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PubMed2000

Testicular metastases from solid tumors: an autopsy study.

In a retrospective study of 738 consecutive autopsies of adult males with solid malignant neoplasms, five (0.68%) were shown to have metastatic deposits within the testis. These were metastases from bronchial carcinoma (three cases), melanoma (one case), and pancreatic endocrine carcinoma (one case). The mean age of the patients with solid tumors metastatic to the testis was 60 years (range, 32 to 83 years). The metastases from the solid tumors presented two patterns: destructive and/or focal interstitial. The destructive pattern was characterized by sheets of malignant cells that destroyed and replaced the seminiferous tubules. The interstitial pattern was characterized by tumor cells within the interstitium without involvement of the seminiferous tubules. All metastases showing the destructive pattern were macroscopically evident. Approximately 40% of the metastatic deposits were microscopic and showed a focal interstitial pattern. These cases are not easily identified unless a sufficient number of tissue blocks are sampled and carefully scrutinized. In 20% of the cases the metastatic deposits were bilateral. Improved diagnostic skills and treatment protocols in the last 11 years apparently have not significantly affected incidence, distribution, or the pattern of metastatic spread of solid tumors to the testis.

Adult↗

PubMed2004

Evaluation of P-glycoprotein, HER-2/ErbB-2, p53, and Bcl-2 in primary tumor and metachronous lung metastases in patients with high-grade osteosarcoma.

BACKGROUND: Investigation of the relation between primary tumor and metastatic disease is necessary for the identification of predictive factors for postrecurrence survival (PRS) in patients with recurrent osteosarcoma. METHODS: Cellular levels of P-glycoprotein, ErbB-2, p53, and Bcl-2 expression were evaluated in primary tumor biopsy and metachronous pulmonary metastasis specimens from 19 patients with high-grade osteosarcoma. Results were analyzed for differences between primary tumor and pulmonary metastases and for correlations between expression patterns and survival. RESULTS: Positive staining in lung metastases was noted in 68%, 53%, 32%, and 84% of patients for P-glycoprotein, ErbB-2, p53, and Bcl-2, respectively. These percentages were higher than those observed in primary tumor specimens for all genetic markers evaluated, with a significant difference in the percentage of patients with positive staining for P-glycoprotein (68% vs. 32%; P = 0.05) and a near-significant difference in the percentage of patients with positive staining for Bcl-2 (84% vs. 53%; P = 0.08). Patients with ErbB-2 expression in the primary tumor were more likely to have multiple metastases and shorter recurrence-free intervals compared with patients in whom ErbB-2 expression was not observed, whereas differences in P-glycoprotein, p53, and Bcl-2 expression were not related to differences in metastatic pattern. PRS was influenced by p53 expression levels in pulmonary metastases, with patients who had negative staining for p53 having a significantly better PRS rate relative to patients with positive staining for p53 (3-year PRS rate: p53-negative, 64%; p53-positive, 17%; P = 0.008). CONCLUSIONS: In the current study of patients with high-grade osteosarcoma, most patients exhibited increased cellular expression of P-glycoprotein, ErbB-2, and Bcl-2 in recurrent pulmonary metastases compared with primary tumor. Further studies aimed at investigating the relation between altered p53 expression in lung metastases and postrecurrence survival are recommended.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed1992

Ovarian and hepatic metastases of gastric carcinoma associated with high serum levels of human chorionic gonadotropin (hCG), alpha-fetoprotein (AFP), and carcinoembryonic antigen (CEA): a case report.

A 45-year-old woman who underwent gastrectomy for gastric carcinoma which had metastasized to the liver and ovaries, showed high serum levels of hCG, AFP and CEA. To locate the source, an immunohistochemical technique was utilized. HCG-producing cells were detected in poorly differentiated adenocarcinoma of a primary tumor and an ovarian metastatic site, and AFP-producing cells in poorly differentiated adenocarcinoma forming a medullary pattern of primary site and metastatic foci. CEA-producing cells were found diffused in primary tumor and metastatic foci. From the viewpoint of oncodevelopmental gene expression (Cancer Res 36:3423, 1976), it is interesting that the serum levels of these three tumor markers (hCG, AFP, CEA) were elevated simultaneously.

