Intracerebral metastases pathophysiology: Difference between revisions

Jump to navigation Jump to search
VisualWikitext
Line 12: Line 12:
Genes involved in the pathogenesis of intracerebral metastases are tabulated below:<ref name="RahmathullaToms2012">{{cite journal|last1=Rahmathulla|first1=Gazanfar|last2=Toms|first2=Steven A.|last3=Weil|first3=Robert J.|title=The Molecular Biology of Brain Metastasis|journal=Journal of Oncology|volume=2012|year=2012|pages=1–16|issn=1687-8450|doi=10.1155/2012/723541}}</ref>
Genes involved in the pathogenesis of intracerebral metastases are tabulated below:<ref name="RahmathullaToms2012">{{cite journal|last1=Rahmathulla|first1=Gazanfar|last2=Toms|first2=Steven A.|last3=Weil|first3=Robert J.|title=The Molecular Biology of Brain Metastasis|journal=Journal of Oncology|volume=2012|year=2012|pages=1–16|issn=1687-8450|doi=10.1155/2012/723541}}</ref>


{| class="wikitable" ! Genes ! Cancer site (primary) ! Role and implications ! Chromosome location |- | RHoC | Melanoma | Regulates remodeling of actin cytoskeleton during morphogenesis and motility. Important in tumor cell invasion | 1p21-p13 |- | LOX | BreastHead and neck cancer | Increases invasiveness of hypoxic human cancer cells through cell matrix adhesion and focal adhesion kinase activity | 5q23.1-q23.2 |- | VEGF | LungBreastMelanomaColon | Angiogenic growth factorInhibition decreases brain metastasis formation; reduces blood vessel formation and cell proliferation; increases apoptosis | 6p21.1 |- | CSF1 | BreastLung | Stimulate macrophage proliferation and subsequent release of growth factors | 1p13.3 |- | ID1 | BreastLung | Involved in matrix remodeling, intracellular signaling, and angiogenesis | 20q11.21 |- | TWIST1 | BreastGastricRhabdomyosarcomaMelanomaHepatocellular | Causes loss of E-cadherin-mediated cell-cell adhesion, activates mesenchymal markers, and induces cell motility by promoting epithelial-mesenchymal transition | 7p21.1 |- | MET | Renal cell cancer | Affects a wide range of biological activity depending on the cell target, varying from mitogenesis, morphogenesis, and motogenesis | 7q31.2 |- | MMP-9 | ColorectalBreastMelanomaChondrosarcoma | Extracellular matrix degradation, tissue remodeling | 20q13.12 |- | NEDD9 | Melanoma | Acquisition of a metastatic potential | 6p24.2 |- | LEF1 | Lung | Transcriptional effecter—WNT pathway; predilection for brain metastasisKnockdown inhibits brain metastasis, decreases colony formation; in vitro decreases invasion | 4q25 |- | HOXB9 | LungBreast | Homeobox gene family; critical for embryonic segmentation and patterning. Also a TCF4 targetKnockdown in vitro decreased invasion and colony formation; in vivo appears to inhibit brain metastasis | 17q21.32 |- | BMP4 | LungColorectal | Plays an essential role in embryonic development and may be an essential component of the epithelial-mesenchymal transition | 14q22.2 |- | STAT3 | Melanoma | Cell signaling transcription factorReduction suppresses brain metastasis; decreases angiogenesis in vivo and cellular invasion in vitro | 17q21.2 |}
{| class="wikitable"  
! style="background: #4479BA; width: 150px;" | {{fontcolor|#FFF|Genes}}
! style="background: #4479BA; width: 150px;" | {{fontcolor|#FFF|Cancer site (primary)}}
! style="background: #4479BA; width: 150px;" | {{fontcolor|#FFF|Role and implications}}
! style="background: #4479BA; width: 150px;" | {{fontcolor|#FFF|Chromosome location}}
|-  
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" align=center |RHoC  
| Melanoma  
| Regulates remodeling of actin cytoskeleton during morphogenesis and motility  
Important in tumor cell invasion  
| 1p21-p13  
|-  
| LOX  
| Breast
Head and neck cancer
| Increases invasiveness of hypoxic human cancer cells through cell matrix adhesion and focal adhesion kinase activity  
| 5q23.1-q23.2  
|-  
| VEGF  
| Lung
Breast
Melanoma
Colon
| Angiogenic growth factor
Inhibition decreases brain metastasis formation; reduces blood vessel formation and cell proliferation; increases apoptosis  
| 6p21.1  
|-  
| CSF1  
| Breast
Lung
| Stimulate macrophage proliferation and subsequent release of growth factors  
| 1p13.3  
|-  
| ID1  
| Breast
Lung
| Involved in matrix remodeling, intracellular signaling, and angiogenesis  
| 20q11.21  
|-  
| TWIST1  
| Breast
Gastric
Rhabdomyosarcoma
Melanoma
Hepatocellular
| Causes loss of E-cadherin-mediated cell-cell adhesion, activates mesenchymal markers, and induces cell motility by promoting epithelial-mesenchymal transition  
| 7p21.1  
|-  
| MET  
| Renal cell cancer  
| Affects a wide range of biological activity depending on the cell target, varying from mitogenesis, morphogenesis, and motogenesis  
| 7q31.2  
|-  
| MMP-9  
| Colorectal
Breast
Melanoma
Chondrosarcoma
| Extracellular matrix degradation, tissue remodeling  
| 20q13.12  
|-  
| NEDD9  
| Melanoma  
| Acquisition of a metastatic potential  
| 6p24.2  
|-  
| LEF1  
| Lung  
| Transcriptional effecter—WNT pathway; predilection for brain metastasis
Knockdown inhibits brain metastasis, decreases colony formation; in vitro decreases invasion  
| 4q25  
|-  
| HOXB9  
| Lung
Breast
| Homeobox gene family; critical for embryonic segmentation and patterning. Also a TCF4 target
Knockdown in vitro decreased invasion and colony formation; in vivo appears to inhibit brain metastasis  
| 17q21.32  
|-  
| BMP4  
| Lung
Colorectal
| Plays an essential role in embryonic development and may be an essential component of the epithelial-mesenchymal transition  
| 14q22.2  
|-  
| STAT3  
| Melanoma  
| Cell signaling transcription factor
Reduction suppresses brain metastasis; decreases angiogenesis in vivo and cellular invasion in vitro  
| 17q21.2  
|}


