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PubMed1991

Correlation between secretion pattern and metastatic potential from drug-treated 3LL tumor cell line.

In the present study, we described the effects of three different drugs, A23187 calcium ionophore (A23187), indomethacin (IND) and phorbol myristate acetate (PMA), on the secretion pattern and the metastatic potential in the low metastatic 3LL tumor cell line. The results evidence that a low molecular weight protein fraction is always secreted in an higher amount in drug treated cells than in untreated cells independently of the drug used. In addition to their effects on secretion pattern, the three drugs assayed enhance noticeably the metastatic rate in vivo of the 3LL cells. The data confirm our earlier observations showing that our high performance gel permeation chromatography (HPGPC) method is suitable for discriminating even between cells with a different degree (low and high) of metastatic potential by its chromatographic secretion pattern and that alterations in the secretion pattern from treated cells are related with changes in the degree of metastatic potential of these cells.

Animals↗

PubMed1991

Steroid hormone receptor activity of primary human breast cancer and pattern of first metastasis. The Breast Cancer Study Group.

A series of 258 breast cancer patients with known estrogen receptor (ER) status of the primary tumour who subsequently developed metastases were reviewed for site of first metastasis. In 188 cases progesterone receptor (PgR) data were also available. Univariate analysis showed metastatic patterns to differ statistically significantly related to ER status and (less pronounced) PgR status of the primary tumour. Patients with ER-positive tumours had bone metastases three times more often than patients with ER-negative tumours. With respect to PgR-positive and PgR-negative tumours this frequency differed by a factor of two. With regard to visceral metastases ER and PgR status were equally potent prognosticators, patients with receptor negative tumours having a 50% higher frequency of visceral metastasis than patients with receptor positive tumours. Assessment of metastatic patterns in relation to combined receptor status did not substantially enhance the discriminatory value of ER and PgR when assessed separately. Multivariate analysis showed that the observed differences in metastatic patterns were all attributable to differences in the ER status of the primary tumour, and were not influenced by age, menopausal status, axillary lymph node involvement, duration of disease-free interval (DFI), mode of postoperative treatment, or the PgR status of the primary tumour.

Abdominal Neoplasms↗

PubMed2026

Postoperative chemoradiotherapy in Wilms tumor with concurrent lung and lymph node metastasis.

BACKGROUND: An effective treatment strategy is essential for metastatic Wilms tumor (WT) management. To improve prognostic accuracy, this study examined metastatic patterns and key prognostic factors. METHODS: Children diagnosed with WT from 2010 to 2021 were identified from the SEER database. All patients underwent chemotherapy and surgical resection. Metastatic patterns, metastasis-related predictors, and prognostic factors were evaluated. RESULTS: Of the 1040 patients analyzed, 226 (21.7%) experienced lung metastasis, 31 (3.0%) liver metastasis, 6 (0.6%) bone metastasis, and 220 (21.2%) regional lymph node metastasis. Distant metastasis was associated with a higher incidence of lymph node metastasis (OR = 1.506, 95% CI 1.346-1.685, p < 0.001). Age 3-17 years (OR = 1.933, 95% CI 1.406-2.680, p < 0.001), left-sided (OR = 1.383, 95% CI 1.016-1.890, p = 0.040), bilateral (OR = 2.303, 95% CI 1.215-4.243, p = 0.009), and tumor size ≥135 mm (OR = 2.020, 95% CI 1.481-2.749, p < 0.001) were identified as predictors of metastasis. Both lymph node (p < 0.001) and lung metastasis (p < 0.001) were high-risk factors for WT. Radiotherapy provided long-term survival benefits for the metastatic population (p = 0.027), while postoperative chemotherapy showed better outcomes than preoperative or other strategies (p < 0.001). Further analysis demonstrated that the concurrent lung and lymph node metastasis group benefited more from postoperative chemoradiotherapy, with HRs of 0.226 (p = 0.028) for overall survival and 0.255 (p = 0.048) for cancer-specific survival. CONCLUSION: WT with concurrent lung and lymph node metastasis represents a distinct and aggressive metastatic phenotype associated with a significantly poor prognosis. Postoperative chemoradiotherapy may provide superior survival benefits for this high-risk population.

