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PubMed2006

Patterns of EphA2 protein expression in primary and metastatic pancreatic carcinoma and correlation with genetic status.

EphA2 is a transmembrane receptor tyrosine kinase that functions in the regulation of cell growth, survival, angiogenesis, and migration and EphA2 targeting has been proposed as a novel therapeutic strategy for neoplasms that overexpress this protein. EphA2 overexpression has been correlated with increased invasive and metastatic ability in pancreatic cancer cell lines. However, the patterns of EphA2 expression in human pancreatic cancers and associated metastases is unknown, as are the genetics of EphA2 in this tumor type. We collected clinicopathologic data and paraffin-embedded materials from 98 patients with primary and/or metastatic pancreatic cancer and performed immunohistochemical labeling for EphA2 protein. EphA2 protein immunolabeling was found in 207 of 219 samples (95%). The expression was predominantly cytoplasmic, although predominant membranous staining was observed in a minority of cases. When evaluated specifically for labeling intensity, primary and metastatic carcinomas were more strongly positive compared to benign ducts and PanIN lesions (P < 0.00001 and P < 0.01, respectively) and poorly differentiated carcinomas were more strongly positive for EphA2 than well and moderately differentiated tumors (P < 0.005). When primary carcinomas without metastatic disease were specifically compared to carcinomas with associated metastatic disease, the advanced carcinomas showed relatively less strong positive labeling for EphA2 (P < 0.008). Moreover, decreased EphA2 labeling was more commonly found in liver (P < 0.002), lung (P < 0.004) or peritoneal metastases (P < 0.01) as compared to distant lymph node metastases (P < 0.01). Genetic sequencing of the tyrosine kinase domain of EPHA2 in 22 samples of xenograft enriched pancreatic cancer did not reveal any inactivating mutations. However, EPHA2 amplification was found in 1 of 33 pancreatic cancers corresponding to a lymph node metastasis, indicating EPHA2 genomic amplification may underlie EphA2 overexpression in a minority of patients. Our data confirms that EphA2 is overexpressed in pancreatic cancer, but suggests a relative loss of EphA2 in co-existent pancreatic cancer metastases as well as a role for EPHA2 in organ specific metastasis.

Adult↗
PubMed1991

Imaging pattern of radiolabelled lymphokine-activated killer cells in patients with metastatic malignant melanoma.

In patients with metastatic malignant melanoma the distribution patterns of radiolabelled lymphokine-activated killer (LAK) cells were investigated. Peripheral mononuclear cells (PMC) were isolated from six patients. LAK cells were generated by culturing PMC in complete medium containing 1000 U interleukin (IL)-2/ml and labelled with indium 111 before retransfer. We obtained scans at 2.5, 24, 48 or 96 h after injection with a high resolution gamma-camera. Intravenously injected LAK cells distributed to the lungs, liver, spleen and bone marrow. External tumour detection of known lymph node and bone metastases was successful in four. It failed in one patient with a solitary lung metastasis and in another patient with subcutaneous metastases. Our results suggest that LAK cells show tumour homing, providing a direct interaction between tumour and cytotoxic cells. We conclude that PMC seem to retain their ability to migrate after IL-2 stimulation and 111In-labeling. This technique may be helpful for kinetics studies or external detection of metastases in patients with malignant melanoma.

Adult↗
PubMed1984

Survival and patterns of recurrence in cervical cancer metastatic to periaortic lymph nodes (a Gynecologic Oncology Group study).

Ninety-eight of 621 evaluable patients (16%) with cervical cancer enrolled into Gynecologic Oncology Group protocols were found to have periaortic lymph node metastases at staging laparotomy or at exploration for definitive operative management. As expected there was a progressive increase in the prevalence of periaortic metastases including 5% of 150 patients with Stage IB, 16% of 222 patients with Stage II, and 25% of 135 patients with Stage III. Periaortic lymph node metastases in the absence of pelvic lymph node metastases was an infrequent occurrence in patients so evaluated. The median survival of patients with periaortic metastases was 15.2 months with a survival probability of 25% at 3 years. The median duration of survival following recurrence was only 5 months. Recurrences were divided approximately equally between the pelvis and distant sites.

