is highly significant (P < .01). Highly significant correlation was found between the DNA ploidy and the SPF values, both in the primary HCC (P = .0001) and the metastases (P = .0266). Of different tumor and host features examined, statistically significant correlation was only found between DNA-ploidy/SPF and the cytological tumor grade. This study represents the first DNA-ploidy analysis of HCC in monkeys. The data showed that diploid and aneuploid tumors displayed comparable metastatic potential. The DNA-ploidy pattern was preserved in the metastases in the majority of the cases.
Animals↗
Predicting survival in patients with metastatic kidney cancer by gene-expression profiling in the primary tumor.
To identify potential molecular determinants of tumor biology and possible clinical outcomes, global gene-expression patterns were analyzed in the primary tumors of patients with metastatic renal cell cancer by using cDNA microarrays. We used grossly dissected tumor masses that included tumor, blood vessels, connective tissue, and infiltrating immune cells to obtain a gene-expression "profile" from each primary tumor. Two patterns of gene expression were found within this uniformly staged patient population, which correlated with a significant difference in overall survival between the two patient groups. Subsets of genes most significantly associated with survival were defined, and vascular cell adhesion molecule-1 (VCAM-1) was the gene most predictive for survival. Therefore, despite the complex biological nature of metastatic cancer, basic clinical behavior as defined by survival may be determined by the gene-expression patterns expressed within the compilation of primary gross tumor cells. We conclude that survival in patients with metastatic renal cell cancer can be correlated with the expression of various genes based solely on the expression profile in the primary kidney tumor.
Adult↗
Variation in gene expression patterns in human gastric cancers.
Gastric cancer is the world's second most common cause of cancer death. We analyzed gene expression patterns in 90 primary gastric cancers, 14 metastatic gastric cancers, and 22 nonneoplastic gastric tissues, using cDNA microarrays representing approximately 30,300 genes. Gastric cancers were distinguished from nonneoplastic gastric tissues by characteristic differences in their gene expression patterns. We found a diversity of gene expression patterns in gastric cancer, reflecting variation in intrinsic properties of tumor and normal cells and variation in the cellular composition of these complex tissues. We identified several genes whose expression levels were significantly correlated with patient survival. The variations in gene expression patterns among cancers in different patients suggest differences in pathogenetic pathways and potential therapeutic strategies.
Adenocarcinoma↗
[Evaluation of blood flows inside hepatic tumors using color Doppler echography with galactose-based intravenous contrast medium "SH/TA 508" administration].
The purpose of this study is to evaluate hemodynamic characteristics of various hepatic tumors using color Doppler echography administered galactose-based intravenous contrast medium "SH/TA 508 (Levovist)". Subject were 9 cases of hepatocellular carcinomas, 5 cases of metastatic liver tumors and a case of hemangioma. We evaluated the characteristics of blood flows inside various hepatic tumors, and also evaluated the first pass through the hepatic tumors during administration of Levovist. The strongly pulsatile branched blood flows inside tumor and the slow-increased and plateau patterns were observed in the all cases of hepatocellular carcinomas, the weakly pulsatile blood flows surrounding tumor and the rapid-increased and slow-decreased patterns were observed in the cases of metastatic liver tumors, and the continuous blood streams in the margin of tumor and the slow-increased and slow-decreased pattern were observed in the case of hemangioma. These findings were characteristic in various hepatic tumors, and color Doppler echography enhanced by Levovist was very useful to distinguish hepatic tumors.
Carcinoma, Hepatocellular↗
Identification of high mobility group protein I(Y) as potential progression marker for prostate cancer by differential hybridization analysis.
One of the major problems in the diagnosis of localized prostatic tumors is to predict the aggressiveness of an individual tumor, which is presumably associated with chance to progression. In an attempt to find molecular markers that are specific for aggressive prostatic cancer cells, we compared steady-state mRNA levels of progressionally related prostatic tumors. The Dunning R-3327-H subline, a relatively benign rat prostatic tumor, was compared to the therefrom derived highly aggressive MatLyLu tumor by differential hybridization analysis. The differential screening revealed 26 complementary DNA clones that detected transcripts overexpressed in MatLyLu. Upon further screening on the entire panel of Dunning R-3327 sublines, it appeared that three clones (pBUS1, pBUS19, and pBUS30), detected transcripts specifically expressed in metastatic rat prostatic tumors. The expression pattern of pBUS19 and pBUS30 suggested a relation between these complementary DNAs. Nucleotide sequence analysis, however, could not yet substantiate this. Computer-assisted comparison of the DNA sequences revealed the presence of rat long terminal repeat-like repetitive elements in pBUS19. The differential expression of repetitive elements in progressionally related tumors is interesting, yet similar findings have not been reported in human malignancies. Nucleotide sequence analysis of pBUS1 indicated that this clone is identical or related to high mobility group protein I(Y), a non-histone nuclear protein. From recent studies it appeared that this protein might be implicated in replication and/or transcription processes and is induced in fast proliferating/undifferentiated cells. The overexpression of high mobility group protein I(Y) correlates rather with metastatic ability than with growth rate; hence it may serve as a valuable marker to identify progressionally advanced prostate cancer cells.
Animals↗