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PubMed1993

Expression of annexins on the surfaces of non-metastatic and metastatic human and rodent tumor cells.

Annexins are a large group of calcium-dependent cytoskeletal- and membrane-associated proteins whose properties include cytoskeleton and phospholipid binding and mitotic signal transduction. Although annexin-like molecules have been reported on the external plasma membranes of certain cells, in general they are considered to be cytoplasmic proteins. We report here the heterogenous expression of certain annexins (I-VI) on the external cell surfaces of non-metastatic and metastatic murine (RAW117 large-cell lymphoma), rat (13762NF mammary adenocarcinoma) and some human (KM12 and HT29 colorectal carcinoma) cell lines but not on some other cell lines such as human (A375 and MeWo) and mouse (B16) melanoma. The implication of annexin cell surface expression in the metastatic process is discussed with respect to tumor cell adhesion.

Animals↗
PubMed1998

Renal Cell Carcinoma Metastatic to the Thyroid Gland: A Comparative Molecular Study Between the Primary and the Metastatic Tumor.

A case of renal cell carcinoma metastatic to the thyroid gland is presented. The thyroid tumor showed typical features: clear cells arranged in nests with a prominent sinusoidal vascular pattern. The histologic appearance was identical to the renal tumor removed 6 yr before. A comparative molecular study between the primary and the metastatic tumor showed a common profile with a loss of heterozygosity at identical loci on chromosome 3, which provided further support to the metastatic nature of the thyroid tumor. However, the frequent existence of allele losses on chromosome 3p in both renal cell carcinomas and primary thyroid follicular carcinomas rest some force from such a molecular approach to the differential diagnosis of thyroid tumors that contain a predominant population of clear cells.

Journal Article↗
PubMed2006

Continued survival of more than ten years, without resection of metastatic disease, in patients with metastatic colorectal cancer treated with biomodulated fluorouracil: report of two cases.

The treatment of metastatic colorectal cancer by chemotherapy alone was considered palliative and without the potential to cure patients unless patients were rendered resectable. We report two patients with metastatic colorectal cancer involving the liver who were considered inoperable and were treated with systemic chemotherapy using biomodulated 5-fluorouracil. Both patients received 5-fluorouracil and N-(phosphonoacetyl)-l-aspartic acid; one also received methotrexate, leucovorin, and triacetyluridine with the N-(phosphonoacetyl)-l-aspartic acid and 5-fluorouracil. Both patients had a complete remission with chemotherapy and are still alive with no evidence of cancer ten years after the diagnosis of unresectable metastatic disease. These patients provide evidence that prolonged survival can be achieved withsystemic chemotherapy without the use of surgery or other forms of local therapy. These patients also confirm the importance of continued investigation of fluorouracil modulating agents, which may further enhance the recent progress made with fluorouracil-based combination chemotherapy for colorectal cancer.

Acetates↗
PubMed1986

Characterization of cellular and extracellular plasma membrane vesicles from a low metastatic lymphoma (Eb) and its high metastatic variant (ESb): inhibitory capacity in cell-cell interaction systems.

Spontaneously shed extracellular plasma membrane vesicles (ECM) of a highly metastatic murine tumor line (ESb) were compared with plasma membrane vesicles (PM) of the same cells prepared by the nitrogen cavitation method and with ECM and PM preparations of the related low metastatic tumor line Eb. From a previous biochemical analysis it was concluded that the exfoliation of ECM vesicles, which is very pronounced in metastatic ESb cells, is not a random process. This conclusion is further corroborated by the present functional analysis. Compared to ESb PM, ESb-derived ECM were selectively enriched for Fc receptors and depleted in glycoproteins with affinity for hepatocytes. Tumor-derived ECM carried the same tumor antigen as the corresponding tumor line and showed in comparison to PM material an increased inhibitor capacity in a T-cell-mediated tumor-specific cytotoxicity test.

Animals↗
PubMed2000

The role of cytokeratins 20 and 7 and estrogen receptor analysis in separation of metastatic lobular carcinoma of the breast and metastatic signet ring cell carcinoma of the gastrointestinal tract.