Adenocarcinoma↗
PubMed2003

In vivo monitoring of tumor relapse and metastasis using bioluminescent PC-3M-luc-C6 cells in murine models of human prostate cancer.

We used the bioluminescent human prostate carcinoma cell line PC-3M-luc-C6 to non-invasively monitor in vivo growth and response of tumors and metastasis before, during and after treatments. Our goal was to determine the utility of a luciferase-based prostate cancer animal model to specifically assess tumor and metastatic recurrence in vivo following chemotherapy. Bioluminescent PC-3M-luc-C6 cells, constitutively expressing luciferase, were implanted into the prostate or under the skin of mice for primary tumor assessment. Cells were also injected into the left ventricle of the heart as an experimental metastasis model. Weekly serial in vivo images were taken of anesthetized mice that were untreated or treated with 5-fluorouracil or mitomycin C. Ex vivo imaging and/or histology was used to confirm and localize metastatic lesions in various tissues initially detected by images in vivo. Our in vivo data detected and quantified early inhibition of subcutaneous and orthotopic prostate tumors in mice as well as significant tumor regrowth post-treatment. Local and distal metastasis was observed within seven days following intracardiac injection of PC-3M-luc-C6 cells. Differential drug responses and metastatic tumor relapse patterns were distinguished over time by in vivo imaging depending on the metastatic site. The longitudinal evaluation of bioluminescent tumor and metastatic development within the same cohorts of animals permitted sensitive and quantitative assessment of both primary and metastatic prostate tumor response and recurrence in vivo.

Animals↗
PubMed1984

Ploidy pattern of megakaryocytes in patients with metastatic tumors with and without paraneoplastic thrombosis and in controls.

In order to measure megakaryocyte DNA content in a greater number of well-defined patients, the use of bone marrow aspirates obtained postmortem is a basic requirement. We could show that the distinction between the ploidy classes in DNA histograms is possible until 18 h postmortem. Thus, bone marrow aspirates obtained up to 12 h after death can be expected to give reliable results. Megakaryocytes of the following patient groups were studied: 15 patients with metastatic tumors and paraneoplastic thrombosis, 15 patients with metastatic tumors without paraneoplastic thrombosis and 10 controls. A higher ploidy of the megakaryocytes was found in all 30 patients with metastatic tumors, independently of whether these patients suffer from thrombosis or not. Higher megakaryocyte ploidy, however, is correlated with a larger cytoplasmic mass of megakaryocytes, which leads to an increased platelet production. Besides an overcompensation for increased platelet consumption, a mitogenic or thrombopoietin-like factor produced by the tumor itself must be considered.

Adult↗
PubMedDate not supplied

[Non-metastatic osteosarcoma of the extremities: the pattern of relapse as a function of the type of treatment and of the modulation of the radiological follow-up of the thorax].

The authors analysed the patterns of recurrence of osteosarcoma of the extremities treated between 1959 and 1989 either with surgery alone (1959-71) or with combined surgery and adjuvant (1972-82) or neoadjuvant chemotherapy (1983-89). In a total of 452 patients with recurrent osteosarcoma, the initial site of metastasis was the lung in 88% of cases independently of the type of treatment received. The mean period of onset of pulmonary metastasis differed according to the type of treatment performed: 8 months for patients treated with surgery alone; 15.9 months for those treated with adjuvant chemotherapy and 20.3 months for patients treated with neoadjuvant chemotherapy. The incidence of metastases appearing within 12 months of FU was 87%, 56% and 21% respectively. In a most recent and effective neoadjuvant protocol (66% DFS), the incidence of recurrence owing to pulmonary metastasis during the first year of FU was 2% and as much as 75% of all recurrences were concentrated in the following 18 months. Surgery for pulmonary metastasis in patients undergoing chemotherapy was performed in 54 cases with secondary healing in 14 (26%). On the basis of these results the authors suggest a scheme of radiological follow-up for patients with osteosarcoma of the extremities treated with neoadjuvant chemotherapy with intensified controls (every 2 months) during the period with the highest risk of recurrence (13-20 months) and four-monthly controls during the first year and after 31 months of FU. In order to increase the efficacy of FU controls during the high-risk period, the a. propose using CT controls instead of chest X-rays at months 14, 20 and 26.