Biomarkers, Tumor↗

PubMed1980

Some special views in bone scanning.

Radionuclide bone scanning may sometimes demonstrate increased focal lesions with more or less symmetrical patterns. In the femoral neck, ribs, and axillary margins of the scapulae, these lesions may indicate pseudofractures. In the pelvis, irregular activity of the bladder may cause problems in differentiating between bladder diverticula and pelvic lesions. The routine use of imaging tables and traditional gamma camera views may lead to understating certain scintigraphic patterns and/or diagnosing these as metastatic disease. This article emphasizes the importance of certain special views in recognizing these patterns and making the proper diagnosis.

Adult↗

PubMed2003

Patterns of tumor spread and risk of fracture and epidural impingement in metastatic vertebrae.

Among patients with vertebral metastases, the identification of candidates for surgical stabilization has a limited basis in evidence. We retrospectively studied patterns of tumor spread (n = 756 vertebrae) and predictors of fracture and epidural impingement (n = 113 vertebrae) in infiltrated vertebrae with varying tumor histologies using sequential magnetic resonance images. Vertebral bodies were divided into 16 cells to map lesions. Fractured vertebrae were classified based on histology, level, fracture pattern, prefracture infiltration, and epidural impingement. Lesions were most often located within upper lumbar levels and the medial vertebral body. Fracture risk was greatest for upper lumbar (RR = 1.95; 95% CI: 1.12, 3.38) and undifferentiated tumors (RR = 7.36; 95% CI: 2.69, 20.12). A fourfold increase in fracture risk was noted in vertebrae with >80% body infiltration (HR = 4.5966; 95% CI: 1.66, 12.71). Symmetric fractures with fragments had the greatest risk of epidural impingement (p = 0.002). These findings have implications for management of patients with vertebral metastases.

Adult↗

PubMed1980

Histologic grading of prostatic carcinoma.

The histologic pattern of differentiation of prostate carcinoma and its grade of nuclear anaplasia was correlated with survival time in 197 patients with treated disease. In the histologic classification of prostatic carcinoma (Hohbach and Dhom, 1972) four patterns of growth are distinguished, which have different life expectancies. The survival probabilities of treated well and poorly differentiated adenocarcinoma do not show a significant difference when compared to age-matched male control groups. However, the survival probabilities in patients with cribriform and anaplastic carcinoma are significantly poorer. Even in metastatic carcinoma, the histologic pattern of differentiation seems to influence the survival probability. The grade of nuclear anaplasia (mild, moderate, marked) correlates well with the survival probability as well. The survival probability of patients with mild nuclear anaplasia does not differ from age-matched healthy males. Thus, a combined grading system (grades 0-5) is suggested which combines histologic pattern and nuclear anaplasia. In tumors with several structural patterns the most poorly differentiated one is evaluated. The reproducibility and validity of prognostic statements is more significant with the combined grading system than with only one single diagnostic criterion.

Adenocarcinoma↗

PubMed2005

Metastatic breast cancer presenting as linitis plastica of the stomach.

Early detection and treatment of breast cancer, leading to longer survival, has revealed the natural history of this disease process. Linitis plastica of the stomach is a potential long-term sequela of metastatic breast cancer. Here we present a case of metastatic breast cancer presenting as linitis plastica, as well as the treatment algorithm for this rare clinical entity. The world literature describes a clear pattern of linitis plastica for metastatic infiltrating lobular breast cancer and a discrete nodular pattern for infiltrating ductal cancer, in regard to metastasis to the stomach. To our knowledge, this is the first case of infiltrating ductal cancer presenting as linitis plastica of the stomach.

Breast Neoplasms↗

PubMed1993

Expression of platelet-endothelial cell adhesion molecule-1 (PECAM-1) during melanoma-induced angiogenesis in vivo.

