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PubMed1998

Lectins in the vulva. II. Vulvar intraepithelial neoplasia and squamous cell carcinoma.

This study used lectins as histologic probes to determine the cell surface oligosaccharide expression in different grades and types of vulvar intraepithelial neoplasia (VIN). Lectin binding patterns in metastasizing and non-metastasizing squamous cell carcinomas (SCCs) of the vulva were also compared to correlate lectin binding patterns with metastatic potential and other clinical/tumor characteristics. Twenty cases each of VIN epithelium, metastasizing SCC, and non-metastasizing vulvar carcinoma were randomly chosen from the pathology archives. Sixteen lectins were used to probe individual terminal oligosaccharide residues in formalin-fixed, paraffin-embedded tissue specimens from these cases through an indirect immunohistochemical technique. There were no differences in lectin binding patterns between the different histologic subtypes of VIN. In addition, there were no consistent differences between metastasizing and non-metastasizing primary tumors and no major differences in staining patterns between nodal metastases and the corresponding primary tumors. Furthermore, there was no identifiable correlation between lectin binding patterns and subsequent survival or local or regional recurrence; however, lectin staining of invasive tumor cells did appear to be related to local invasiveness. In addition, positive PNA binding was found to be a constant finding in each of the VIN and invasive SCC cases, confirming that the T-antigen becomes unmasked during the process of vulvar carcinogenesis. However, poorly-differentiated areas consistently showed absent lectin binding, suggesting loss of specific glycosyl transferase activities. In addition, the blood group "A" antigen appears to be lost during the process of tumorgenesis, although the blood group "O" antigen appears to be preserved.

Carcinoma in Situ↗

PubMed1982

[Distribution of lung cancer metastases. I. Combination and frequency of organ metastases].

The distribution of metastatic tumors of 935 lung cancers with blood borne metastases has been analysed. The frequency of affected organs decreased in the following sequence: liver, bone, adrenal, brain, lung, kidney, thyroid gland, pancreas, spleen and heart. In cases with only one metastatic affected organ the frequency of brain and lung metastases is greater than the frequency of liver, bone and adrenal metastases. Especially in cases with two different affected organs the pair combination of liver and bone metastases as well as of brain and adrenal metastases is evident, however, combined brain and bone metastases and brain and liver metastases rarely occur. The distinct pattern of metastatic distribution in the body supports the evidence of the "soil" hypothesis. Seldom affected organs rarely shows a strong metastatic involvement and go hand in hand with many other affected organs. In autopsies the duration of cancer disease is much longer in cases without metastasis or small metastatic involvement than in cases with many affected organs. Therefore, the generalization of metastatic spread mainly depends on the malignancy of tumors and to a less extent on the duration of cancer disease.

Adrenal Gland Neoplasms↗

PubMed1997

Pancreatic metastases: CT assessment.

We report the CT appearance of pancreatic metastases and describe their features in relation to the originating primary tumor. We also discuss some limitations in their differential diagnosis and report some theories explaining the pathogenesis of their occurrence. A total of 20 cases (9 males and 11 females) of pancreatic metastases were diagnosed at staging or follow-up of oncologic patients. All patients were evaluated with CT before and after contrast medium administration and had subsequent pathologic confirmation. In 1 case metastases were located solely in the pancreas; in 6 there was only another metastatic location, and in the remaining 13 there was diffuse spread throughout the body. Two of our patients exhibited a multinodular metastatic involvement of the pancreas, 11 had a solitary nodule or mass, and the remaining 7 had a diffusely enlarged pancreas, without any signs of focal disease. All but one of the solitary lesions measured more than 4 cm. In 2 cases a metachronous malignancy was detected at follow-up. Primary malignancies were located: 6 in the lungs, 2 on the skin (melanomas), 3 in breasts, 2 in the ovaries, 3 in the colon, 1 in the stomach, 2 in the kidney, and 1 the thyroid. Our findings confirm the existence of three patterns of metastatization to the pancreas: large solitary masses, multinodular lesions, and diffuse enlargement of the pancreas without focal signs at CT. In contrast to other studies, the large solitary lesion was our most frequent encounter, therefore making differential diagnosis vs primary cancer difficult. Metastases tended to repeat the imaging pattern of the primary. Nevertheless, we wrongly diagnosed pancreatitis due to a small nondetected metastasis, pseudo-cystic mass as a mucinous cystadenocarcinoma, conglomerate of peripancreatic lymph nodes, and a solitary pancreatic mass diagnosed as primary pancreatic cancer. Thus, when faced with a solitary pancreatic lesion at follow-up, histologic diagnosis is strongly recommended. In 2 cases changes in aspect and size were related to therapy.