Humans↗

PubMed1979

Ganglioside patterns of metastatic and non-metastatic transplantable hepatocellular carcinomas of the rat.

In previous investigations, we correlated levels of sialic acid, gangliosides, and ganglioside glycosyltransferases with tumorigenesis over a 24-week continuum of growth of hepatocellular neoplasms of the rat induced by the carcinogen N-2-fluorenylacetamide. However, metastatic tumors developed only rarely and were not analyzed. To investigate surface changes associated with metastasis, well-differentiated and poorly differentiated hepatocellular carcinomas were transplanted to syngeneic recipient rats. From those, several metastatic and nonmetastatic isolates were obtained and compared. Both total and ganglioside sialic acid amounts in transplantable hepatomas were elevated above control liver values but were significantly lower for metastatic lines than for nonmetastatic lines. The nonmetastatic lines were characterized by ganglioside patterns depleted in the precursor ganglioside GM3 (sialic acid-galactose-glucose-ceramide) and elevated in the products of the monosialoganglioside pathway. In contrast, metastatic isolates exhibited a restoration of GM3 and nearer normal amounts of other gangliosides. The findings point to differences in sialic acid-containing glycolipids, comparing metastatic and nonmetastatic hepatocellular carcinomas, and further extend the concept that ganglioside alterations do not cause tumorigenesis but are the end result of a cascade of events which apparently continue beyond the onset of metastasis.

2-Acetylaminofluorene↗

PubMed1991

Cytokeratin expression patterns in metastatic transitional cell carcinoma of the urinary tract. An immunohistochemical study comparing local tumor and autologous metastases.

The cytokeratin (CK) expression patterns of local, ie, primary or recurrent, high-grade-malignant transitional cell carcinomas (TCCs) of the human urinary tract and autologous lymphogenic and hematogenic metastases (n = 33) were compared. Special attention was paid to CK expression in the tumor invasion front and other areas where tumor-stroma interaction occurred to visualize cell populations with a metastatic phenotype. For this purpose, polypeptide-specific monoclonal antibodies to CKs 4, 7, 8, 10, 13, 14, 16, 17, 18, and 19 were used, employing the immunoperoxidase method. Results show that: 1) An increased expression of CK8 and CK18 is seen in the TCC tumor cells at the interface with peritumoral stroma in the tumor invasion front and with intratumoral stroma ('interface phenomenon'). Other than reflecting a quantitative change, this phenomenon might be explained by unmasking of CK8 and CK18 epitopes occurring in these regions. 2) Although in general the expression of CK13 in local TCC is decreased with increase of histopathologic parameters for progression, ie, grade and stage, an extensive proportion of CK13-positive tumor cells still can be found in some TCCs, even in metastases. 3) Morphologically recognizable types of aberrant differentiation in TCC, i.e., pseudosarcomatous or squamous differentiation and marked loss of differentiation, show altered expression of many of the CKs studied.

Carcinoma, Transitional Cell↗

PubMed1991

Patterns of growth and metastases of induced pancreatic cancer in relation to the prognosis and its clinical implications.

