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PubMed1986

[Choriocarcinoma of the stomach].

A 55-year-old Japanese man was admitted to our hospital in January 1985 complaining of epigastralgia. Radiologic and endoscopic examinations showed gastric carcinoma, but biopsy specimens taken by surgery showed the histologic pattern of choriocarcinoma. On autopsy, multiple metastatic sites wer observed, and histological examination of the primary and metastatic sites revealed choriocarcinoma. Primary gastric choriocarcinoma may develop from gastric cancer by retrodifferentiation.

Biopsy↗

PubMed1983

Different patterns of lectin binding and cell surface sialylation detected on related high- and low-metastatic tumor lines.

We have analyzed cell surface-bound carbohydrates in two different model systems for metastasis composed of closely related tumor cell lines with differing metastatic potential. The first system studied was that of the DBA/2-derived T-lymphoma lines (Eb/ESb) and some recently established sublines of ESb with altered metastatic behavior (ESb-M and ESb-MR). The second system consisted of the highly metastatic MDAY-D2 cells, a wheat germ agglutinin-resistant low metastatic subline MDW40, and two metastatic revertants from the latter. The cells were stained with fluorescein isothiocyanate-conjugated lectins and analyzed by flow cytofluorography. All low-metastatic tumor lines expressed receptor sites for the lectins soybean agglutinin (SBA) and Vicia villosa (VV). The metastatic lines had the respective lectin binding sites blocked by sialic acid (SA). A good correlation was found within the cell lineages Eb leads to ESb leads to ESb-M leads to ESb-MR and MDAY-D2 leads to MDW40 leads to MDW40M1 between reactivity of SBA and VV and metastatic potential. The amount of neuraminidase-accessible SA was similar for all cell types (except MDW40) indicating differences in the positioning of SA. For high-metastatic ESb cells, the sialylation of SBA and VV receptor sites was paralleled by a relative decrease of SA associated with receptor sites for peanut agglutinin. Low-metastatic Eb cells, in contrast, had their peanut agglutinin receptor sites sialylated but expressed asialylated SBA and VV receptor sites. Eb cells were also found to have 2-fold higher activities in galactose-specific sialyltransferases. It is proposed that the differences in positioning of SA on the cell surface leading to masking or unmasking of terminal sugars could influence the metastatic potential of tumor cells.

Animals↗

PubMed1982

[Radiological and telethermographic diagnosis of breast lymphomas (28 cases)].

Twenty eight patients with histologically proven primary or secondary malignant lymphoma of the breast were evaluated by mammography and telethermography between 1968 and 1980 at Istituto Nazionale Tumori of Milan. This histological type is rather unusual and poor is the radiological literature on the matter. The roentgenographic findings showed especially isolate nodes with clear-cut or irregular outline, multiple displasic lesions or diffuse inflammatory-like disease. Because of such a variety of radiological matters, diagnosis is often uncertain. No significant difference between primary or metastatic disease was seen in radiological patterns of non-Hodgkin lymphomas. In the three cases of Hodgkin's lymphoma radiological findings suggested inflammatory disease. Telethermography was usefully associated showing, in the majority of cases, high hyperthermia also in "benign" mammographic patterns.

Adult↗

PubMed1995

The diagnostic value of thrombomodulin immunolocalization in serous effusions.

OBJECTIVE: To test the value of an antithrombomodulin monoclonal antibody as a diagnostic tool in detecting mesothelial cells and in differentiating mesothelioma from other malignant effusions. DESIGN: Thrombomodulin is a thrombin receptor that is distributed on surfaces where an anticoagulant activity is expected, including mesothelium. Antigen expression was studied by immunocytochemistry in 226 peritoneal and pleural exudates. RESULTS: The antigen was found in 33 of 33 mesotheliomas, 35 of 35 reactive effusions, 57 of 145 carcinomatous fluids, and in one case of angiosarcoma among seven metastatic nonepithelial tumors. Three distinct staining patterns were demonstrated: (1) thin cell membranes in benign mesothelial cells; (2) thick cell membranes in mesotheliomas; and (3) cytoplasm in carcinomas. All squamous cell carcinomas had demonstrable thrombomodulin, suggesting that antigen expression likely correlates with squamous differentiation. CONCLUSIONS: Thrombomodulin is of diagnostic utility in distinguishing mesothelioma from adenocarcinoma, provided the characteristic "thick membrane" pattern is present, but it should be used in panels with other markers of mesothelial and/or epithelial differentiation.

