metastasis
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Introduction
Patterns of metastases of common cancers (see etiology)
Etiology
- metastasis to lymph nodes
- breast cancer(60-80%)
- lung cancer (83% local, 29% distant)
- prostate cancer (68%)
- melanoma (58%)
- ovarian cancer (48% local, 58% distant)
- colorectal carcinoma (53%)
- metastasis to liver
- lung cancer (73%)
- melanoma (63%)
- breast cancer (40-60%)
- ovarian cancer (48%)
- colorectal carcinoma (44%)
- kidney cancer (44%)
- prostate cancer (36%)
- metastasis to lung
- kidney cancer (72%)
- breast cancer (66%)
- melanoma (60%)
- prostate cancer (49%)
- ovarian cancer (34%)
- colorectal carcinoma (16%)
- ipsilateral or contralateral lung cancer (8%)
- thyroid cancer
- head & neck cancer
- metastasis to bone
- prostate cancer (67%)
- breast cancer (62%)
- lung cancer (56%)
- melanoma (48%)
- colorectal carcinoma (27%)
- bladder cancer (26%)
- cervical cancer (21%)
- ovarian cancer (12%)
- kidney cancer (10%)
- metastasis to brain
- lung cancer (37-50%)
- breast cancer (10-23%)
- melanoma (10-48%)
- kidney cancer (19%)
- colorectal carcinoma (11%)
- cervical cancer (9%)
- bladder cancer (7%)
- ovarian cancer (3%)
- prostate cancer (2%)
- metastasis to skin
- melanoma (44%)
- breast cancer (20%)
- colorectal carcinoma (5%)
- bladder cancer (5%)
- kidney cancer (5%)
- ovarian cancer (5%)
- cervical cancer (3%)
- prostate cancer (3%)
- metastasis to adrenal
- melanoma (48%)
- lung cancer (35%)
- bladder cancer (35%)
- colorectal carcinoma (31%)
- breast cancer (31%)
- cervical cancer (31%)
- kidney cancer (20%)
- ovarian cancer (20%)
- prostate cancer (17%)
- metastasis to kidney
- melanoma (27%)
- cervical cancer (26%)
- ipsilateral or contralateral kidney cancer (21%)
- bladder cancer (19%)
- breast cancer (17%)
- lung cancer (16%)
- colorectal carcinoma (13%)
- prostate cancer (11%)
- ovarian cancer (6%)
Pathology
- epithelial-to-mesenchymal transition allows severing of connections to adjacent cells, burrowing through tissue & entering a blood or lymphatic vessel[4]
- relatively few malignant cells shed by primary tumors metastasize successfully
- either the malignant cells do not enter distant organs, or they enter but fail to multiply
- only malignant stem cells may successfully metastasize[3]
- malignant stem cells attach to endothelial cells in the target organ's microcirculation, then invade the stroma
- in the stroma, the malignant stem cells induce fibroblasts to produce periostin (breast cancer metastasis)[3]
- exosomes are released by malignant cells, travel to the distant organs, & prepare it to foster growth of metastatic cells[9][10]
- in the liver exosomes are ingested by Kupffer cells
- exosomes from pancreatic carcinoma cells cause the Kupffer cells to elaborate various factors that foster growth of micrometastases[9]
- exosomes rich in macrophage migration inhibitory factor (MIF) are most likely to foster metastatic growth[9]
- once mesenchymal-like metastatic cells have entered a distant organ, they need to transform themselves back into epithelial-like cells in order to multiply[4]
Genetics
- abnormalities of alpha-catenin are involved in the process of cancer invasion & metastasis
- ROR1 upregulated with metastasis
- upregulation of integrin-linked kinase (ILK) by LIMD2 may play a role in metastasis
Clinical manifestations
- anorexia, unintentional weight loss, lethargy common
- numerous subcutaneous nodules representing skin metastases may occur on some men with lung cancer, colorectal adenocarcinoma & melanoma & some women with breast cancer[12]
Laboratory
- investgational
- cell-sorting to isolate circulating cancer cells from peripheral blood, culture & genotyping[8]
Diagnostic procedures
- biopsy least invasive site first (including peripheral lymph node, i.e. inguinal lymph node)
Management
- early palliative care consult for metastatic cancer
- concurrent chemotherapy & palliative care can increase health-related quality of life & life expectancy 20%[2][11]