Adult↗

PubMed1999

Multifactorial analysis of the survival of patients with distant metastasis arising from primary extremity sarcoma.

BACKGROUND: Despite optimal multimodality limb-sparing therapy for extremity soft tissue sarcoma (STS), a significant number of patients develop distant metastasis. The objective of this study was to analyze patterns of metastatic disease and define prognostic factors for survival in a large group of patients followed prospectively at a single institution. METHODS: Between July 1, 1982, and June 30, 1996, all adult patients admitted to the Memorial Sloan-Kettering Cancer Center with primary extremity sarcoma were treated and prospectively followed. Patients who developed distant metastases constituted the study group. Prognostic factors were analyzed for postmetastasis survival. These included both factors related to the primary tumor and factors related to the pattern of metastasis. Postmetastasis survival was modeled using the Kaplan-Meier method. Statistical significance was evaluated using the log rank test for univariate analysis and the Cox proportional hazards model for multivariate analysis. RESULTS: During the study period, the authors admitted and treated 994 patients with primary extremity STS. The median follow-up was 33 months. Distant metastasis developed in 230 patients (23%). Median survival after distant metastasis was 11.6 months. The lungs were the first metastatic site in 169 patients (73%). Other first sites of metastasis included the skin and soft tissues of the head and neck, trunk, and extremities. There was no statistically significant difference in survival between patients with pulmonary and those with nonpulmonary metastatic disease. In multivariate analysis, resection of metastatic disease, the length of the disease free interval, the presence of a preceding local recurrence, and patient age > 50 years all were significant predictors of postmetastasis survival. Other factors that defined the primary tumor, including histologic grade, depth, and microscopic margins, were not associated with postmetastasis survival. CONCLUSIONS: Despite optimal multimodality therapy, 23% of the patients in this series with primary extremity sarcoma developed distant metastasis. Median survival after metastasis was approximately 1 year. After metastasis, the independent favorable factors that are associated with patient survival include resection of the metastases, a long disease free interval, the absence of preceding local recurrence, and patient age < 50 years. Although a definitive conclusion regarding the benefit of resection can be made only with a randomized clinical trial, these data suggest that resection of metastatic STS may contribute to patient survival, which in some cases may be long term.

Adolescent↗

PubMedDate not supplied

Changes of phenotypic characteristics of variants derived from Lewis lung carcinoma during long-term in vitro growth.

Two cultured cell clones derived from Lewis lung carcinoma (3LL), which have been shown to differ in their metastatic potential, were studied for their phenotypic stability in vitro. Several growth properties (lag-phase duration, doubling time, saturation density, cell shedding, plating efficiency) have been monitored for more than three years. The ability to induce primary tumors and metastasis, together with the response of cultured cells to adriamycin and bleomycin, have also been evaluated over the same period. The results show that the pattern of metastatic heterogeneity of the two clones is maintained during the serial passages in vitro, although the most actively metastatic clone (C108) displayed a reduced lung colony-forming ability at late passages. Furthermore, both clones exhibited an increasing sensitivity to adriamycin, while no changes were observed in the response to bleomycin. The present data suggest a phenotypic instability of tumor clones adapted to tissue culture conditions and, in particular, that the inherent chemosensitivity of tumor cells may change during long-term culture.

Animals↗

PubMed2003

Bone scan in initial staging of prostate cancer.

