Difference between revisions of "Lung carcinoma with ALK rearrangement"

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Lung carcinoma with ALK rearrangement (view source)

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[[Image:ALK positive lung adenocarcinoma -- low mag.jpg|thumb|right|[[Micrograph]] showing ALK positive lung adenocarcinoma. [[H&E stain]].]]
'''Lung carcinoma with ALK rearrangement''' is subset of [[lung adenocarcinoma]].
'''Lung carcinoma with ALK rearrangement''' is subset of [[lung adenocarcinoma]].


==General==
==General==
ALK (Anaplastic lymphoma receptor tyrosine kinase)
ALK (anaplastic lymphoma (receptor tyrosine) kinase):
*Approximately 1-5% non-small cell lung carcinoma.<ref name=pmid21753699>{{Cite journal  | last1 = Yoshida | first1 = A. | last2 = Tsuta | first2 = K. | last3 = Nakamura | first3 = H. | last4 = Kohno | first4 = T. | last5 = Takahashi | first5 = F. | last6 = Asamura | first6 = H. | last7 = Sekine | first7 = I. | last8 = Fukayama | first8 = M. | last9 = Shibata | first9 = T. | title = Comprehensive histologic analysis of ALK-rearranged lung carcinomas. | journal = Am J Surg Pathol | volume = 35 | issue = 8 | pages = 1226-34 | month = Aug | year = 2011 | doi = 10.1097/PAS.0b013e3182233e06 | PMID = 21753699 }}</ref>
*Approximately 1-5% non-small cell lung carcinoma.<ref name=pmid21753699>{{Cite journal  | last1 = Yoshida | first1 = A. | last2 = Tsuta | first2 = K. | last3 = Nakamura | first3 = H. | last4 = Kohno | first4 = T. | last5 = Takahashi | first5 = F. | last6 = Asamura | first6 = H. | last7 = Sekine | first7 = I. | last8 = Fukayama | first8 = M. | last9 = Shibata | first9 = T. | title = Comprehensive histologic analysis of ALK-rearranged lung carcinomas. | journal = Am J Surg Pathol | volume = 35 | issue = 8 | pages = 1226-34 | month = Aug | year = 2011 | doi = 10.1097/PAS.0b013e3182233e06 | PMID = 21753699 }}</ref>
**Typically seen in nonsmokers and younger age patients.
**Typically seen in nonsmokers and younger age patients.
**Can be treated with ''[[crizotinib]]''.<ref name=pmid21475126>{{Cite journal  | last1 = Crystal | first1 = AS. | last2 = Shaw | first2 = AT. | title = New targets in advanced NSCLC: EML4-ALK. | journal = Clin Adv Hematol Oncol | volume = 9 | issue = 3 | pages = 207-14 | month = Mar | year = 2011 | doi =  | PMID = 21475126 }}</ref>
**Can be treated with ''[[crizotinib]]''.<ref name=pmid21475126>{{Cite journal  | last1 = Crystal | first1 = AS. | last2 = Shaw | first2 = AT. | title = New targets in advanced NSCLC: EML4-ALK. | journal = Clin Adv Hematol Oncol | volume = 9 | issue = 3 | pages = 207-14 | month = Mar | year = 2011 | doi =  | PMID = 21475126 }}</ref>
***Resistance to [[ALK inhibitors]] may occur due mutations in kinase domain.
***Ceritinib is indicated for tumor with acquired resistance to crizotinib.<ref>{{Cite journal  | last1 = Shaw | first1 = AT. | last2 = Kim | first2 = DW. | last3 = Mehra | first3 = R. | last4 = Tan | first4 = DS. | last5 = Felip | first5 = E. | last6 = Chow | first6 = LQ. | last7 = Camidge | first7 = DR. | last8 = Vansteenkiste | first8 = J. | last9 = Sharma | first9 = S. | title = Ceritinib in ALK-rearranged non-small-cell lung cancer. | journal = N Engl J Med | volume = 370 | issue = 13 | pages = 1189-97 | month = Mar | year = 2014 | doi = 10.1056/NEJMoa1311107 | PMID = 24670165 }}</ref>
*Testing in [[FFPE]] tissue requires ~100 cells.<ref name=pmid25806315>{{Cite journal  | last1 = Popper | first1 = HH. | last2 = Tímár | first2 = J. | last3 = Ryska | first3 = A. | last4 = Olszewski | first4 = W. | title = Minimal requirements for the molecular testing of lung cancer. | journal = Transl Lung Cancer Res | volume = 3 | issue = 5 | pages = 301-4 | month = Oct | year = 2014 | doi = 10.3978/j.issn.2218-6751.2014.10.02 | PMID = 25806315 }}</ref>