- brain metastasis
- a single brain metastasis may be amenable to surgical resection
- multiple brain metastases are treated palliatively
More general terms
More specific terms
- adrenal metastases
- bone metastases
- brain metastases
- carcinomatous meningitis (leptomeningeal metastases)
- drop metastases
- kidney metastases
- Krukenberg's tumor
- liver metastases
- lymph node metastases
- pulmonary metastases
Additional terms
- down-regulated in metastasis protein; small subunit processome component 20 homolog; novel nucleolar protein 73; NNP73; protein key-1A6 (UTP20 DRIM)
- malignant neoplasm (cancer)
- metastasis-associated protein MTA2; metastasis-associated 1-like 1; MTA1-L1 protein; p53 target protein in deacetylase complex (MTA2, MTA1L1, PID)
References
- ↑ Harrison's Principles of Internal Medicine, 14th ed. Fauci et al (eds), McGraw-Hill Inc. NY, 1998, pg 521
- ↑ 2.0 2.1 Medical Knowledge Self Assessment Program (MKSAP) 15, 16, 19. American College of Physicians, Philadelphia 2009, 2012, 2023
- ↑ 3.0 3.1 3.2 Journal Watch Komaroff AL New Insights into the Biology of Metastasis Journal Watch February 1, 2012 Massachusetts Medical Society
Malanchi I et al. Interactions between cancer stem cells and their niche govern metastatic colonization. Nature 2011 Dec 7; 481:85. PMID: https://www.ncbi.nlm.nih.gov/pubmed/22158103
Png KJ et al. A microRNA regulon that mediates endothelial recruitment and metastasis by cancer cells. Nature 2011 Dec 14; 481:190. PMID: https://www.ncbi.nlm.nih.gov/pubmed/22170610 - ↑ 4.0 4.1 4.2 Ocana OH et al Metastatic colonization requires the repression of the epithelial-mesenchymal transition inducer Prrx1. Cancer Cell 2012 Dec 11; 22:709 PMID: https://www.ncbi.nlm.nih.gov/pubmed/23201163
Tsai JH et al. Spatiotemporal regulation of epithelial-mesenchymal transition is essential for squamous cell carcinoma metastasis. Cancer Cell 2012 Dec 11; 22:725. PMID: https://www.ncbi.nlm.nih.gov/pubmed/23201165
van Denderen BJW and Thompson EW. The to and fro of tumour spread. Nature 2013 Jan 24; 493:487. PMID: https://www.ncbi.nlm.nih.gov/pubmed/23344357 - ↑ Cui B, Zhang S, Chen L et al Targeting ROR1 Inhibits Epithelial-Mesenchymal Transition and Metastasis. Cancer Res. 2013 Jun 15;73(12):3649-60 PMID: https://www.ncbi.nlm.nih.gov/pubmed/23771907
- ↑ Khasraw M, Posner JB. Neurological complications of systemic cancer. Lancet Neurol. 2010 Dec;9(12):1214-27 PMID: https://www.ncbi.nlm.nih.gov/pubmed/21087743
- ↑ Peng H et al LIMD2 Is a Small LIM-Only Protein Overexpressed in Metastatic Lesions That Regulates Cell Motility and Tumor Progression by Directly Binding to and Activating the Integrin-Linked Kinase. Cancer Res March 1, 2014 74; 1390 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/24590809 <Internet> http://cancerres.aacrjournals.org/content/74/5/1390.abstract
- ↑ 8.0 8.1 Yu M, Bardia A, Aceto N et al Cancer therapy. Ex vivo culture of circulating breast tumor cells for individualized testing of drug susceptibility. PMID: https://www.ncbi.nlm.nih.gov/pubmed/25013076
- ↑ 9.0 9.1 9.2 9.3 Komaroff AL New Hypothesis on What Allows Metastatic Deposits to Grow. NEJM Journal Watch. May 28, 2015 Massachusetts Medical Society (subscription needed) http://www.jwatch.org
Costa-Silva B et al. Pancreatic cancer exosomes initiate pre-metastatic niche formation in the liver. Nat Cell Biol 2015 May 18 PMID: https://www.ncbi.nlm.nih.gov/pubmed/25985394 - ↑ 10.0 10.1 Hoshino A et al. Tumour exosome integrins determine organotropic metastasis. Nature 2015 Nov 19; 527:329. PMID: https://www.ncbi.nlm.nih.gov/pubmed/26524530
Rak J. Cancer.Organ-seeking vesicles. Nature 2015 Nov 19; 527:312 PMID: https://www.ncbi.nlm.nih.gov/pubmed/26524529 - ↑ 11.0 11.1 Geriatric Review Syllabus, 11th edition (GRS11) Harper GM, Lyons WL, Potter JF (eds) American Geriatrics Society, 2022
- ↑ 12.0 12.1 NEJM Knowledge+ Dermatology
- ↑ National Cancer Institute (NCI) Metastatic Cancer https://www.cancer.gov/types/metastatic-cancer