===Gross Pathology===
===Gross Pathology===

Revision as of 19:51, 10 November 2015

Intracerebral metastases Microchapters

Home

Patient Information

Overview

Historical Perspective

Classification

Pathophysiology

Causes

Differentiating Intracerebral Metastases from other Diseases

Epidemiology and Demographics

Risk Factors

Screening

Natural History, Complications and Prognosis

Diagnosis

Staging

History and Symptoms

Physical Examination

Laboratory Findings

Chest X Ray

CT

MRI

Ultrasound

Other Imaging Findings

Other Diagnostic Studies

Treatment

Medical Therapy

Surgery

Primary Prevention

Secondary Prevention

Cost-Effectiveness of Therapy

Future or Investigational Therapies

Case Studies

Case #1

Intracerebral metastases pathophysiology On the Web

Most recent articles

Most cited articles

Review articles

CME Programs

Powerpoint slides

Images

American Roentgen Ray Society Images of Intracerebral metastases pathophysiology

All Images
X-rays
Echo & Ultrasound
CT Images
MRI

Ongoing Trials at Clinical Trials.gov

US National Guidelines Clearinghouse

NICE Guidance

FDA on Intracerebral metastases pathophysiology

CDC on Intracerebral metastases pathophysiology

Intracerebral metastases pathophysiology in the news

Blogs on Intracerebral metastases pathophysiology

Directions to Hospitals Treating Intracerebral metastases

Risk calculators and risk factors for Intracerebral metastases pathophysiology

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]Associate Editor(s)-in-Chief: Sujit Routray, M.D. [2]