Adenocarcinoma↗

PubMed1993

Electron microscopy in the evaluation of melanocytic tumors.

Melanoma is the "syphilis of malignant tumors", said one of my favorite mentors (Dr Jerome Wollman, Wadsworth VA Hospital, Los Angeles, California). What syphilis is to clinicians, melanoma is to surgical pathologists. By light microscopy, melanoma, especially in its metastatic form, can exhibit any imaginable pattern, can be amelanotic, and the immunostaining can be negative or equivocal. The present review deals with the features of both classic and aberrant forms of melanosomes. In addition to melanosome morphology, spectrum of ultrastructural features of usual and unusual histological variants of melanoma are described and illustrated. Finally, the role of immunoelectron microscopy is discussed briefly.

Humans↗

PubMed1996

[Adhesion molecules and carbohydrates in cancer metastasis].

Cancer metastasis is a complex phenomenon consisting of several sequential steps: invasion of primary sites, entry into blood or lymphatic vessels, transport, lodgement, extravasation, and growth at the target sites. These steps are achieved by peculiar interactions between tumor cells and host tissues. We developed several sublines from rat ascites hepatoma AH7974 that displayed different substrates adhesiveness and lung metastatic potential and demonstrated that the expression of 62 and 56kDa laminin-like substances with alpha-galactose residues on tumor cell surfaces is one of the determinants associated with the lung-colonizing potential of these cells. So, we expanded our investigation to detect the metastasis/prognosis-related carbohydrate antigens in primary cancers of the breast, lung, stomach, and large intestine by lectin histochemistry or immunohistochemistry. The results showed that certain types of carbohydrate antigen expressions in cancer cells are profoundly related to not only the mode of metastatic spread and the organ distribution pattern of metastasis but also the prognosis of cancer patients. Lymphatic metastasis was related to the expression of mucin core type carbohydrates (Tn antigen and Tn-like antigens) in common, whereas there were no conspicuous similarities in the hematogenous metastasis-related carbohydrates among the cancers. The expressions of blood group antigens such as ABH, Lewis and MN including their precursors appeared to be strong prognostic indicators of these cancers, although the relation of these antigens to each cancer varied. These results suggest that adhesion molecules and/or carbohydrates are one of the determinants of cancer metastasis and prognosis at least in part.

Animals↗

PubMed1996

[Is radiotherapy still the first choice treatment in spinal metastases from breast cancer?].

The skeletal system is a frequent site of metastatic involvement from breast cancer, whose pattern of spread is such that cure becomes practically impossible. The best palliation with the minimum discomfort for the patient must therefore be the major objective. With an increasing number of reports about major surgical procedures for spinal metastases, we reviewed our series of patients submitted to radiotherapy. Of 2,189 breast cancer patients, we selected 28 who might have been potential candidates for surgical resection (with lesions only in the spine, only one or no more than three contiguous bodies involved and no other metastases). All these patients had been treated with 20 or 30 Gy plus systemic (chemo, hormone, or both) therapy. Follow-up revealed that all of them had developed new metastases outside the treated field within one year. Local control was achieved in 68% of patients and 75% of them had stable or better performance status at 3 months. Median survival was 36 months. From our analysis, even patients with a so called "solitary lesion" seem not to have a better prognosis than others. We conclude that radiotherapy is still the method of choice to treat vertebral metastases from breast cancer. The role of surgery should be limited to patients with neurologic compression or severe mechanical instability.