==Microscopic==
==Microscopic==
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===Images===
===Images===
<gallery>
Image: ALK positive lung adenocarcinoma -- very low mag.jpg | ALK +ve lung adenoca - very low mag. (WC)
Image: ALK positive lung adenocarcinoma -- low mag.jpg | ALK +ve lung adenoca - low mag. (WC)
Image: ALK positive lung adenocarcinoma -- intermed mag.jpg | ALK +ve lung adenoca - intermed. mag. (WC)
Image: ALK positive lung adenocarcinoma -- high mag.jpg | ALK +ve lung adenoca - high mag. (WC)
Image: ALK positive lung adenocarcinoma -- very high mag.jpg | ALK +ve lung adenoca - very high mag. (WC)
</gallery>
====www====
*[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3400179/figure/f1-cln_67p845/ Lung carcinoma with ALK rearrangement (nih.gov)].<ref name=pmid22892933>{{Cite journal  | last1 = Lopes | first1 = LF. | last2 = Bacchi | first2 = CE. | title = Anaplastic lymphoma kinase gene rearrangement in non-small-cell lung cancer in a Brazilian population. | journal = Clinics (Sao Paulo) | volume = 67 | issue = 7 | pages = 845-7 | month = Jul | year = 2012 | doi =  | PMID = 22892933 }}</ref>
*[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3400179/figure/f1-cln_67p845/ Lung carcinoma with ALK rearrangement (nih.gov)].<ref name=pmid22892933>{{Cite journal  | last1 = Lopes | first1 = LF. | last2 = Bacchi | first2 = CE. | title = Anaplastic lymphoma kinase gene rearrangement in non-small-cell lung cancer in a Brazilian population. | journal = Clinics (Sao Paulo) | volume = 67 | issue = 7 | pages = 845-7 | month = Jul | year = 2012 | doi =  | PMID = 22892933 }}</ref>
*[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3731315/figure/pone-0069794-g002/ Lung carcinoma with ALK rearrangment (nih.gov)]<ref>{{Cite journal  | last1 = Takamochi | first1 = K. | last2 = Takeuchi | first2 = K. | last3 = Hayashi | first3 = T. | last4 = Oh | first4 = S. | last5 = Suzuki | first5 = K. | title = A rational diagnostic algorithm for the identification of ALK rearrangement in lung cancer: a comprehensive study of surgically treated Japanese patients. | journal = PLoS One | volume = 8 | issue = 8 | pages = e69794 | month =  | year = 2013 | doi = 10.1371/journal.pone.0069794 | PMID = 23936355 }}</ref> - [http://www.plosone.org/article/info:doi/10.1371/journal.pone.0069794.g002/largerimage high resolution (plosone.org)].
*[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3731315/figure/pone-0069794-g002/ Lung carcinoma with ALK rearrangment (nih.gov)]<ref>{{Cite journal  | last1 = Takamochi | first1 = K. | last2 = Takeuchi | first2 = K. | last3 = Hayashi | first3 = T. | last4 = Oh | first4 = S. | last5 = Suzuki | first5 = K. | title = A rational diagnostic algorithm for the identification of ALK rearrangement in lung cancer: a comprehensive study of surgically treated Japanese patients. | journal = PLoS One | volume = 8 | issue = 8 | pages = e69794 | month =  | year = 2013 | doi = 10.1371/journal.pone.0069794 | PMID = 23936355 }}</ref> - [http://www.plosone.org/article/info:doi/10.1371/journal.pone.0069794.g002/largerimage high resolution (plosone.org)].
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*TTF-1 +ve.
*TTF-1 +ve.
*ALK +ve.{{fact}}
*ALK +ve.{{fact}}
===Images===
<gallery>
Image: ALK positive lung adenocarcinoma - ALK IHC -- very low mag.jpg | ALK +ve lung adenoca - very low mag. (WC)
Image: ALK positive lung adenocarcinoma - ALK IHC -- low mag.jpg | ALK +ve lung adenoca - low mag. (WC)
Image: ALK positive lung adenocarcinoma - ALK IHC -- intermed mag.jpg | ALK +ve lung adenoca - intermed. mag. (WC)
Image: ALK positive lung adenocarcinoma - ALK IHC -- high mag.jpg | ALK +ve lung adenoca - high mag. (WC)
Image: ALK positive lung adenocarcinoma - ALK IHC -- very high mag.jpg | ALK +ve lung adenoca - very high mag. (WC)
</gallery>


==Molecular==
==Molecular==
*EML4-ALK fusion -- inv(2)(p21p23).<ref name=pmid21245935>{{Cite journal  | last1 = Li | first1 = Y. | last2 = Ye | first2 = X. | last3 = Liu | first3 = J. | last4 = Zha | first4 = J. | last5 = Pei | first5 = L. | title = Evaluation of EML4-ALK fusion proteins in non-small cell lung cancer using small molecule inhibitors. | journal = Neoplasia | volume = 13 | issue = 1 | pages = 1-11 | month = Jan | year = 2011 | doi =  | PMID = 21245935 }}</ref>
*EML4-ALK fusion -- inv(2)(p21p23).<ref name=pmid21245935>{{Cite journal  | last1 = Li | first1 = Y. | last2 = Ye | first2 = X. | last3 = Liu | first3 = J. | last4 = Zha | first4 = J. | last5 = Pei | first5 = L. | title = Evaluation of EML4-ALK fusion proteins in non-small cell lung cancer using small molecule inhibitors. | journal = Neoplasia | volume = 13 | issue = 1 | pages = 1-11 | month = Jan | year = 2011 | doi =  | PMID = 21245935 }}</ref>
**C-terminus of ALK protein fuses with N-terminus portion of partner protein.
***ALK fusion leads to ligand-independent constitutive activation of important pathways in oncogenesis and tumor progression.


Notes:
Notes:
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*[[Lung tumours]].
*[[Lung tumours]].
*[[Lung carcinoma with EGFR mutation]].
*[[Lung carcinoma with EGFR mutation]].
*[[ALK translocation renal cell carcinoma]].


==References==
==References==
Michael
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