To understand high malignancy of pancreatic cancer, the growth and metastatic patterns of pancreatic cancer induced in Syrian hamsters were examined. In this model, induced tumors resemble the human disease morphologically, clinically, biologically, and immunologically. In the current study, primary-induced cancer and transplants of pancreatic cancer cell line (PC-1) into the SC tissue or pancreas of homologous hosts were used. In the primary-induced pancreatic cancer, perineural invasion was the most common path (88%), followed by lymphogenic (31%) or vascular (2%) metastases. Inoculation of PC-1 cells into the pancreas resulted in 100% tumor take within 3 weeks. Of 19 intrapancreatic allografts, all showed peritoneal invasion, 5 (26%) liver metastases, 3 (16%) lymph node metastases, 17 (89%) perineural invasion, and none vascular invasion. Even microscopic tumors were found to metastasize primarily via perineural spaces. It was also demonstrated, for the first time, that cancer cells take this route to reach distant tissues, including the lymph nodes. Intraductal spreading occurred in both primary cancers and intrapancreatic allografts either continuously or discontinuously. The patterns of discontinuous intraductal tumor expansion imitated tumor multicentricity. Although perineural invasion was the most common feature of primary cancer and intrapancreatic allografts, lymphatic, hepatic, and vascular invasion and metastases usually occurred in advanced cases. Environmental factors seem to influence expansion and metastases, as evidenced by differences in growth and in metastatic patterns between SC and intrapancreatic allografts.

Animals↗

PubMed1977

Metastatic and histologic presentations in unknown primary cancer.

The patient with metastatic adeno- or undifferentiated carcinoma who presents with a cryptic primary is subjected to an extensive diagnostic search. These efforts apparently stem from the following assumptions: 1). The ultimately proven primary sites in such patients will occur with the same frequency as the most commonly occurring carcinomas (i.e., lung, breast, colon, prostate, etc.); and 2). Metastatic patterns and histologies seen at diagnosis are the same as for patients presenting with these more common tumors. Our data contradict these assumptions. For example, the most commonly occurring unknown primary was pancreas. Rarely occurring primaries included breast and prostate. Lung cancer was observed frequently, but the presentation was atypical because of the large proportion of female patients. In addition, the metastatic patterns at diagnosis were unusual for many of the ultimately proven primary sites. In an attempt to deal with these contradictions, a method to search for new relationships between primary site and metastatic-histologic presentations was employed. This method succeeded in placing the location of the primary cancer to above or below the diaphragm in 80% of the patients studied retrospectively. Tested prospectively in a small group of patients, the method appears to be clincally useful. Finally, in this study we have made the diagnosis, antemortem, of the primary cancer site (PCS) in only 30 of 264 patients. The failure to find the primary site, dispite extensive radiologic work-up, was disappointing to the authors, and emphasizes the difficulty of finding PCS antemortem. In our study pancreas and lung appear to be most common cryptic primary sites.

Abdomen↗

PubMed1991

The role of NK cells in the regulation of experimental metastasis in a murine lymphoma system.

This report describes the role of natural killer (NK) cells in regulating the localization of two closely related murine lymphomas (ASL1 and ASL1w) to various organ sites. These tumors are phenotypically similar yet differ in their overall malignancy and experimental metastatic pattern. Both tumors show similar patterns of migration in kinetic studies, however, they vary in their NK susceptibility. Cold target inhibition analysis and assessment of susceptibility to cytotoxic T lymphocytes (CTL) suggested that the NK resistance of ASL1 was due to the lack of expression of a relevant target structure(s) required for NK recognition. The role of NK cells in regulating the growth of the tumors in vivo was studied by altering NK cell levels in recipient mice prior to tumor injection. Neither NK cell depletion nor augmentation affected the growth of the NK resistant ASL1 tumor but NK depletion significantly shortened the mean survival time (MST) of recipients of the NK sensitive ASL1w tumor as well as changed its metastatic pattern; conversely, NK augmentation significantly increased the MST of ASL1w recipients. These data suggest that NK cells play a critical role in determining the metastatic characteristics of the ASL1w lymphoma.

Animals↗

PubMed1976

"Early" and "late" breast cancer: a unified concept for treatment.