Breast Neoplasms↗

PubMed1976

[Malignant vascular tumors of the lung (cytologic and histologic parallels)].

Analysis of 78 observations (including 6 of the author's own) of primary malignant vascular tumours of the lung, showed that these tumours had no characteristic clinicoroentgenological features; in this connection the question of their preoperative cytological diagnosis is of importance. The retrospective collations of cytological and histological data in 8 patients made it possible to establish criteria of cytological diagnosis of similar tumours. For the first time in the Soviet literature a suggestion was put forward that basing on the data of cytological investigations it is possible in a number of cases to give a detailed verification of tumours of the lung with presumable indication to hemangioendothelioma, angiosarcoma, or hemangiopericytoma. Metastases of malignant vascular tumours of other localizations in the lung are of analogous cytological pattern. correct diagnosis of primary of metastatic tumour can be made only if all the complex of clinico-roentgenological and cytological data are taken into account.

Adult↗

PubMed1992

Tumor-associated carbohydrate antigens in primary pulmonary adenocarcinomas and their metastases.

To better understand the metastatic behavior of pulmonary adenocarcinoma, we studied the differences in carbohydrate antigens between primary tumors and their metastases using three monoclonal antibodies (FH-2 defining Lewis [Le]x, AH-6 defining Le(y), and FH-6 defining sialyl Le(x-i)) on 56 autopsy cases (including 15 cases in which primary tumors were surgically resected) and 116 cases of surgically resected pulmonary adenocarcinoma. Metastatic lesions were divided into two groups according to the route of metastasis: group 1 comprised lymphatic metastases, such as lymph node and contralateral lung metastases, and group 2 comprised hematogenous metastases, such as extrathoracic spread. Both primary tumors and metastatic lesions with well-differentiated glandular patterns showed higher positive rates for Le(y) than the poorly differentiated lesions. Such a difference in the antigen expression in relation to tumor differentiation was barely demonstrated for Le(x) and sialyl Le(x-i). Discordance in antigen expression between primary and metastatic lesions (ie, positive primary tumors with negative metastatic lesions and negative primary tumors with positive metastatic lesions) was observed in the following order of frequency: extrathoracic metastatic lesion, contralateral lung, mediastinal lymph node (N2), and ipsilateral peribronchial and hilar (N1) lymph nodes. This study revealed increased biologic diversity of pulmonary adenocarcinoma in cell surface antigens following tumor progression, especially in extrathoracic metastasis.

Adenocarcinoma↗

PubMed2001

Uroplakin as a marker for typing metastatic transitional cell carcinoma on fine-needle aspiration specimens.

BACKGROUND: Immunohistological markers specific for a single type of epithelium are rare. Recently, urothelium tissue-specific genes were cloned. The genes encoded a family of transmembrane proteins, uroplakins, that are expressed only in urothelial mucosa. Using uroplakin antibodies on paraffin-embedded tissue, a previous study demonstrated positive staining in 66% of metastatic transitional cell carcinoma (TCC) cases and negative staining in all other tumors (including breast, ovarian, lung, and gastrointestinal carcinomas) tested. The current study addresses the diagnostic value of uroplakins in conventional fine-needle aspiration (FNA) material in establishing a diagnosis of metastatic TCC. METHODS: Representative slides from 27 FNA cases of metastatic TCC and 52 non-TCC carcinomas were collected. The avidin-biotin-peroxidase method was utilized, using polyclonal antiuroplakin as the primary antibody on 95% ethanol-fixed, Papanicoloau-stained direct smears. RESULTS: Twenty-five of 27 metastatic TCC cases (93%) were found to stain positively for uroplakin with a superficial membrane/microluminal staining pattern. A few cells with diffuse membranous staining also were noted in 48% of the positive metastatic TCC cases. The superficial membrane/microluminal staining pattern was not observed in any of the non-TCC carcinomas. However, approximately 6% of these cases (3 of 52 cases) did show rare tumor cells with diffuse membranous staining. CONCLUSIONS: The application of uroplakin antibodies to 95% ethanol-fixed FNA direct smears has improved the sensitivity of the antibody for metastatic TCC while maintaining a specificity comparable to that of paraffin-embedded tissue. The authors believe that these antibodies have diagnostic potential in cytopathology in the evaluation of metastatic TCC.