Bone scans of 64 patients with newly diagnosed prostate cancer were retrospectively analysed. Metastases were present in 29 patients (45%). In 75% of these cases, the pattern was manifeastly metastatic. The third threshold has high negative and positive predictive values. The topography of metastatic lesions is in favour of a systemic spread. There were no metastatic cases with a PSA level under 10 ng/ml. Multiple IAU and intense IAU are the most specific patterns of metastatic lesions. Also, focal lesions on sacroiliacs are also in favour of metastatic origin. The distribution of metastases is globally similar to that of the bone marrow in adult and systemic spread is the most probable. Staging bone scan must be reserved to patients with PSA level greater than 10 ng/ml, poorly degree of differentiation and advanced clinical stage.

Aged↗

PubMed1979

Combination chemotherapy of metastatic breast cancer: a randomized trial comparing the use of adriamycin to that of Vinblastine.

Two regimens of chemotherapy for metastatic breast cancer were compared in a randomized controlled fashion. Regimen 1 consisted of cyclophosphamide, vinblastine, methotrexate and 5-fluorouracil (CVMF). Regimen 2 consisted of cyclophosphamide, adriamycin, methotrexate and 5-fluorouracil (CAMF). The patient population consisted of both black and white postmenopausal females who had not received any prior chemotherapy. Objective responses were observed in 25/57 patients treated with CVMF and in 28/51 patients treated with CAMF. Neither race nor choice of chemotherapeutic regimen affected prognosis, although there were differences in the pattern of metastatic involvement between the two racial groups. The median duration of survival of patients who responded to therapy has not yet been reached but will be in excess of 12 months.

Adult↗

PubMed2002

Factors affecting progression-free survival in hormone-dependent metastatic breast cancer patients receiving high-dose chemotherapy and hematopoietic progenitor cell transplantation: role of maintenance endocrine therapy.

We retrospectively analyzed the effect of maintenance endocrine therapy (MET) after high-dose chemotherapy with hematopoietic progenitor cell transplant (HDCT) on the progression-free survival (PFS) of patients with hormone-dependent metastatic breast cancer (MBC). One hundred and nine consecutive patients with estrogen receptor (ER) and/or progesterone receptor (PgR)-positive MBC, who were progression free for at least 4 months after HDCT with cyclophosphamide, carmustine and thiotepa (CBT), were analyzed. Of these, 55 were non-randomly submitted to MET. After a median follow-up of 34.4 months (17.1-91.0), univariate analysis showed that MET was significantly associated with improved median PFS (31.1 vs 19.2 months, P = 0.022). Complete response to HDCT, pattern of metastatic spread, extent of the disease, single vs multiple metastatic sites, prior endocrine therapy for metastatic disease and prior exposure to any hormonal therapy (adjuvant and/or for the advanced disease) were also associated with PFS at univariate analysis. A multivariate Cox proportional hazard model was fitted to the data in order to correct the effect of MET for the other significant covariates. After correcting for these covariates, MET was still significant, predicting improved PFS (hazard ratio (HR) 0.580, 95% CI; 0.362-0.931). Administration of MET after optimal cytoreduction might result in increased efficacy of HDCT in hormone-dependent metastatic breast cancer.

Adult↗

PubMed1990

Flow-cytometric analysis of colorectal cancer with hepatic metastases and its relationship to metastatic characteristics and prognosis.

Studying the DNA ploidy patterns of 52 primary tumors, diploid tumors accounted for 48.1% and aneuploid tumors for 51.9%. Out of 31 patients with liver metastases, 35.5% had diploid tumors and 64.5%, aneuploid tumors. Heterogeneity (difference in DNA ploidy pattern between the primary lesion and liver metastases) was found in 20% of the patients examined. In 28 of the patients, the liver metastases were unresectable, and their prognoses were such that the 1- and 2-year survival rates from the diploid tumors were 42.9 and 14.3%, respectively, while 1-year survivors from aneuploid tumors died within 2 years. In resected cases of hepatic metastases, the DNA ploidy pattern of the metastatic lesions did not correlate with the metastasis period, extent of spread or number of lesions. The recurrence rate of aneuploid tumors in the residual livers was 50%, which was slightly higher than the rate of 36.4% for diploid tumors. The prognoses in patients with diploid tumors were significantly better than those in patients with aneuploid tumors: 5-year survival was 71.1% in diploid tumor patients, compared with 21% in aneuploid tumor patients.