Metastatic signet ring cell carcinomas of unknown primary site can represent a clinical problem. Gastrointestinal signet ring cell carcinomas and invasive lobular carcinomas of the breast are the most common sources of these metastases. Immunohistochemical algorithms have been successfully used in the search for the unknown primary adenocarcinomas. In the present study a series of primary invasive lobular breast carcinomas (79 cases) and their metastases and a series of gastrointestinal signet ring cell carcinomas (22 primary and 13 metastases) were stained with monoclonal antibodies for cytokeratin (CK) 20 and CK7 and for estrogen receptors (ER). The staining was evaluated as negative (no staining), focally (less than 10% of the tumor cells stained) or diffusely positive. All the primary and metastatic gastrointestinal signet ring cell carcinomas proved to be CK20 positive, while only 2/79 (3%) of the primary and 1/21 metastatic lobular carcinomas (5%) stained positively for this CK. None of the gastrointestinal carcinomas and the majority of the lobular carcinomas expressed ER. The majority of the tumors were CK7+. Using CK20 alone, 33 of 34 metastases could be properly classified as gastrointestinal (CK20+) or mammary (CK20-). ER identified 31/34 of breast cancer metastases. By combining the results of CK20 and ER staining all the metastases could be properly classified as the CK20+/ER- pattern identified all the gastrointestinal tumors.

Antibodies, Monoclonal↗
PubMed1999

An expanded peripheral T cell population to a cytotoxic T lymphocyte (CTL)-defined, melanocyte-specific antigen in metastatic melanoma patients impacts on generation of peptide-specific CTLs but does not overcome tumor escape from immune surveillance in metastatic lesions.

It is not known if immune response to T cell-defined human histocompatibility leukocyte antigen (HLA) class I-restricted melanoma antigens leads to an expanded peripheral pool of T cells in all patients, affects cytotoxic T lymphocyte (CTL) generation, and correlates with anti-tumor response in metastatic lesions. To this end, a limiting dilution analysis technique was developed that allowed us to evaluate the same frequency of peptide-specific T cells as by staining T cells with HLA-peptide tetrameric complexes. In four out of nine patients, Melan-A/Mart-1(27-35)-specific CTL precursors (CTLp) were >/=1/2,000 peripheral blood lymphocytes and found mostly or only in the CD45RO(+) memory T cell subset. In the remaining five patients, a low (<1/40,000) peptide-specific CTLp frequency was measured, and the precursors were only in the CD45RA(+) naive T cell subset. Evaluation of CTL effector frequency after bulk culture indicated that peptide-specific CTLs could be activated in all patients by using professional antigen-presenting cells as dendritic cells, but CTLp frequency determined the kinetics of generation of specificity and the final number of effectors as evaluated by both limiting dilution analysis and staining with HLA-A*0201-Melan-A/Mart-1 tetrameric complexes. Immunohistochemical analysis of 26 neoplastic lesions from the nine patients indicated absence of tumor regression in most instances, even in patients with an expanded peripheral T cell pool to Melan-A/Mart-1 and whose neoplastic lesions contained a high frequency of tetramer-positive Melan-A/Mart-1-specific T cells. Furthermore, frequent lack of a "brisk" or "nonbrisk" CD3(+)CD8(+) T cell infiltrate or reduced/absent Melan-A/Mart-1 expression in several lesions and lack of HLA class I antigens were found in some instances. Thus, expansion of peripheral immune repertoire to Melan-A/Mart-1 takes place in some metastatic patients and leads to enhanced CTL induction after antigen-presenting cell-mediated selection, but, in most metastatic lesions, it does not overcome tumor escape from immune surveillance.

Adult↗
PubMed2004

The effect of exemestane on serum lipid profile in postmenopausal women with metastatic breast cancer: a companion study to EORTC Trial 10951, 'Randomized phase II study in first line hormonal treatment for metastatic breast cancer with exemestane or tamoxifen in postmenopausal patients'.