Adult↗

PubMed2006

[Breast cancer: analysis of treatment quality in Germany 2004: retrospective survey by Arbeitsgemeinschaft Gynäkologische Onkologie (AGO)].

The Organgruppe Mamma der Arbeitsgemeinschaft Gynaekologische Onkologie (AGO) conducted a nationwide 3-phase analysis of the care structure and standard of therapy given to patients with breast cancer from 2002 (4th quarter) to 2004 (4th quarter). The analysis includes 1069 patients from 257 institutions; 34% with early breast cancer and 66% with metastatic disease. No reliable data on the pattern of care of these patients have been published to date in Germany. The extent to which national and international therapy recommendations were implemented in routine clinical practice was unclear. Evaluation of the data shows that treatment based on the guidelines is now being implemented very reliably in certain sectors. This is of particular relevance to the pattern of adjuvant treatment in early breast cancer. At that time 68 % of the patients received an anthracyclin based chemotherapy and in addition 18% received an anthracycline and taxane based chemotherapy. Participation in clinical trials peaked with 30% in the neoadjuvant setting. The problem with metastatic breast cancer is the complexity of the interdisciplinary treatment involved. The present analysis conducted by the AGO was the first attempt to analyse the treatment given to metastatic patients and to systematise the approach to treatment. The fundamental problem remains, irrespective of the stage of the tumour, namely that too few patients are treated in randomised clinical studies.

Antineoplastic Agents↗

PubMed2000

Accuracy of axillary MR imaging in treated breast cancer for distinguishing between recurrent tumour and treatment effects: does intravenous Gd-DTPA enhancement help in cases of diagnostic dilemma?

AIM: To evaluate the sensitivity and specificity of axillary magnetic resonance imaging (MRI) in symptomatic patients, who had previously been treated for breast cancer, compared with clinical outcome after a minimum of 1 year. METHODS: One hundred and five patients underwent axillary MRI examinations and were diagnosed as axillary tumour, metastatic tumour, treatment effect or normal. RESULTS: At MRI, 48 patients had axillary tumour, 51 had metastatic tumour (37 had both), 27 had treatment effect and 22 were normal. At outcome (median follow-up, 484 days), 54 patients were positive for axillary tumour, 59 for metastatic disease (40 had both), 21 had treatment effect alone and 18 were clear. Magnetic resonance imaging showed 89% sensitivity, 100% specificity and 94% accuracy for recurrent axillary tumour, and 85% sensitivity, 98% specificity and 90% accuracy for metastatic tumour. Soft tissue plaques were the commonest axillary disease pattern seen (37). Small volume soft tissue plaques gave the most diagnostic difficulty. Non-dynamic enhancement with intravenous Gadopentetate dimeglumine (Gd-DTPA) in a subset of 34 patients improved sensitivity for axillary tumour from 40 to 74%, and improved diagnostic confidence in 11 patients (32%). Magnetic resonance imaging had a positive management impact leading to treatment alteration in 45 patients, 43 of whom had recurrent axillary and/or metastatic tumour. CONCLUSIONS: Tumour plaques were the commonest pattern of recurrent axillary disease. Forty-eight percent of the patients had metastatic deposits identified by MRI. Magnetic resonance imaging had excellent specificity (100%) and good sensitivity (89%) for recurrent axillary tumour compared with outcome at 1 year, which was improved by non-dynamic administration of Gd-DTPA in 32% of the subset who received it.

Adult↗

PubMed2005

Is older age associated with a worse prognosis due to different patterns of care? A long-term study of 1346 patients with glioblastomas or brain metastases.