Colorectal Neoplasms↗

PubMedDate not supplied

GLUT1 immunoreaction patterns reliably distinguish hemangioblastoma from metastatic renal cell carcinoma.

BACKGROUND: Hemangioblastoma and metastatic renal cell carcinoma (RCC) may show striking histologic similarities, and the distinction between these two tumors can be difficult. Both occur in middle age, and both occur with increased incidence in von Hippel-Lindau disease (vHL). GLUT1 is an erythrocyte-type glucose transporter protein that is highly expressed by endothelia in brain--but not most peripheral--microvasculature, and by tumor cells in many epithelial malignancies. GLUT1 is expressed by endothelial cells in juvenile hemangiomas, and endothelial GLUT1 expression has been reported for 2 hemangioblastomas arising in a single patient with vHL. METHODS: We performed immunoreactions for GLUT1 on archival hemangioblastomas from 12 patients (one with vHL), and on RCCs metastatic to brain of 9 patients. RESULTS: Hemangioblastomas showed intense endothelial GLUT1 reactivity in 11/12 tumors resections; the only GLUT1-negative tumor was one for which only previously frozen material was available for immunoreaction, and this tissue showed poor GLUT1 immunoreactivity of internal erythrocyte controls. Hemangioblastoma stromal cell reactivity was found in only 1 case, and was weak and focal. RCCs, in contrast, showed no intralesional endothelial GLUT1 reactivity, but did show intense tumor cell membrane reactivity in 9/9 cases. CONCLUSION: that GLUT1 immunoreactivity patterns reliably distinguish hemangioblastoma from RCC.

Adult↗

PubMed2006

Preparing the "soil": the premetastatic niche.

Current focus on cancer metastasis has centered on the intrinsic factors regulating the cell autonomous homing of the tumor cells to the metastatic site. Specific up-regulation of fibronectin and clustering of bone marrow-derived cellular infiltrates coexpressing matrix metalloproteinases in distant tissue sites before tumor cell arrival are proving to be indispensable for the initial stages of metastasis. These bone marrow-derived hematopoietic progenitors that express vascular endothelial growth factor receptor 1 mobilize in response to the unique array of growth factors produced by the primary tumor. Their arrival in distant sites represents early changes in the local microenvironment, termed the "premetastatic niche," which dictate the pattern of metastatic spread. Focus on the early cellular and molecular events in cancer dissemination and selectivity will likely lead to new approaches to detect and prevent metastasis at its earliest inception.

Bone Marrow Cells↗

PubMed1984

Flow-cytometric analysis of DNA content in postmortem tissue.

In order to determine the heterogeneity of ploidy in disseminated cancer, we assessed the suitability of postmortem tissue for flow-cytometric analysis of cellular DNA content. Forty tissue samples from various tumor-bearing sites in 12 patients with widely metastatic cancer were analyzed. In eight cases studied there was a single unimodal ploidy level in all disease sites studied. The remaining four cases revealed bimodal tumor populations present in different proportions in the various sites studied. No difference in ploidy could be detected between irradiated and nonirradiated sites in patients who had received radiation therapy. Samples taken from normal tissues all revealed diploid DNA content, suggesting that DNA fluorescence is not altered in the immediate postmortem period. Systematic analysis of cellular DNA content in autopsy material is feasible and may contribute to our understanding of patterns of metastatic spread in patients with cancer.

Autopsy↗

PubMed1995

Frequent incidence of extrapulmonary sites of initial metastasis in patients with liposarcoma.