Most women with "early" breast cancer have distant metastases by the time the primary growth comes to diagnosis. This observation is based upon the fact that these frequently appear despite successful removal of the primary growth, and given that they originate from the now no longer present tumour, the inescapable conclusion is that dissemination must have taken place prior to initial treatment. Failure to appreciate this rather obvious point results from shortcomings in available diagnostic technology, and inadequate usage of that which is available. Whether detected early or late, treatment of this disseminated cancer poses a common problem, and the various systemic methods are reviewed. Androgens, oestrogens, progestogens and single drug chemotherapy can, from time to time, produce useful results. By careful selection of patients with appropriate metastatic patterns, these methods may yield improved response rates up to 50% but, by and large, experience remains disappointing with across the board representative figures of perhaps 25% response being commonplace. Additionally, these methods are not without their side effects which can be distressing, and indeed on occasion life-threatening. Their short-comings have led to the development of cyclical combination chemotherapy as here reported. Cyclophosphamide, vincristine, 5-fluorouracil and methotrexate are administered for five consecutive days per month. The results obtained in 100 patients treated with this technique are compared with the authors' previous experience with norethisterone acetate and hypophysectomy. Whether the results are considered in total or broken down into prognostic categories such as predominant metastatic pattern, disease-free interval, or age, combination chemotherapy has a clear advantage over other techniques. Whilst this experience does not constitute a randomised trial, it is considered that the results are so superior to previous treatment techniques as to render such a study unnecessary or even unethical. It is proposed that combination chemotherapy should constitute the first line of treatment for overt advanced breast cancer. It is further proposed that its role should be explored at an earlier stage in the treatment of breast cancer. Before this can take place however, treatment must be made less demanding and less toxic. Further research is underway with these aims in mind.

Breast Neoplasms↗

PubMed1978

Growth patterns and metastatic behavior of human tumors growing in athymic mice.

The growth characteristics and metastatic behavior of human tumors growing in athymic nude mice were studied. Human tumor cell lines HEp-2 (carcinoma or larynx) and SW480 (colon carcinoma) were transplanted into athymic nude mice of BALB/c origin. Tumor cells (1 x 10(6) and 2 x 10(7)) were given either s.c. or i.p. Following s.c. injection tumors developed rapidly to become easily palpable with 2 weeks forming a s.c. tumor focus surrounded by a thick fibrous capsule. Animals with s.c. transplants were little affected by the growing tumor. At the time they were sacrificed at Day 34 (HEp-2) and 62 (SW480), a large part of the tumor was necrotic. Capsular infiltration and invasion of lymphatic vessels and perineural and perivascular lymphatic spaces were observed. Metastases to regional lymph nodes were seen in animals kept alive for up to 6 months. Following i.p. transplantation, tumors spread widely in the peritoneal cavity, invaded intraabdominal organs, and metastasized to mediastinal lymph nodes and lungs. Fifteen of 26 animals (60%) developed metastases. Necrosis of the i.p. growing tumors was minimal. All animals in this group died as a result of tumor growth.

Animals↗

PubMed1991

An evaluation of differences in prognosis, recurrence patterns and receptor status between invasive lobular and other invasive carcinomas of the breast.

One-hundred-and-seventy-one patients with invasive lobular carcinomas have been matched with 342 patients with non-lobular invasive carcinomas for lymph node stage, tumour differentiation and patient age on a one to two basis. The two groups were investigated for differences in prognostic factors, survival, disease-free interval, metastatic patterns, receptor status, response to endocrine therapy after distant metastases and bilateral cancer rates. Patients with lobular carcinomas survived significantly longer than patients with carcinomas of no specific type, particularly in survival from the time of diagnosis of distant metastases; lobular carcinomas more often responded to endocrine treatment for systemic disease. Lobular cancers had a significantly higher rate of local recurrence, particularly after treatment by excision and breast irradiation. No differences were found between the two groups with respect to regional or distant recurrence rates, distant organ involvement patterns, distant metastatic free intervals and receptor status. Bilateral cancer was more frequent in patients with lobular carcinoma.