Adult↗
PubMed1994

Carbon dioxide-enhanced ultrasonography of liver tumors.

CO2 gas-enhanced ultrasonography was performed in 37 patients (47 studies) for the purpose of detecting small tumors and evaluating differential diagnosis. With conventional ultrasonography, 62 lesions were identified in 25 patients with HCC, 13 tumors were identified in eight patients with hemangioma, and multiple tumors were found in four patients with metastatic adenocarcinoma. CO2-enhanced ultrasonography detected five additional hemangiomas, 12 additional nodules in HCC, and the same number of metastatic nodules. The patterns of CO2 enhancement were characterized as homogeneous, heterogeneous, rim, internal spotted, negative, and mixed (more than one pattern in one lesion). The rim enhancement pattern was found to be specific for hemangioma. The internal spotted enhancement pattern was found exclusively in HCC. All the lesions that demonstrated negative enhancement were treated HCC. All the metastatic tumors demonstrated the mixed rim and internal spotted enhancement pattern. We suggest that CO2-enhanced ultrasonography is a useful tool in detecting small liver tumors. It can also help in the differentiation among various hepatic tumors.

Adenocarcinoma↗
PubMed1999

Image analysis of papillary thyroid carcinoma fine-needle aspirates: significant association between aneuploidy and death from disease.

BACKGROUND: Papillary thyroid carcinoma is the most common thyroid malignancy in the U.S. As many as half of patients with papillary carcinoma present with cervical lymph node metastases at the time of diagnosis. Metastatic disease involving cervical lymph node tissue has not historically been proven to correlate with a more aggressive course; however, distant metastases worsen prognosis. METHODS: Diagnostic fine-needle aspiration (FNA) smears from 26 primary and metastatic papillary carcinomas underwent Feulgen reaction and were studied by image analysis to determine DNA pattern, proliferation index, and the percentage of cells with DNA content >5C. The medical records of all the patients were reviewed for metastatic disease pattern and survival data. For metastatic pattern, two groups were defined: 1) confined to thyroid/local lymph node metastases/soft tissues of the neck involved by tumor, and 2) distant metastases. RESULTS: Among the 26 patients, 16 had "nonaggressive" DNA patterns described as diploid, abnormal diploid, or tetraploid, and 10 had "aggressive" DNA patterns described as aneuploid. Only 2 of the 16 patients in the "nonaggressive" DNA pattern group developed distant metastases, whereas 5 of the 10 patients in the aneuploid group developed distant metastatic disease. In addition, none of the 16 patients with "nonaggressive" DNA patterns died of disease, whereas 3 of the 10 individuals with DNA histograms interpreted as aneuploid did die of metastatic disease complications. CONCLUSIONS: Aneuploidy identified by image analysis of FNA of papillary thyroid carcinoma is significantly associated with death from papillary carcinoma (log rank test, P=0.027).

Adolescent↗
PubMedDate not supplied

Imaging diagnosis--pulmonary metastases in New World camelids.

The radiographic appearance of pulmonary metastatic disease from carcinoma is described in a llama and an alpaca. In one, a diffuse miliary pattern was seen. In the other, a more atypical unstructured interstitial pattern was recognized. Metastatic pulmonary neoplasia in camelids may assume a generalized miliary or unstructured pattern.

Adenocarcinoma↗
PubMed1997

Heterogeneity of DNA ploidy pattern in carcinoma of the gallbladder: primary and metastatic sites.

There are few detailed reports on the heterogeneity of the nuclear DNA ploidy pattern in carcinoma of the gallbladder. We studied twelve autopsied cases who died of extended gallbladder carcinoma. Multiple samples were taken from the primary site (Pri), from direct invasion of the liver (Hinf), from hematogenous metastasis to the liver (H), from lymphatic metastasis (LN) and from peritoneal dissemination (P). The DNA ploidy pattern was investigated by image cytometry. Heterogeneity of the DNA ploidy pattern in Pri, Hinf, H, LN and P was found in 7/11, 2/10, 5/10, 2/6 and 3/6 cases, respectively. Aneuploidy was more frequently found in Hinf than at the Pri. The DNA index of Hinf was significantly higher than that of Pri. Several stemlines, with different quantities of DNA, were found in Pri. Most of these stemlines were also observed in other sites. These facts may suggest that polyclonal cancer cells rather than one cancer cell or monoclonal cancer cells of a Pri metastasize or infiltrate, and that various polyclonal cancer cells proliferate to different degrees under different circumstances.