BACKGROUND: The vast majority of soft tissue sarcomas spread initially to the lungs and then to other sites. The lung has been the most carefully monitored organ system during routine surveillance for a metastasis. Liposarcoma is one of the most common soft tissue sarcomas and has been noted to have extrapulmonary sites of initial metastasis. This study was undertaken to investigate both the frequency and distinguishing features of initial extrapulmonary metastasis in patients with liposarcoma. METHODS: A review of 60 patients with liposarcoma treated at the Massachusetts General Hospital (MGH) from 1971 to 1990 was performed. Survival and regression analyses were used to analyze disease free intervals and prognostic factors. RESULTS: Metastatic disease occurred in 37% of patients and local failure in 17%. Among the subset of patients who underwent primary definitive surgery at the MGH, the incidence of local failure was 3%. An unusually high incidence of extrapulmonary site of first metastasis was found. Isolated extrapulmonary disease was the site of initial metastasis in 59% of patients. In contrast to patients with an initial pulmonary metastasis, patients with an initial extrapulmonary metastasis had a statistically significant (P = 0.001) longer disease free interval from diagnosis to first metastasis. CONCLUSIONS: Liposarcoma, in comparison with other soft tissue sarcomas, has a different pattern of metastatic spread, with a tendency toward extrapulmonary sites. In addition, patients with extrapulmonary metastases have a longer disease free interval compared with patients with pulmonary metastasis.

Adolescent↗

PubMed1989

Spontaneously metastasizing rat sarcomas LW13K2 and RPS: assessment by the immunogenetic test of malignancy, in vitro behaviour and karyology.

Populations of LW13K2 sarcoma derivatives were compared for their malignancy, patterns of cell behaviour in vitro (dynamic morphology and migration) and karyological pattern. The following tumour cell populations were used: the original LW13K2 sarcoma from inbred LEW/CUB rats, RPS sarcoma derived from it by neoplastic progression, four cell populations isolated in vitro from metastases of a syngeneic LEW-CUB strain rat with RPS tumour and four neoplastic cell populations isolated from spontaneous metastases shed by RPS sarcoma in allogeneic rats, differing from LEW/CUB in weak alloantigenic loci. Although RPS tumour did not grow progressively in MHC-different recipients (while the original LW13K2 tumour did), it grew progressively and metastasized in all groups of non-MHC allogeneic recipients. Parallel with the metastatic potential patterns of in vitro behaviour, such as an increased incidence of the quasi-stellate morphotype at slightly acid culture conditions endowed with enhanced changeability of the cell shape and migrational activity, were found. Cytogenetic analysis demonstrated rather stable chromosomal patterns over the cascade of neoplastic progression from LW13K2 sarcoma over RPS sarcoma to freshly isolated metastases. This indicated that the apparent neoplastic progression observed in the cell populations derived from LW13K2 sarcoma is with high probability not due to the selection at the chromosomal level.

Animals↗

PubMed2002

E-cadherin expression in the primary tumors and metastatic lymph nodes of poorly differentiated types of rectal cancer.

PURPOSE: Dysfunction of E-cadherin, a cell-cell adhesion molecule, correlates with the grade of dedifferentiation and/or invasiveness of rectal cancer. However, the relationship between E-cadherin expression in the primary tumor and the potential for metastasis has never been reported. METHODS: E-cadherin expression in 43 primary rectal cancer, including 10 poorly differentiated type, and their associated metastatic lymph nodes (LN mets.) were immunohistochemically evaluated. RESULTS: Heterogeneous immunostaining, suggestive of damage to the E-cadherin-mediated cell-cell adhesion system, was seen in 13 of the 28 LN mets positive primary lesions, but in 0 of the 15 LN mets negative primaries. Furthermore, the incidence of heterogeneous immunostaining differed significantly between poorly differentiated and differentiated cancers, being seen in 8 of 10 cases and 5 of 33 cases, respectively (P = 0.0003 by Fisher's exact test). Interestingly, most of the LN mets. foci (25 of 28 cases) showed homogeneous staining regardless of the E-cadherin staining pattern of the primary lesion. CONCLUSION: Heterogeneous immunostaining of E-cadherin in poorly differentiated rectal cancer was associated with lymph node metastasis. Its staining pattern in metastatic lymph nodes were, however, generally homogenous.

Adenocarcinoma↗

PubMed1995

[Analysis of DNA content in primary colorectal carcinoma and lung metastasis].