BACKGROUND: The impact of aromatase inhibitors (AIs) on non-cancer-related outcomes, which are known to be affected by oestrogens, has become increasingly important in postmenopausal women with hormone-dependent breast cancer. So far, data related to the effect of AIs on lipid profile in postmenopausal women is scarce. This study, as a companion substudy of an EORTC phase II trial (10951), evaluated the impact of exemestane, a steroidal aromatase inactivator, on the lipid profile of postmenopausal metastatic breast cancer (MBC) patients. PATIENTS AND METHODS: The EORTC trial 10951 randomised 122 postmenopausal breast cancer patients to exemestane (E) 25 mg (n = 62) or tamoxifen (T) 20 mg (n = 60) once daily as a first-line treatment in the metastatic setting. Exemestane showed promising results in all the primary efficacy end points of the trial (response rate, clinical benefit rate and response duration), and it was well tolerated with low incidence of serious toxicity. As a secondary end point of this phase II trial, serum triglycerides (TRG), high-density lipoprotein cholesterol (HDL), total cholesterol (TC), lipoprotein a (Lip a), and apolipoproteins (Apo) B and A1 were measured at baseline and while on therapy (at 8, 24 and 48 weeks) to assess the impact of exemestane and tamoxifen on serum lipid profiles. Of the 122 randomised patients, those who had baseline and at least one other lipid assessment are included in the present analysis. The patients who received concomitant drugs that could affect lipid profile are included only if these drugs were administered throughout the study treatment. Increase or decrease in lipid parameters within 20% of baseline were considered as non-significant and thus unchanged. RESULTS: Seventy-two patients (36 in both arms) were included in the statistical analysis. The majority of patients had abnormal TC and normal TRG, HDL, Apo A1, Apo B and Lip a levels at baseline. Neither exemestane nor tamoxifen had adverse effects on TC, HDL, Apo A1, Apo B or Lip a levels at 8, 24 and 48 weeks of treatment. Exemestane and tamoxifen had opposite effects on TRG levels: exemestane lowered while tamoxifen increased TRG levels over time. There were too few patients with normal baseline TC and abnormal TRG, HDL, Apo A1, Apo B and Lip a levels to allow for assessment of E's impact on these subsets. The atherogenic risk determined by Apo A1:Apo B and TC:HDL ratios remained unchanged throughout the treatment period in both the E and T arms. CONCLUSIONS: Overall, exemestane has no detrimental effect on cholesterol levels and the atherogenic indices, which are well-known risk factors for coronary artery disease. In addition, it has a beneficial effect on TRG levels. These data, coupled with E's excellent efficacy and tolerability, support further exploration of its potential in the metastatic, adjuvant and chemopreventive setting.

Adult↗
PubMed1996

Establishment and characterization of new human Burkitt's lymphoma cell lines (HBL-7 and HBL-8) that are highly metastatic in SCID mice: a metastatic SCID mouse model of human lymphoma lines.

Two newly established human Burkitt's lymphoma cell lines (HBL-7 and HBL-8) were characterized by immunophenotypic, cytogenetic and molecular studies. Both cell lines were negative for Epstein-Barr virus (EBV) genome and had chromosomal translocation: t(8;14) (q24;q32). Immunoglobulin (Ig) gene rearrangement analyses confirmed that both cell lines were derived from primary lymphoma cells. These cell lines were heterotransplanted subcutaneously into severe combined immunodeficiency (SCID) mice to investigate the metastatic capacity. The most striking feature of both cell lines was to show highly spontaneous metastasis to distant organs, particularly spleen, bone marrow and ovaries in SCID mice. To elucidate the metastatic factors involved in the process of spontaneous metastasis, cell surface adhesion molecules or extracellular matrix receptors were analyzed. However, the results did not allow a significant correlation between expression levels of those molecules or matrix receptors and spontaneous metastasis in the SCID mouse model. The HBL-7 and HBL-8 cell lines, however, may be a useful tool to elucidate the metastatic mechanisms of human lymphomas in an animal model.

Adolescent↗
PubMedDate not supplied

[Treatment of bone metastatic pain with Sm153-EDTMP. Evaluation of the analgesic response and the existence of differences according to the primary tumor and the metastatic pattern].

AIMS: To evaluate the response to Sm153-EDTMP treatment in patients with metastatic bone pain and the existence of differences in the response according to the scintigraphic pattern (99mTc-MDP) and the primary tumor. MATERIAL AND METHODS: We have evaluated the response to Sm153-EDTMP treatment in 32 patients (17 male and 15 female) who received 38 doses (1 mCi/kg). The primary tumor was prostate cancer in 15 patients, breast in 13, lung in 2, intestinal carcinoid in one and unknown in one. Two types of response were considered: a) effective and b) non-effective. Patients were classified into 3 groups according to the metastatic pattern: 1) Superscan (SS), 2) Generalized metastases (GM) and 3) Regional metastases (RM). RESULTS: There was effective response in 24 doses (63.15%) and non-effective in 14 (36.84%). The mean duration of the response was 12.08 weeks. Patients with GM pattern showed 16 effective responses (76.19%) and 5 non-effective (23.8%). In SS pattern there were 6 effective responses (60%) and 4 non-effective (40%) and 2 effective (28.57%) and 5 non-effective (71.53%) in RM pattern. These differences did not reach statistical significance (p > 0.05). We did not find differences in the response between prostate cancer (12 effective and 6 non-effective) and breast cancer (10 effective and 6 non-effective) (p = 0.79968). CONCLUSIONS: Sm153-EDTMP treatment is efficacious in patients with metastatic bone pain with effective response in 63.15% of the treatments. The response percentage was lower in patients with RM pattern but the differences did not reach statistical significance. There were no differences in the response between prostate and breast cancer patients.

