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metastasis

Patterns of metastases of common cancers (see etiology) Etiology: 1) 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%) 2) metastasis to liver - lung cancer (73%) - melanoma (63%) - breast cancer (40-60%) - ovarian cancer (48%) - colorectal carcinoma (44%) - kidney cancer (44%) - prostate cancer (36%) 3) 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 4) 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%) 5) 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%) 6) 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%) 7) 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%) 8) 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] Special laboratory: - 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

Interactions

disease interactions

Related

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)

Specific

adrenal metastases bone metastases brain metastases carcinomatous meningitis (leptomeningeal metastases) drop metastases kidney metastases Krukenberg's tumor liver metastases lymph node metastases pulmonary metastases

General

neoplastic process secondary malignant neoplasm

References

  1. Harrison's Principles of Internal Medicine, 14th ed. Fauci et al (eds), McGraw-Hill Inc. NY, 1998, pg 521
  2. Medical Knowledge Self Assessment Program (MKSAP) 15, 16, 19. American College of Physicians, Philadelphia 2009, 2012, 2023
  3. 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: 22158103 - Png KJ et al. A microRNA regulon that mediates endothelial recruitment and metastasis by cancer cells. Nature 2011 Dec 14; 481:190. PMID: 22170610
  4. Ocana OH et al Metastatic colonization requires the repression of the epithelial-mesenchymal transition inducer Prrx1. Cancer Cell 2012 Dec 11; 22:709 PMID: 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: 23201165 - van Denderen BJW and Thompson EW. The to and fro of tumour spread. Nature 2013 Jan 24; 493:487. PMID: 23344357
  5. 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: 23771907
  6. Khasraw M, Posner JB. Neurological complications of systemic cancer. Lancet Neurol. 2010 Dec;9(12):1214-27 PMID: 21087743
  7. 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 PMID: 24590809 http://cancerres.aacrjournals.org/content/74/5/1390.abstract
  8. 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: 25013076
  9. 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: 25985394
  10. Hoshino A et al. Tumour exosome integrins determine organotropic metastasis. Nature 2015 Nov 19; 527:329. PMID: 26524530 - Rak J. Cancer.Organ-seeking vesicles. Nature 2015 Nov 19; 527:312 PMID: 26524529
  11. Geriatric Review Syllabus, 11th edition (GRS11) Harper GM, Lyons WL, Potter JF (eds) American Geriatrics Society, 2022
  12. NEJM Knowledge+ Dermatology
  13. National Cancer Institute (NCI) Metastatic Cancer https://www.cancer.gov/types/metastatic-cancer