Recent ultrastructural data indicate that tumor-induced angiogenesis involves polarized outgrowth of endothelial cells from established vessels into tumor parenchyma and interstitium. Efforts to define the cytoarchitecture of the angiogenic response and to ascertain molecular determinants of polarized endothelial migration have been impeded by lack of sensitive and specific immunologic markers for endothelium and vessel wall components. In this study, we utilized monoclonal antibody to platelet-endothelial cell adhesion molecule-1 (PECAM-1), a cell-cell adhesion molecule belonging to the immunoglobulin superfamily, to determine extent and patterns of angiogenesis in metastatic melanomas before (N = 7) and after (N = 3) induction of tumor-infiltrating lymphocyte responses provoked by administration of experimental melanoma vaccine. PECAM-1 proved to be a more reliable marker for angiogenesis than antibodies to von Willebrand Factor. Although both normal and tumor vessels exhibited prominent staining for PECAM-1, different patterns of endothelial reactivity were observed. Formation of new vessels was associated with i) PECAM-1 redistribution from a constitutive circumferential membrane pattern to a pattern restricted to cell-cell junctions; ii) formation of endothelial cords formed by cell-cell interactions; and iii) eventual development of open lumens. Vessels within inflamed (vaccine-treated) and non-inflamed melanomas did not differ with regard to patterns of PECAM-1 expression. Forming vessels of inflamed melanomas failed to express the cytokine-inducible activation marker, E-selectin. Although normal microvessels and reactive vessels of healing wounds demonstrated prominent staining for alpha 6 laminin receptor, vessels within melanomas showed apparently diminished expression.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1999

Development of an experimental ovarian tumor over a year in the rat.

Tumor growth, possible malignant transformation or metastatic propagation and hormonal patterns were evaluated over a year in luteoma induced by introducing an ovary into the spleen of ovariectomized 60 day-old rats. Sham castrated animals had a piece of muscle inserted into the spleen. Jugular blood samples were taken monthly. After a year animals were cycled and decapitated. Troncal blood was collected, autopsies were performed and luteoma were measured and fixed in 10% buffered formalin. Serum LH, FSH, PRL, estradiol and progesterone were measured. Serum inhibin content was determined in one month-old tumors-bearing animals and estrous rats as controls. After one year no external changes in tumor-bearing rats were observed, nor differences in body weight or mortality rates compared to Sham animals. Metastatic propagation was absent. Routine histological examination showed two types of tumors according to either granulosa or luteal cell predomination, tumor type did not determine hormonal patterns. However, a clear relationship between gonadotropin levels and tumor size was established. Low gonadotropins: Small tumors, 18.7% of cases and high gonadotropins: Large tumors, 81.3%. In Sham animals gonadotropins attained castrate levels and remained elevated until the end of the experiment. In the Small group no increases in gonadotropins or estradiol were detected, progesterone and PRL fluctuated. In the Large tumor group LH increased to Sham titers until month 7, then fell to initial levels, FSH augmented significantly as from month three and remained high up to month 5. No variations in either estradiol, progesterone or PRL were observed. Serum inhibin of one month-old tumor-bearing rats was significantly elevated, justifying the lack of FSH increase at this time point. We conclude that these luteoma do not suffer malignant transformation or induce metastases. They appear in two histological types. Tumor size depends on hormonal patterns. The delay in the initial increase and the sharp decrease observed in FSH in animals bearing Large tumors suggest a possible role for inhibin in this regulation.

Animals↗

PubMed1998

Distinguishing second primary tumors from lung metastases in patients with head and neck squamous cell carcinoma.

BACKGROUND: In patients with head and neck squamous cell carcinoma (HNSCC), a squamous cell carcinoma (SCC) in the lung represents either another primary tumor or a metastasis. This distinction greatly influences patient prognosis and could guide treatment strategies, but the nature of a solitary lung nodule is often difficult to discern by use of standard clinical and histologic parameters. Comparison of genetic alterations in the tumors could resolve this dilemma. METHODS: We compared paired tumors from 16 patients with HNSCC and a solitary lung SCC for loss (i.e., deletion) of loci on chromosomal arms 3p and 9p. Losses at these loci occur early during neoplastic transformation of the respiratory tract. DNA from microdissected tumors and normal tissues was subjected to polymerase chain reaction-based microsatellite analysis. An effort was also made to distinguish primary lung cancers from lung metastases on the basis of clinical and histopathologic features. RESULTS: In most cases, comparison of genetic alterations clarified the relationship between the lung tumor and the primary HNSCC. The paired tumors from 10 patients had concordant patterns of loss at all loci suggesting metastatic spread, whereas three paired tumors had discordant patterns of loss at all loci suggesting independent tumor origin. These observations were supported by the clinical and pathologic findings. CONCLUSIONS/IMPLICATIONS: In patients with HNSCC and a solitary SCC in the lung, microsatellite analysis provides a rapid genetic approach for discerning clonal relationships. In such patients, we found that a solitary SCC in the lung more likely represents a metastasis than an independent lung cancer. Microsatellite analysis could potentially be applied to any patient with multiple tumors, where tumor relationships are not clear on clinical, radiographic, or even histopathologic grounds.