BACKGROUND: The objective of this study was to find out whether the worse prognosis of older patients with primary or metastatic brain tumors can be explained by different patterns of care compared with younger patients. METHODS: A data base that included 430 patients with glioblastomas and 916 patients with brain metastases who underwent radiotherapy at the author's hospital between 1980 and 2000 was analyzed. Patterns of care were compared for different age groups using the chi-square test. RESULTS: In both patient groups, age turned out to be an independent risk factor. Older age was associated with worse overall survival. Independent of the cut-off age (< 50 years vs. > or = 50 years, < 60 years vs. > or = 60 years, < 65 years vs. > or = 65 years, and < 70 years vs. > or = 70 years), there were no statistically significant differences between the age groups concerning the use of different imaging modalities (computed tomography scans vs. magnetic resonance imaging), type of surgery (none vs. biopsy vs. resection), waiting time for radiotherapy (< median vs. > or = median), radiotherapy treatment planning (simulator-based vs. computer-based), use of radiation sources (cobalt unit vs. linear accelerator), and fractionation protocols (conventional vs. modified). When the recruitment period of 21 years was divided into 3 intervals, impressive changes with regard to the patterns of care became apparent. However, the changes were seen similarly throughout the different age groups. CONCLUSIONS: Older age did not limit access to state-of-the-art patterns of care in neurooncology. Patients participated in medical progress irrespective of their age. The worse prognosis of older patients with glioblastomas or brain metastases was not determined by age-related differences in access to health care.

Adult↗

PubMed1997

Specific degradation of subendothelial matrix proteoglycans by brain-metastatic melanoma and brain endothelial cell heparanases.

One of the many features of the malignant phenotype, in vitro and in vivo, is elevated heparanase production and activity. Using in vitro model systems, we examined the capacity of murine (B16B15b) and human (70W) brain-metastatic melanoma cells to degrade the subendothelial matrix produced by endothelial cell monolayer cultures. B16B15b and 70W melanoma cells solubilized sulfated matrix proteoglycans at levels significantly higher than their parental lines (B16F1, MeWo). Sulfated matrix proteoglycans were rich in heparan sulfate (HSPGs), with minor amounts of chondroitin and dermatan sulfates. When matrix HSPGs were treated with pronase and alkaline borohydride to cleave the core proteins, the resulting glycosaminoglycan chains (GAGs) had an estimated M(r) of approximately 2.7 x 10(4) Da, with a minor subpopulation possessing an M(r) of approximately 4.5 x 10(4) Da. After their incubation with brain-metastatic melanoma cells, new HS fragments with lower M(r) estimated at approximately 9 x 10(3) Da were detected. This confirms action in these cells of heparanase, which is capable of cleaving GAGs at specific intrachain sites and releasing fragments of a relatively high M(r). The pattern of HSPG degradation by brain-metastatic melanoma cells differed from that of less metastatic parental cells or cells metastatic to organs other than the brain. Moreover, supraadditive levels of heparanase activity were found when brain endothelial cells were coin-cubated with brain-metastatic melanoma cells in equicellular amounts. Cooperative interactions between heparanases from tumor and endothelial sources in the invasion process are suggested and their potential mechanisms discussed.

Animals↗

PubMed2001

Intermittent androgen deprivation: update of cycling characteristics in patients without clinically apparent metastatic prostate cancer.