Aged↗
PubMed1999

Pattern of progression and survival in hormonally treated metastatic prostate cancer.

BACKGROUND: Patients with prostate cancer generally respond to androgen ablation therapy, but progression to androgen-independence is frequently observed. To further evaluate disease progression, the pattern of progression and survival in hormonally treated metastatic prostate cancer was examined. METHODS: One hundred and ninety-three patients with untreated metastatic prostate cancer (TxNxM ) who received endocrine therapy between 1986 and 1995 were included in the present study. The pattern of progression was evaluated in these patients. RESULTS: One hundred and eighteen of the 193 patients (61.1%) had disease progression: 33 had local progression, 73 had distant progression and 12 had distant with local progression. Patients with only local progression had a longer interval to disease progression and longer survival than those with distant progression. The interval from disease progression to death in patients with local progression was longer than in those with distant progression. The patients whose prostate-specific antigen (PSA) had not been normalized 3 months after the start of endocrine therapy had a tendency to progression either into the prostate or into distant sites. Patients with extent of disease (EOD) scores of 3 and 4 progress, especially to distant sites, after endocrine treatment. CONCLUSIONS: In untreated metastatic prostate cancer, patients with a poor response of PSA levels and patients with a high volume of bone metastasis (i.e. EOD 3, 4) were in the high-risk group for progression, especially to distant sites. Progression into distant sites was a poor prognostic factor for patients with recurrence to endocrine therapy.

Aged↗
PubMed2004

Non-metastatic stage IV nasopharyngeal carcinoma patients: analysis of the pattern of relapse and survival.

BACKGROUND AND PURPOSE: The objective of this study is to analyze the mode of recurrence patterns and survival of our 96 non-metastatic stage IVA and IVB nasopharyngeal carcinoma (NPC) patients. PATIENTS AND METHODS: A total of 234 previously untreated, histologically confirmed non-metastatic NPC patients were treated in our department between 1993 and 2001. Among them 96 patients (41%) were staged as IVA or B disease. All patients were uniformly staged using the fifth edition of AJCC/UICC staging system. There were 76 male and 20 female patients. Their ages ranged from 9 to 72 years (median age: 43.5). Histopathological diagnosis was WHO 2 and 3 in 89 (93%) patients. All patients were treated with external radiotherapy and 77 out of 96 patients (80%) with stage IV disease received either concomitant or neoadjuvant cisplatin based combined chemotherapy regimens. Median follow-up time was 30 months (range: 4-101 months). RESULTS: At the time of this analysis, 60 (62%) patients were alive and 48 of them were free of disease. Local recurrence rate was found to be significantly higher in stage IVA patients (28 vs. 11%, P=0.02) and distant metastasis rate was significantly higher in stage IVB patients (40 vs. %8, P=0.0001). The 3 year overall (OS), disease free (DFS), loco regional relapse free (LRRFS) and distant metastasis free survival (DMFS) rates were 71, 74, 77 and 94% for stage IVA and 60, 46, 77 and 58% for stage IVB patients, respectively. Three year LRFS rates for stage IVA and IVB were 77 and 89%, respectively (P=0.1). Age older than 40 years was found to be statistically significant adverse prognostic factor both for OS (P=0.01) and LRRFS (P=0.005) in univariate analysis. Advanced N status was an unfavorable prognostic factor both for OS (P=0.03), DFS (P=0.0004) and DMFS (P=0.0003). DMFS was adversely affected by the presence of cranial nerve palsy at diagnosis (P=0.01), advanced T status (P=0.03) and advanced N status (P=0.0003). In univariate analysis treatment with chemotherapy was found to be an unfavorable prognostic factor for DMFS (P=0.02). According to the multivariate analysis, older age (>40 year of age) was a significant independent prognostic factor for OS (P=0.02), DFS (P=0.05) and LRRFS (P=0.01). Patients with advanced N status had worse OS (P=0.03), DFS (P<0.0001) and DMFS (P=0.07). Patients treated with chemotherapy as an adjuvant to radiotherapy had tended to have a better DFS (P=0.04). CONCLUSIONS: The local relapse was the major cause of failure in patients with stage IVA disease, and distant metastasis was the predominant treatment failure in stage IVB patients. While stage IVA patients may benefit more intensive local treatment strategies, stage IVB patients definitely need more systemic treatment.