Adult↗

PubMed1997

Differentiation between benign and metastatic cervical lymph nodes with ultrasound.

OBJECTIVE: The differentiation between benign and metastatic lymph nodes with ultrasound (US) is based primarily on the evaluation of size, shape, margin and internal echo structure. The aim of this study is to determine whether these parameters are reliable indicators and to correlate internal echo structure and histopathological findings. MATERIALS AND METHODS: Seventy-one nodes in 21 patients with pathologically proven oral squamous cell carcinoma were examined. The shortest diameter, the short/long diameter ratio (S/L ratio), margins and internal echo structure of the lymph node were evaluated by US. The internal echo structure was divided into six patterns: homogeneous hypoechoic, homogeneous hyperechoic, heterogeneous, eccentric hyperechoic, centric hyperechoic and anechoic pattern. In addition, internal echo structure was correlated with histopathological findings. RESULTS: In 71.4% of the metastatic nodes, the shortest diameter was more than 10 mm and the S/L ratio was higher than that of benign nodes (average 0.71). Eleven (84.6%) of the 13 lymph nodes with irregular margins were metastatic. Heterogeneous and anechoic patterns were observed in metastatic nodes, whereas homogeneous hypoechoic and eccentric hyperechoic patterns were present in benign nodes. On ultrasonography with the corresponding histopathological findings, echogenic areas in the homogeneous hyperechoic, heterogeneous and centric hyperechoic patterns of metastatic nodes proved to be necrosis or fibrosis. Eccentric hyperechoic areas in benign nodes corresponded to the hilus and surrounding fatty tissue. CONCLUSIONS: The shortest diameter, S/L ratio, margin and internal echo structure were considered to be critical indicators to differentiate between benign and metastatic nodes. Secondary changes caused by tumour infiltration, necrosis, or fibrosis should be assessed when metastatic lymph nodes are differentiated from benign ones by internal echo structure.

Adult↗

PubMed1992

Management of metastatic glomus jugulare tumors.

METASTATIC GLOMUS JUGULARE TUMORS (JUGULAR PARAGANGLIOMAS) ARE VERY UNCOMMON: consequently, no single report has been able to accurately describe their biologic or clinical behavior, and there are no established guidelines on caring for patients with these tumors. Identification of metastatic paraganglioma can be difficult because these tumors are known to occur synchronously, many other tumor types appear histologically similar to paragangliomas, and histologically the metastasis may not resemble the primary tumor. Immunohistochemistry, using neuroendocrine markers, and electron microscopy are the two most useful techniques available to identify definitely paragangliomas. A few studies have shown differences in the immunohistochemical staining patterns between benign and metastatic paragangliomas. We reviewed the literature and include two additional cases of metastatic glomus jugulare tumors in this article. We discuss the clinical management of these patients, the importance and usefulness of immunohistochemistry in characterizing these tumors, and their clinical outcomes.

Journal Article↗

PubMed1999

HPLC analysis of juzen-taiho-to and its variant formulations and their antimetastatic efficacies.