Adult↗
PubMed2000

Gamma knife radiosurgery as a primary treatment for prolactinomas.

OBJECT: The purpose of this study was to estimate the efficacy of gamma knife radiosurgery (GKS) in controlling tumor growth and endocrinopathy associated with prolactinomas. METHODS: Between 1993 and 1997, 164 of 469 patients with pituitary adenomas treated by GKS harbored prolactinomas. The dose to the tumor margin ranged from 9 to 35 Gy (mean 31.2 Gy), and the visual pathways were exposed to a dose of less than 10 Gy. The mean tumor diameter was 13.4 mm. The mean follow-up time for 128 cases was 33.2 months (range 6-72 months). Tumor control was observed in all but two patients who underwent surgery 18 and 36 months, respectively, after GKS. Clinical cure was achieved in 67 cases. Clinical improvement was noted with a decrease in the hyperprolactinemia after GKS. Nonetheless, in 31 (29%) of 108 patients who were followed for more than 2 years no improvement in serum prolactin levels was demonstrated, although this could be normalized by bromocriptine administration after treatment. Nine infertile women became pregnant 2 to 13 months after GKS and all gave birth to normal children. There was no visual deterioration related to GKS. Five women experienced premature menopause. In these patients there was subtotal disappearance of the tumor and an empty sella developed. CONCLUSIONS: Gamma knife radiosurgery as a primary treatment for prolactinomas can be safe and effective both for controlling tumor growth and for normalization of prolactin hypersecretion. A higher margin dose (> or = 30 Gy) seemed to be associated with a better clinical outcome. Gamma knife radiosurgery may make prolactinomas more sensitive to the bromocriptine.

Humans↗
PubMed1999

Study of angiogenesis induced by metastatic and non-metastatic liver cancer by corneal micropocket model in nude mice.

AIM:To study the angiogenesis induced by liver cancer with different metastatic potentials using corneal micropocket model in nude mice.METHODS: Corneal micropockets were created in nude mice. Tumor tissues and liver tissues were implanted into the corneal micropockets. Angiogenesis was observed usinga digital camera under slit-lamp biomicroscope,and compared among different grafts and incision alone. Vascular responses were recorded in regard to the range, number and length of new blood vessels toward the grafts or incisions.RESULTS:Vascular responses induced by tumor tissues were greater than those by incision alone and liver tissue grafts. LCI-D20 induced more intensive angiogenesis than LCI-D35.CONCLUSION:Highly metastatic liver cancer LCI D20 was more angiogenic than low metastatic cancer LCI D35 and liver tissue. Micropocket was a useful model to study dynamic process of angiogenesis in vivo.

Journal Article↗
PubMed2001

Establishment of cell clones with different metastatic potential from the metastatic hepatocellular carcinoma cell line MHCC97.

AIM: To establish clone cells with different metastatic potential for the study of metastasis-related mechanisms. METHODS: Cloning procedure was performed on parental hepatocellular carcinoma (HCC) cell line MHCC97, and biological characteristics of the target clones selected by in vivo screening were studied. RESULTS: Two clones with high (MHCC97-H) and low (MHCC97-L) metastatic potential were isolated from the parent cell line. Compared with MHCC97-L, MHCC97-H had smaller cell size (average cell diameter 43 microm vs 50 microm) and faster in vitro and in vivo growth rate (tumor cell doubling time was 34.2h vs 60.0h). The main ranges of chromosomes were 55-58 in MHCC97-H and 57-62 in MHCC97-L. Boyden chamber in vitro invasion assay demonstrated that the number of penetrating cells through the artificial basement membrane was (37.5 +/- 11.0) cells/field for MHCC97-H vs (17.7 +/- 6.3)/field for MHCC97-L. The proportions of cells in G0-G1 phase, S phase, and G2-M phase for MHCC97-H/MHCC97-L were 0.56/0.65, 0.28/0.25 and 0.16/0.10, respectively, as measured by flow cytometry. The serum AFP levels in nude mice 5wk after orthotopic implantation of tumor tissue were (246 +/- 66) microg.L(-1) for MHCC97-H and (91 +/- 66) microg.L(-1) for MHCC97-L. The pulmonary metastatic rate was 100% (10/10) vs 40% (4/10). CONCLUSION: Two clones of the same genetic background but with different biological behaviors were established, which could be valuable models for investigation on HCC metastasis.