We analyzed DNA content of resected primary colorectal carcinoma and lung metastasis by flow cytometry. Of the 14 primary lesions, 5 cases showed diploid pattern, 9 cases aneuploid pattern. In contrast, 12 metastatic lung lesions of 19 showed diploid pattern and 7 lesions aneuploid pattern. DNA index of primary and metastatic lesions was 1.4 +/- 0.4 and 1.2 +/- 0.2, respectively (p = 0.08). In combination of DNA ploidy pattern between primary and metastatic lesions, there were 11 in which ploidy pattern was identical, 1 in which metastasis was aneuploid and primary was diploid, 7 in which metastasis was diploid and primary was aneuploid. Four year, survival rate from operation of metastasis was better in diploid pattern than in aneuploid pattern, but it was not significant. These results indicate that patients who have operative indication of metastasis from colorectal carcinoma have metastatic tumor which shows relatively good biological behavior (diploid tumors) and that there are heterogeneity of ploidy pattern between primary and metastatic lesions.

Adult↗

PubMed1990

Neoplasms metastatic to the heart: review of 3314 consecutive autopsies.

Cardiac involvement by metastatic neoplasms is relatively uncommon and usually occurs with widely disseminated disease. Ninety-five cases with cardiac metastases from autopsies performed over a 14-year period (1974-1987) at Loyola University Medical Center are reviewed. During this period, 3314 autopsies were performed with an average annual autopsy rate of 35%. In 806 (24.3%), a malignant disease was found, and in 95 (11.8%), there was cardiac involvement by tumor. The most common malignancies encountered in order of decreasing frequency were lung, lymphoma, breast, leukemia, stomach, melanoma, liver, and colon. Although the percentage of cardiac metastasis compares favorably with previous reports in the literature, an identical rate was present during both halves of the 14-year period studied. Improved diagnostic capabilities and treatment protocols in recent years have apparently not significantly affected the incidence, distribution, or patterns of metastatic spread to the heart.

Breast Neoplasms↗

PubMed2004

Metastatic potentiality of micropapillary and conventional histological patterns: a comparative study of 82 pulmonary adenocarcinomas.

BACKGROUND: The recently described micropapillary pattern (MPP) is potentially a strong unfavorable prognostic marker for adenocarcinoma of the lung. None of the previous studies compared the association to nodal metastasis between conventional histological patterns and MPP. METHOD: Histological patterns (1=solid, 2=poorly formed acinar 3=well formed acinar, 4=papillary, 5=bronchioloalveolar), and MPP were semiquantitatively evaluated in 82 pulmonary adenocarcinomas and correlated with nodal status. RESULTS: Mean percentages of pattern 1 and 2 are higher in node positive (N+) group (33.9% vs 19.3%, p=0.046; and 20.8% vs 13.4%, p=0.19, respectively). Analysis of the combined amount of pattern 1 and 2 revealed increased statistical significance (54.6% vs 32.5%, p=0.007). Mean percentages of pattern 3, 4 and 5 tended to be lower in N+ group (22.8% vs 29.4%, p=0.24; 2.8% vs 6.2%, p=0.33; and 17.9% vs 31.2%, p=0.053, respectively). Analysis of the combined amount of pattern 3, 4 and 5 showed increased statistical significance (43.3% vs 66.8%, p=0.005). Mean percentage of MPP was higher in N+ group (28.3% vs 11.3%, p=0.0007) after excluding the cases with more than 80% percent of pattern 1 and 2. The criterion of MPP > or = 20% or combined pattern 1 and 2 > 50% of tumor is strongly associated with nodal metastasis (p=0.0015). Pattern 1 has the highest rate of correspondence of having a similar pattern in metastases (18/26, 69.2%), followed by MPP (10/19, 52.6%), and pattern 2 (12/23, 52.2%). CONCLUSION: MPP has comparable metastatic impact to the solid and the poorly formed acinar patterns and it is prognostically informative to document the presence or absence of the solid plus poorly formed glandular pattern > 50% and MPP > or = 20% when histological subtype is evaluated.

Adenocarcinoma↗