Adolescent↗
PubMed1995

Patterns of failure following bone marrow transplantation for metastatic breast cancer: the role of consolidative local therapy.

PURPOSE: The purpose of this analysis is to evaluate the patterns of failure and the role of local therapy in conjunction with bone marrow transplantation (BMT) for metastatic or recurrent breast cancer. METHODS AND MATERIALS: Between June 1986 and November 1991, 46 patients with hormone unresponsive metastatic or recurrent breast cancer underwent high dose chemotherapy (HDC) with hematopoietic stem cell support. The most commonly used preparative regimen consisted of thiotepa (750 mg/m2), cisplatin (150 mg/m2), and cyclophosphamide (120 mg/kg) followed by autologous BMT. Consolidative surgery or irradiation was considered in patients whose cancer responded to BMT and had localized sites of disease. RESULTS: Six patients (13%) died of BMT-related complications. Of the remaining 40 patients, 22 were candidates for consolidative therapy, and 18 of those patients received consolidative irradiation (17 patients) or surgery (1 patient) to one or more sites. At median follow-up of 27 months (range, 20-78), 12 of 18 (67%) patients have continuous local control at the 22 consolidated sites (1 of 4 controlled at chest wall sites, 7 of 8 at regional nodal sites, 7 of 7 at localized bone sites, and 1 of 3 at lung/mediastinal sites). Toxicity of consolidative irradiation was mainly limited to myelosuppression in 6 of 17 patients. Two patients did not complete the consolidative local therapy, one because of hematologic toxicity and one because of rapid systemic tumor progression during treatment. CONCLUSION: In patients with localized areas of extravisceral metastases, consolidative irradiation is feasible with acceptable hematologic toxicity. Consolidative irradiation can result in continuous local control, especially in isolated bone metastases and in regional nodal sites; however, the advantage is less clear in patients undergoing consolidative irradiation for chest wall failures. Because distant visceral metastases still remain a major site of failure after this HDC regimen, a more effective systemic therapy is needed. Consolidative local treatment should be considered in future HDC/BMT protocols for metastatic breast cancer, especially in localized nodal and osseous sites.

Actuarial Analysis↗
PubMed1997

Inhibition of highly metastatic FBJ-LL cell migration by ganglioside GD1a highly expressed in poorly metastatic FBJ-S1 cells.

For clarification of the functions of gangliosides on tumor metastasis, examination was made of the ganglioside patterns of poorly metastatic FBJ-S1 and highly metastatic FBJ-LL cells. FBJ-S1 cells expressed GM3 and GD1a, whereas FBJ-LL cells expressed GM3 and slightly expressed GD1a. The capacity for FBJ-LL cells to migrate was ten times that of FBJ-S1 cells, but decreased by a half by pretreatment with GD1a. GD1b or GT1b had the same effect as GD1a, and synthetic sialyl compounds to a lesser extent, suggesting that gangliosides contain more than two sialyl residues to inhibit the migration of FBJ-LL cells.

Animals↗
PubMed1990

[Immunohistochemical study of the localization and distributional patterns of CA 19-9 and CEA in primary and metastatic nodal lesions of gastrointestinal cancer].

The localized and distributional patterns of CA 19-9 and CEA have been immunohistochemically examined in 22 nodal metastasis from antigen-producing gastrointestinal cancers. CA 19-9 and CEA were found in 95% and 45% of these metastasis respectively. The same distributional and localized patterns in the metastasis as were found in the primary lesions amounted to 77% and 41% for CA 19-9, and 45% and 27% for CEA, respectively. These results suggest that the capability of producing CEA is absent or suppressed in the metastatic lesions, whereas the capability lesion but also in the metastatic lesions as well.

Antigens, Tumor-Associated, Carbohydrate↗