Albumins↗
PubMedDate not supplied

Expression of laminin in metastatic melanoma cell lines with different metastatic potential.

Cancer metastasis is a complex multi-step process in which tumor cells leave the primary site and develop a secondary tumor in distant organs. Laminin plays an important role in this process. The expression of laminin in four melanoma cell lines with different metastatic potentials was investigated by immunohistochemistry, immunogold electron microscopy and Western blotting. Our results showed that the expression of endogenous laminin and the percentage of the positive cells are higher with increased metastatic potentials. It is, thus, suggested that endogenous laminin may contribute to the different metastatic properties in the melanoma cell line.

Blotting, Western↗
PubMedDate not supplied

Identification of metastasis-associated genes by transcriptional profiling of a pair of metastatic versus non-metastatic human mammary carcinoma cell lines.

Cell lines 4A4 and 2C5 are the respective metastatic and non-metastatic variants of the human mammary carcinoma cell line MDA-MB-435 in the nude mouse system. We compared the transcriptional profile of approximately 5000 full-length genies using the Affymetrix HuGene FL Array technology. We have shown that the metastatic phenotype is mediated by different functional categories of genes, e.g. genes involved in immune response, genes responsible for tumor antigens, genes involved in migration and invasion, genes involved in mediating signal transduction, genes responsible for transcription factors, genes involved in phospholipid signaling, genes involved in modulation of extracellular matrix and cytoskeleton, genes with a cell-type specific mode of expression and genes which do not fit into the subclasses as defined above. Our results suggest an important role of Autocrine Motility Factor (AMF) as a mediator of metastasis in this system.

Animals↗
PubMed2002

Current status of interleukin-2 therapy for metastatic renal cell carcinoma and metastatic melanoma.

Interleukin-2 (IL-2, Proleukin) is one of the most effective agents in the treatment of metastatic renal cell carcinoma and metastatic melanoma. High-dose IL-2 therapy produces overall response rates of 15% to 20%; however, it is associated with significant toxicities that affect essentially every organ system. Although IL-2-related toxicities are usually reversible with therapy discontinuation, alternative IL-2 regimens have been evaluated. Several phase II studies have demonstrated that administering lower doses of IL-2 by IV bolus or continuous IV infusion or subcutaneously produces overall response rates similar to those with high-dose IL-2 therapy; however, randomized clinical trials have not yet been completed. In renal cell carcinoma, combining IL-2 with interferon alfa (Intron A, Roferon-A) or chemotherapy agents produces similar or increased overall response rates compared with the response rates of IL-2 alone, with no survival advantage. Combination IL-2 regimens in metastatic melanoma patients have produced variable results. The most promising regimens have included various IL-2-based biochemotherapy regimens in other patients. Randomized studies confirming the superiority of these regimens over high-dose IL-2 therapy are needed.

Antineoplastic Agents↗
PubMedDate not supplied

Biomodulation of cancer chemotherapy for metastatic colorectal cancer: a randomized study of weekly low-dose irinotecan alone versus irinotecan plus the oncostatic pineal hormone melatonin in metastatic colorectal cancer patients progressing on 5-fluorouracil-containing combinations.