Our previous study demonstrated that the oral administration of Juzen-taiho-to resulted in a significant inhibition of the liver metastasis of colon 26-L5 cells as compared with the untreated control, without side effects. We attempted to investigate the relationship between the HPLC pattern (referred to as the fingerprint) of the formulation and its component crude drugs and the inhibition of tumor metastasis in order to obtain the optimal efficacy and constant quality of the formulation. Two Juzen-taiho-to formulations (batches #1 and #2), which were individually prepared using the same 10 crude drugs and the same preparation procedure, showed similar anti-metastatic effects and absorbance patterns by HPLC analysis. Some variant formulations of Juzen-taiho-to, in which one crude drug was substituted with other crude drugs from different sources or places of origin, exhibited reduced efficacy as compared with the original formulation, as well as differences in the fingerprint pattern compared with the original formulation. Juzen (Naimo-Ogi-->Kibana-Ogi), a variant formulation with the substitution of Astragali radix of a different origin and place of harvest, showed significant inhibition of the liver metastasis of tumor cells and a HPLC fingerprint pattern similar to that of the original formulation. Thus, HPLC fingerprint analysis of Kampo medicines may provide a useful basis for obtaining their optimal efficacy as well as constant quality of the formulation, although it has some problems and limitations, such as detectability by and sensitivity to UV absorbance.

Animals↗

PubMed1995

Keratins 7 and 20 as diagnostic markers of carcinomas metastatic to the ovary.

The most common carcinomas metastatic to the ovary that mimic ovarian primaries are colonic adenocarcinomas and endometrial carcinomas. Conventional histochemical staining procedures, even in combination with additional immunohistochemical assays, are of limited value in distinguishing between these metastases and primary ovarian carcinomas. In this study we investigated whether the application of monoclonal antibodies against keratins 7, 8, and 20 could help in differentiating between these categories. The reactivity patterns of 40 carcinomas metastatic to the ovary were compared with those of their primary carcinomas on the one hand and with various primary ovarian carcinomas and mesotheliomas on the other. Colon cancer metastatic to the ovary was keratin 7 negative and keratin 20 positive in 94% of the cases; in contrast, all primary ovarian carcinomas were keratin 7 positive and keratin 20 negative, with the exception of two cases of mucinous cystadenocarcinoma. Ovarian metastases of gastric cancer usually contained keratins 7 and 20. Metastases of endometrial cancer to the ovary and primary ovarian carcinomas usually showed similar keratin expression. We propose that keratin 7 and 20 antibodies may be of help to distinguish between primary ovarian carcinomas and carcinoma metastases in the ovary.

Adenocarcinoma↗

PubMed2006

Patterns of progression in gastrointestinal stromal tumor treated with imatinib mesylate.

BACKGROUND: Although most patients with gastrointestinal stromal tumor (GIST) treated with imatinib mesylate achieve remission or disease stabilization, a significant proportion show progressive disease (PD) with or without initial favorable responses. We evaluated and categorized the patterns of progression of metastatic or unresectable GIST treated with imatinib to identify the prognostic significance and contribution to further treatment decision-making. METHODS: We prospectively gathered clinical data from 62 GIST patients treated with imatinib mesylate (400 mg/day) over a median period of 26 months. Twenty-one of these patients showed evidence of PD based on Response Evaluation Criteria in Solid Tumor criteria. RESULTS: Four patterns of PD were defined: focal progression (FP, N = 4), general progression (GP, N = 6), new cystic lesion (NCL, N = 6) and new solid lesion (NSL, N = 5). The groups were found to differ in terms of time to progression and prior response to imatinib. The proportion of patients who responded to escalated doses of imatinib (600-800 mg/day) was significantly higher in NCL patients (P = 0.04). Overall survival and survival from the confirmation of PD were significantly better in NCL or FP patients compared with NSL or GP patients (P = 0.0157, P = 0.0013). CONCLUSIONS: We identified four patterns of disease progression based on radiographic criteria with different clinical characteristics and impact on survival. Knowledge of these patterns was relevant for early detection and may be helpful in further treatment decision-making.

Adult↗

PubMedDate not supplied

Time-dependent dephosphorylation through serine/threonine phosphatases is required for stable adhesion of highly and poorly metastatic HT-29 colon carcinoma cell lines to collagen.