Breast Neoplasms↗

PubMed1977

Metastatic disease of the parotid gland.

Metastatic lesions of the parotid gland represent the spread of a neoplasm from the primary site to parotid paraglandular, intraglandular, or parenchymal locations. These lesions are frequently difficult to differentiate from primary parotid gland neoplasms. The most common histologic type of neoplasm that metastasizes to the parotid gland is the melanoma. The melanoma is generally found superficial in its metastatic spread. Squamous cell carcinoma is also frequently found, but is usually intraglandular in its metastatic pattern. Although the melanoma and squamous cell carcinoma represent 80 per cent of the metastatic lesions involved in the parotid gland, a variety of other histologic types have been reported. The surgeon must be ready to deal with this complex problem when he enters into an exploratory operation. Even though vigorous treatment is carried out, the histologic types of neoplasms and the anatomic complexities of the area contribute to survival rates between 10 and 15 per cent over a five year period.

Carcinoma, Squamous Cell↗

PubMed2026

Circulating Tumor DNA Profiling Defines Risk Classification in Patients With Ewing Sarcoma: A Report From the Children's Oncology Group and the LEOPARD Study.

PURPOSE: Identification of discrete risk groups remains a high priority for patients with Ewing sarcoma (EWS). We sought to prospectively validate circulating tumor DNA (ctDNA) as a prognostic factor and develop clinical-molecular risk groups. METHODS: We conducted a prospective investigator-initiated biology study for patients with localized EWS (LEOPARD) and embedded ctDNA analysis into the North American frontline metastatic study AEWS1221. Eligible patients were younger than 50 years with newly diagnosed EWS. All patients provided a baseline blood sample for analysis, which was subjected to ultralow-pass whole-genome sequencing and hybrid capture panel sequencing for ctDNA quantification, fusion detection, and characterization of STAG2 and TP53 alterations. Serial ctDNA sequencing was conducted on a subset of patients in each study. We tested for associations between ctDNA burden and secondary genomic events, and clinical features and outcomes. RESULTS: One hundred forty patients with localized disease and 255 with metastatic disease provided evaluable pretreatment samples for ctDNA analysis. Elevated baseline ctDNA was associated with stage, tumor size, primary site, indeterminate pulmonary nodules, and metastatic pattern. Elevated pretreatment ctDNA burden was associated with inferior outcomes in patients with localized (n = 140, hazard ratio [HR] = 2.36, P = .032) and metastatic disease (n = 255, HR = 2.15, P = .001). Patients with metastatic disease and TP53 variants and/or persistent on-therapy ctDNA had dismal outcomes. Patients with localized disease, low ctDNA, small tumors, and favorable genomics had no events and constitute a novel low-risk group. Among patients with metastatic disease, those with lung-only disease, low ctDNA, and favorable genomics represent an intermediate-risk group. CONCLUSION: This study prospectively validates pretreatment ctDNA burden as prognostic in EWS. Risk groups that integrate ctDNA burden with clinical-molecular features differentiate patients with low-, intermediate-, and high-risk disease.

Journal Article↗

PubMed1978

Metastatic choroidal melanoma.

We studied the metastatic pattern of 41 patients initially referred with a primary choroidal melanoma who later developed widespread disease. In the order of frequency, the most common sites of metastatic involvement were the liver (56%), subcutaneous tissue (36.5%), and bone (7%). Whereas the median interval between enucleation and the onset of metastatic disease was approximately four years, in rare cases, metastases were diagnosed concurrently with a primary choroidal melanoma. Since patients with choroidal melanomas usually survive less than one year after the development of widespread disease, a metastatic examination should be done in all patients with pigmented choroidal tumors both before and after ocular therapy. From the data obtained in this and other studies on metastatic melanoma, a reasonable basic metastatic examination for choroidal melanoma patients should include a serum lactic dehydrogenase, a serum alkaline phosphatase, a routine chest X-ray, and a general physical examination.