OBJECTIVES: To update the cycling characteristics and patterns of treatment in patients receiving intermittent androgen deprivation (IAD) for clinically localized and recurrent prostate cancer. METHODS: We report our experience with 61 patients treated with IAD. Thirty-four patients had received no prior treatment, and 27 had developed recurrent disease after previous local therapy. No patient had clinically apparent metastatic disease before the initiation of therapy. The mean and median serum prostate-specific antigen (PSA) level before treatment was 25.3 ng/mL and 16.0 ng/mL, respectively (range 0.5 to 190 ng/mL). For each cycle, androgen deprivation was continued until PSA became undetectable or a nadir level was reached. Patients were then observed without treatment, and therapy was reinstituted after the serum PSA value reached a predetermined level. Patients were no longer eligible to cycle off treatment when their serum PSA increased despite ongoing androgen deprivation or if any objective evidence of disease progression was present on imaging studies. RESULTS: Follow-up ranged from 7 to 60 months (mean 30) from the start of treatment. Patients received from one to five treatment cycles (median two), with a median cycle length of 14 months. The median nadir serum PSA level during androgen deprivation was 0.01 ng/mL and was reached within an average of 6 months (range 4 to 9) after beginning treatment. Patients spent an average of 45% of the time not receiving therapy, but the time off therapy decreased as the number of treatment cycles increased. Five patients (8.1%) demonstrated progressive disease, with a median time to progression of 48 months. When examining the cycling characteristics of these patients, no consistent pattern of failure emerged. CONCLUSIONS: IAD appears to be a viable treatment option in select patients with localized prostate cancer. With each consecutive cycle, the amount of time the patient was not receiving therapy decreased, despite achieving a low nadir PSA. Longer follow-up with more patients failing IAD will be required before clear patterns of failure emerge in these patients.

Aged↗

PubMed2005

The immunohistochemical profile of the primary and metastatic carcinoma of the clitoris: a case report.

We describe the immunohistochemical profile of rare primary squamous carcinoma of the clitoris metastasizing to the bilateral inguinal lymph nodes. Several antigens were assessed immunohistochemically (pRb1, p16INK4A, cyclin D1, cdk4, estrogen receptor (ER), progesterone receptor (PR), androgen receptor (AR), p53, Ki-67, p27KIP1, PTEN, hMLh1, phospho-AKT, collagen IV, leptin and CD90) in both tumors. All the antibodies applied revealed a staining pattern that is typical of primary and metastatic carcinomas. Cyclin D1-cdk4 complex was overexpressed, whereas there was no p16INK4A immunostaining. Moreover, both tumors expressed positivity for p53 protein, but were negative for estrogen and progesterone receptors. The proliferative activity of cancer, assessed by MIB-1 Proliferative Index, amounted to 25% either for primary or for metastatic tumors. As a conclusion, immunohistochemical assessment of various cell-cycle-associated molecules yield clues as to their possible function during the process of spread of rare neoplasm originating from the clitoris.

Aged↗

PubMed1980

The role of vascularization in the formation of echographic patterns of hepatic metastases: microangiographic and echographic study.

An experimental microangiograhic and echographic study was carried out on metastatic autopsy livers which were also examined histologically. Relationships between the echographic pattern and vascularization are explored. In most cases, hypervascular lesions correspond to hyperechogenic patterns, while hypovascular lesions furnish hypoechogenic images.

Angiography↗

PubMed1992

Somatic mutation during metastasis of a mouse fibrosarcoma line detected by DNA fingerprint analysis.

Metastatic nodules were examined by DNA fingerprint analysis. The probes used, Pc-1 and Pc-2, detect mutations as shifts in bands of the minisatellite loci which are dispersed among chromosomes. Four clonal lines of a fibrosarcoma from an F1 mouse (C57BL/Ka x C3H/He) were selected for various metastatic potentials upon inoculation into syngeneic mice. These four lines exhibited many extra bands resulting from recombination and/or DNA slippage, indicating accumulation of mutations during the successive passages in mice. One of the four, a 505 cell line which had been passaged extensively in vitro and consisted of a heterogenous population, was inoculated into thirteen syngeneic mice, and gave rise to six lung metastatic nodules in two mice. All the nodules showed band-patterns distinct from one another, although nodules within a given mouse tended to show similar patterns. When a genetically tagged 505-05-01 clone was analyzed, three of nine metastatic nodules obtained also revealed new bands. These results strongly suggest that somatic mutations occur at a high frequency during metastasis, providing direct evidence of genetic instability of the tumor cells.

Animals↗