Editing Metastasis (section)

==Diagnosis==
[[File:Pulmonary metastases shown on Chest X-Ray .jpg|thumb|Pulmonary metastases shown on Chest X-Ray]]
The cells in a metastatic tumor resemble those in the primary tumor. Once the cancerous tissue is examined under a microscope to determine the cell type, a doctor can usually tell whether that type of cell is normally found in the part of the body from which the tissue sample was taken.{{citation needed|date=September 2024}}

For instance, [[breast cancer]] cells look the same whether they are found in the breast or have spread to another part of the body. So, if a tissue sample taken from a tumor in the lung contains cells that look like breast cells, the doctor determines that the lung tumor is a secondary tumor. Still, the determination of the primary tumor can often be very difficult, and the pathologist may have to use several adjuvant techniques, such as [[immunohistochemistry]], FISH ([[fluorescent in situ hybridization]]), and others. Despite the use of techniques, in some cases the primary tumor remains unidentified.

Metastatic cancers may be found at the same time as the primary tumor, or months or years later. When a second tumor is found in a patient that has been treated for cancer in the past, it is more often a metastasis than another primary tumor.

It was previously thought that most cancer cells have a low metastatic potential and that there are rare cells that develop the ability to metastasize through the development of somatic mutations.<ref>{{Cite journal |vauthors=Poste G, Fidler IJ |date=January 1980 |title=The pathogenesis of cancer metastasis |journal=Nature |volume=283 |issue=5743 |pages=139–146 |bibcode=1980Natur.283..139P |citeseerx=10.1.1.553.5472 |doi=10.1038/283139a0 |pmid=6985715 |s2cid=4302076}}</ref>  According to this theory, diagnosis of metastatic cancers is only possible after the event of metastasis.  Traditional means of diagnosing cancer (e.g. a [[biopsy]]) would only investigate a subpopulation of the cancer cells and would very likely not sample from the subpopulation with metastatic potential.<ref name="signature">{{Cite journal |vauthors=Ramaswamy S, Ross KN, Lander ES, Golub TR |date=January 2003 |title=A molecular signature of metastasis in primary solid tumors |journal=Nature Genetics |volume=33 |issue=1 |pages=49–54 |doi=10.1038/ng1060 |pmid=12469122 |s2cid=12059602}}</ref>

The [[Somatic (biology)|somatic]] mutation theory of metastasis development has not been substantiated in human cancers.  Rather, it seems that the genetic state of the primary tumor reflects the ability of that cancer to metastasize.<ref name="signature" />  Research comparing gene expression between primary and metastatic [[adenocarcinomas]] identified a subset of genes whose expression could distinguish primary tumors from metastatic tumors, dubbed a "metastatic signature."<ref name="signature" />  Up-regulated genes in the signature include:  [[SNRPF]], [[HNRPAB]], [[DHPS]] and [[securin]].  [[Actin]], [[myosin]] and [[MHC class II]] down-regulation was also associated with the signature.  Additionally, the metastatic-associated expression of these genes was also observed in some primary tumors, indicating that cells with the potential to metastasize could be identified concurrently with diagnosis of the primary tumor.<ref>{{Cite journal |author-link=Laura J. van't Veer |vauthors=van 't Veer LJ, Dai H, van de Vijver MJ, He YD, Hart AA, Mao M, Peterse HL, van der Kooy K, Marton MJ, Witteveen AT, Schreiber GJ, Kerkhoven RM, Roberts C, Linsley PS, Bernards R, Friend SH |date=January 2002 |title=Gene expression profiling predicts clinical outcome of breast cancer |journal=Nature |volume=415 |issue=6871 |pages=530–536 |doi=10.1038/415530a |pmid=11823860 |s2cid=4369266 |hdl-access=free |hdl=1874/15552}}</ref> Recent work identified a form of genetic instability in cancer called [[chromosome instability]] (CIN) as a driver of metastasis.<ref>{{Cite journal |vauthors=Bakhoum SF, Ngo B, Laughney AM, Cavallo JA, Murphy CJ, Ly P, Shah P, Sriram RK, Watkins TB, Taunk NK, Duran M, Pauli C, Shaw C, Chadalavada K, Rajasekhar VK, Genovese G, Venkatesan S, Birkbak NJ, McGranahan N, Lundquist M, LaPlant Q, Healey JH, Elemento O, Chung CH, Lee NY, Imielenski M, Nanjangud G, Pe'er D, Cleveland DW, Powell SN, Lammerding J, Swanton C, Cantley LC |date=January 2018 |title=Chromosomal instability drives metastasis through a cytosolic DNA response |journal=Nature |volume=553 |issue=7689 |pages=467–472 |bibcode=2018Natur.553..467B |doi=10.1038/nature25432 |pmc=5785464 |pmid=29342134}}</ref> In aggressive cancer cells, loose DNA fragments from unstable chromosomes spill in the cytosol leading to the chronic activation of innate immune pathways, which are hijacked by cancer cells to spread to distant organs.

Expression of this metastatic signature has been correlated with a poor prognosis and has been shown to be consistent in several types of cancer.  Prognosis was shown to be worse for individuals whose primary tumors expressed the metastatic signature.<ref name="signature" />  Additionally, the expression of these metastatic-associated genes was shown to apply to other cancer types in addition to [[adenocarcinoma]].  Metastases of [[breast cancer]], [[medulloblastoma]] and [[prostate cancer]] all had similar expression patterns of these metastasis-associated genes.<ref name="signature" />

The identification of this metastasis-associated signature provides promise for identifying cells with metastatic potential within the primary tumor and hope for improving the prognosis of these metastatic-associated cancers.  Additionally, identifying the genes whose expression is changed in metastasis offers potential targets to inhibit metastasis.<ref name="signature" />

<gallery>
File:Bone metastasis.jpg|Cut surface of a [[humerus]] sawn lengthwise, showing a large [[cancer]]ous metastasis (the whitish tumor between the head and the shaft of the bone)
File:Lymph node with papillary thyroid carcinoma.jpg|[[Micrograph]] of thyroid cancer ([[papillary thyroid carcinoma]]) in a [[lymph node]] of the neck. [[H&E stain]]
File:MultipleLiverMets2008.jpg|[[Ct scan|CT image]]  of multiple liver metastases
File:LungMets2008.jpg|[[Ct scan|CT image]] of a lung metastasis
File:Adenocarcinoma liver metastasis.jpg|Metastasis proven by [[liver]] [[biopsy]] (tumor ([[adenocarcinoma]])—lower two-thirds of image). [[H&E stain]].
File:MetsToLungs.png|Metastatic cancer in the lungs
File:MetstoBrain(LungPri)Mark.png|Metastases from the lungs to the brain
File:Metstopancrease.png|Metastases from the lungs to the pancreas
</gallery>