Adult↗

PubMed1979

Diabetes insipidus and breast cancer.

Diabetes insipidus, resulting from metastatic involvement of the neurohypophysial system, is a rare complication of breast cancer. This review examined the clinical features, metastatic pattern, and radiological and postmortem findings of 39 breast cancer patients with this complication. All patients had polyuria and polydipsia, and all had evidence of advanced metastatic breast cancer. A high incidence of meningeal carcinoma carcinomatosis and/or sellar metastases was observed. In view of the anatomical proximity of the posterior pituitary to the dura mater and the sella turcica, our findings suggest that metastases to the neurohypophysis can occur not only as a result of hematogenous dissemination of malignant cells, but also from direct tumor extension and/or invasion from adjacent structures. Although satisfactory symptomatic relief can be obtained with vasopressin tannate, complete resolution of the diabetic insipidus syndrome was evident only in those patients who had achieved control of the underlying breast disease.

Adult↗

PubMedDate not supplied

Natural killer sensitivity of tumor cells isolated from primary and metastatic lesions of four Bomirski melanoma variants.

Natural killer (NK) sensitivity of melanoma cells isolated from primary and metastatic lesions of four Bomirski melanoma variants was compared. The hamster melanomas differed in their growth rate and metastatic pattern. We found that during tumor growth of all the variants tested, NK sensitivity of melanoma cells at the metastasis formation stage was significantly lower in both primary and metastatic tumors than in cells isolated from primary tumors at transplantation. In the case of Ma, Ab and Ab-455, NK sensitivity of primary tumor cells was higher than that of the cells isolated from metastatic deposits. These data obtained from a spontaneous metastasis tumor model argue for the role of NK cells in preventing metastatic spread of Bomirski melanomas studied.

Animals↗

PubMed1992

Prognostic value of pathological patterns of lymph node positivity in squamous cell carcinoma of the vulva stage III and IVA FIGO.

Lymph node positivity in invasive squamous cell vulvar cancer implies a severe decrease in survival rates. Pathological lymph node positivity covers a wide range of metastatization patterns. In the present investigation the nodal positivity of 53 patients affected by Stage III and IVA invasive vulvar squamous cell carcinoma has been carefully evaluated and correlated with survival. Number, size of the metastasis inside the node, intracapsular or extracapsular site of the metastasis, and immune response of the positive nodes were considered. Cancer-related survival has been obtained for the whole study group (53 cases), for the patients with monolateral node positivity (36 cases), and for the patients showing only one positive node (19 cases). The diameter and the site of the metastasis were significantly correlated with survival in all three groups studied. Patients showing an intracapsular positivity or a size of metastasis less than 5 mm had a 5-year cancer-related survival of almost 90%, while patients showing a metastasis larger than 15 mm or an extracapsular site had a 20% survival. The results demonstrate that patients affected by invasive squamous cell vulvar cancer with positive nodes can be divided into two groups with a significantly different survival according to the histopathological pattern of lymph node invasion.

Aged↗

PubMed1992

Breast carcinoma: periodicity in presentation of metastatic tumour growth in the axilla.

The clinical value of assessment of tumour load in the axilla in the treatment of breast cancer patients has stood the test of time. Much information is available on its extent and characteristic distribution but, in contrast, little is known of the biological factors that may control the timing of the metastatic phenomenon. There is recent circumstantial evidence that such factors may exist and this prompted the present detailed study of axillary metastases from a series of 437 consecutive cases of breast carcinoma. Evidence of such factors was found here also: the excess of micrometastases in cases coming to operation in the second half of the year was highly significant (P less than 0.001) and is consistent with a synchronized start to the metastatic process. The total metastatic pattern in the material further indicated that the process may show periods of inactivity, i.e. periods when new colonies are not recruited. Mechanisms controlling this periodicity could theoretically be light-mediated, opening up new possibilities in the development of anti-metastatic treatment regimes.

Axilla↗