Recent advances in immunobiological knowledge have suggested the possibility of enhancing the therapeutic activity of various chemotherapeutic agents by a concomitant administration of anti-oxidant drugs and/or immunomodulating neurohormones. In particular, the pineal neurohormone melatonin (MLT), which is able to exert both antioxidant and immunomodulating effects, has been proven to enhance the efficacy of various chemotherapeutic drugs, namely cisplatin, anthracyclines and 5-fluorouracil, whereas at present there are no data about its possible influence on cytotoxic drugs effective in the treatment of colon cancer other than 5-fluorouracil, such as irinotecan (CPT-11). The present study was performed to evaluate the influence of a concomitant administration of MLT on CPT-11 therapeutic activity in metastatic colorectal cancer. The study included 30 metastatic colorectal cancer patients progressing after at least one previous chemotherapeutic line containing 5-fluorouracil, who were randomized to be treated with CPT-11 alone or CPT-11 plus MLT. According to a weekly low-dose schedule, CPT-11 was given i.v. at 125 mg/m2/week for 9 consecutive weeks. MLT was administered orally at 20 mg/day during the dark period of the day. No complete response was observed. A partial response (PR) was achieved in 2 out of 16 patients treated with CPT-11 alone and in 5 out of 14 patients concomitantly treated with MLT. Moreover, a stable disease (SD) was obtained in 5 out of 16 patients treated with CPT-11 alone and in 7 out of 14 patients treated with CPT-11 plus MLT. Therefore, the percent of disease-control achieved in patients concomitantly treated with MLT was significantly higher than that observed in those treated with chemotherapy alone (12 out of 14 vs 7 out of 16, p < 0.05). The only important toxicity was diarrhoea grade 3-4, which occurred in 6 out of 16 patients treated with CPT-11 alone and in 4 out of 14 patients treated with CPT-11 plus MLT, which required a 50% dose reduction. However, taken together, patients treated with CPT-11 at 50% of the planned dose showed a percent of disease control comparable to that achieved in patients who had no dose reduction (6 out of 10 vs 13 out of 20). This preliminary study shows that the efficacy of weekly low-dose CPT-11 in pretreated metastatic colorectal cancer patients may be enhanced by a concomitant daily administration of the pineal hormone MLT, according to the results previously reported for other chemotherapeutic agents. Moreover, since the dose reduction of CPT-11 does not influence its efficacy, the dose of CPT-11 for successive studies might be not greater than 70 mg/m2.

Adjuvants, Immunologic↗
PubMed2003

Metastatic-associated biological properties and differential gene expression profiles in established highly liver and peritoneal metastatic cell lines of human pancreatic cancer.

To elucidate metastasis mechanisms, we established a Panc-1H5 subline with a highly liver metastatic cell line and a Panc-1P4a with a highly peritoneal metastatic cell line, which were sequentially selected from the parental pancreatic cancer cell line Panc-1. Using these three cell lines, we investigated several biological properties and mRNA levels of differentially-expressed genes involved in cancer metastasis with a cDNA macroarray. The tumorigenicity, motile activity, adhesive activity and cytokine production of metastatic sublines were higher than those of parental Panc-1 cells. Particularly, in Panc-1H5 cells, adhesive activity to the extracellular matrix and angiogenetic factors increased, whereas in Panc-1P4a cells, motile activity was extremely enhanced compared with Panc-1 cells. Histopathological findings for the three cell lines were the same. In cDNA macroarray analysis of Panc-1H5 cells, 11 genes were up-regulated and 20 genes were down-regulated compared with parental Panc-1 cells. In Panc-1P4a cells, 7 genes were up-regulated and 13 genes were down-regulated compared with parental Panc-1 cells. This study provides a demonstration of global gene expression analysis of pancreatic cancer cells with liver and peritoneal metastasis and these results provide new insight into the study of human pancreatic cancer metastasis.

Animals↗
PubMed1988

[Statistical study of metastatic skin cancer--interrelation of the origin of primary tumor, metastatic skin lesions, prognosis and histopathology].

Seventy-five cases of metastatic skin cancers, collected from 15 institutions in West Japan, were included in this study. The most frequently occurring primary tumors were carcinoma of the lung (31%) and carcinoma of the stomach (20%). Metastatic lesions of lung cancer were common on the neck, face and scalp. The anterior part of the abdomen was the most common metastatic site for stomach cancer. The average interval between the appearance of the skin lesion and the detection of the primary cancer was 20 months. Of 23 patients with lung cancer, and of 15 patients with stomach cancer, cutaneous metastasis preceded documentation of the primary tumor in 10 cases of lung cancer and 4 cases of stomach cancer. Three of these 4 cases were signet ring cell carcinoma. The average survival after the development of cutaneous metastasis was 11 months. In 13 cases of lung cancer, it was 4.7 months. The average interval between the appearance of skin lesions and death in 3 patients with squamous cell carcinoma of the lung was 0.8 months.

Aged↗