Adhesion stabilization is a prerequisite for the long-term adhesion of circulating metastatic tumor cells, and tumor cells with different metastatic potential demonstrate distinct patterns of cell adhesion properties. An important event during formation of organ metastases is integrin-mediated extracellular matrix (ECM) binding that can initiate signal transduction events. Recently we reported that Ser/Thr kinases are involved in regulation of tumor cell adhesion. In the present study the influence of dephosphorylation by Ser/Thr protein phosphatases (PPases) on tumor cell adhesion was investigated. Pretreatment of poorly and highly metastatic human HT-29 colon carcinoma cells with the broad-range inhibitors sodium fluoride (NaF) and sodium pyrophosphate (PyroP) resulted in strong reduction in adhesion of HT-29 cells to various ECM components. Surprisingly, when specific Ser/Thr PPase inhibitors like tautomycin were used we found only a partial reduction in adhesion of highly metastatic HT-29LMM cells to collagen I but not to collagen IV. Other inhibitors did not inhibit adhesion, and poorly metastatic HT-29P were not affected by any specific Ser/Thr PPase inhibitors. Therefore, the effects of NaF on adhesion-mediated Tyr phosphorylation were investigated further. Pretreatment with this inhibitor led to a reduction in phosphorylation of focal adhesion kinase (FAK). In contrast, in cells grown adherent to tissue culture dishes, low concentrations of NaF increased FAK phosphorylation whereas high concentrations inhibited the amount of phosphorylated FAK. Although NaF inhibited adhesions it did not cause changes in cell morphology or detachment of cells from ECM. We hypothesize that dual-specific PPases may be involved in the regulation and establishment of new adhesive interactions in HT-29 cells, but they are not required for maintenance of stable adhesions to ECM.

Cell Adhesion↗

PubMed1977

Electrophoretic patterns for serum glycoproteins reflect the presence of human breast cancer.

We describe a group of glycoproteins that are synthesized and released by human breast tumors maintained in organ culture and similar glycoproteins released by a human breast carcinoma cell line (BT-20). The electrophoretic mobility of these glycoproteins on cellulose acetate is consistent with increased glycoprotein-staining material present in the alpha2- to beta-globulin region of serum glycoprotein electropherograms from patients with breast cancer. Moreover, after mastectomy, this glycoprotein material in serum decreases to concentrations seen in a control population of patients with benign breast lesions. Patients with proven metastatic breast cancer have patterns reflecting their clinical status: those who respond to treatment have glycoprotein electropherograms similar to the group of patients with benign breast lesions, while those who do not have increased amounts of alpha2- beta-glycoprotein. We believe serum glycoprotein measurements in breast-cancer patients reflect the presence of glycoproteins that are released by the malignant cells and enter the circulation.

Breast Neoplasms↗

PubMed1994

Antigenic profile of mucosal melanoma lesions.

Ten primary and 6 metastatic mucosal melanoma lesions were tested, utilizing the immunoperoxidase reaction with a panel of 26 monoclonal antibodies (MAbs). The latter included MAbs recognizing membrane-bound and cytoplasmic-melanoma-associated antigens, adhesion molecules and their receptors, and HLA Class-I and Class-II antigens. The melanoma lesions displayed differential reactivity with the panel of MAbs. Mucosal melanoma lesions differ from other types of melanoma in their antigenic profile, since they are the only type of melanoma to display a higher expression of p97 MAA, CEA-MAA and NGF-R in primary lesions than in metastatic ones. Furthermore, the pattern of HMW-MAA expression in mucosal melanoma lesions is different from that in nodular and uveal melanoma lesions and only partly resembles that observed in acral lentiginous melanoma lesions. Like other types of melanoma, mucosal melanoma lesions display a heterogeneous expression of HLA antigens, a selective loss of reactivity with some of the anti-HLA Class-I MAbs and a higher frequency of abnormalities in HLA Class-I antigen expression in metastatic than in primary lesions. Expression of HMW-MAA, 110-kDa MAA, p97 MAA, CEA-MAA, NGF-R and GD2 ganglioside in primary melanoma lesions was found to be associated with a poor prognosis. Although preliminary in nature, these results suggest that analysis of mucosal melanoma lesions with MAbs, in conjunction with information about the clinical course of the disease, will contribute to determine the biological and clinical significance of the distinct characteristics of the antigenic profile of mucosal melanoma lesions.

Antibodies, Monoclonal↗