Overview

Pathophysiology

Pathogenesis

Genetics

Genes involved in the pathogenesis of intracerebral metastases are tabulated below:[1]

Genes Cancer site (primary) Role and implications Chromosome location
RHoC Melanoma Regulates remodeling of actin cytoskeleton during morphogenesis and motility

Important in tumor cell invasion

1p21-p13
LOX Breast

Head and neck cancer

Increases invasiveness of hypoxic human cancer cells through cell matrix adhesion and focal adhesion kinase activity 5q23.1-q23.2
VEGF Lung

Breast Melanoma Colon

Angiogenic growth factor

Inhibition decreases brain metastasis formation; reduces blood vessel formation and cell proliferation; increases apoptosis

6p21.1
CSF1 Breast

Lung

Stimulate macrophage proliferation and subsequent release of growth factors 1p13.3
ID1 Breast

Lung

Involved in matrix remodeling, intracellular signaling, and angiogenesis 20q11.21
TWIST1 Breast

Gastric Rhabdomyosarcoma Melanoma Hepatocellular

Causes loss of E-cadherin-mediated cell-cell adhesion, activates mesenchymal markers, and induces cell motility by promoting epithelial-mesenchymal transition 7p21.1
MET Renal cell cancer Affects a wide range of biological activity depending on the cell target, varying from mitogenesis, morphogenesis, and motogenesis 7q31.2
MMP-9 Colorectal

Breast Melanoma Chondrosarcoma

Extracellular matrix degradation, tissue remodeling 20q13.12
NEDD9 Melanoma Acquisition of a metastatic potential 6p24.2
LEF1 Lung Transcriptional effecter—WNT pathway; predilection for brain metastasis

Knockdown inhibits brain metastasis, decreases colony formation; in vitro decreases invasion

4q25
HOXB9 Lung

Breast

Homeobox gene family; critical for embryonic segmentation and patterning. Also a TCF4 target

Knockdown in vitro decreased invasion and colony formation; in vivo appears to inhibit brain metastasis

17q21.32
BMP4 Lung

Colorectal

Plays an essential role in embryonic development and may be an essential component of the epithelial-mesenchymal transition 14q22.2
STAT3 Melanoma Cell signaling transcription factor

Reduction suppresses brain metastasis; decreases angiogenesis in vivo and cellular invasion in vitro

17q21.2

Gross Pathology

  • Typically metastases are sharply demarcated from the surrounding parenchyme and usually there is a zone of peritumoral edema out of proportion with the tumor size.
  • Common intracranial sites associated with subependymal giant cell astrocytoma include:[2]

Gallery

  • This solitary brain metastasis from thyroid papillary carcinoma resulted in neurological symptoms. The thyroid primary was clinically occult. (Courtesy of Dr. Nikola Kostich, Minneapolis, MN.).[3]

    This solitary brain metastasis from thyroid papillary carcinoma resulted in neurological symptoms. The thyroid primary was clinically occult. (Courtesy of Dr. Nikola Kostich, Minneapolis, MN.).[3]

Microscopic Pathology

The histopathological appearance of intracerebral metastases may vary with the type of primary tumor. Common findings are listed below:[4][5]

  • Tubule formation/glands
  • Well-circumscribed and sharply demarcated from surrounding tissue (with the exception of melanoma metastasis)
  • Mitoses
  • Nuclear atypia
  • Nuclear hyperchromasia
  • Variation of nuclear size
  • Variation of nuclear shape

Gallery

  • Very low magnification micrograph demonstrating metastatic adenocarcinoma that from a colorectal primary, i.e. colorectal carcinoma, by immunostains on HPS stain. The cerebellum seen on the image has Bergmann gliosis and Purkinje cell loss.[6]

    Very low magnification micrograph demonstrating metastatic adenocarcinoma that from a colorectal primary, i.e. colorectal carcinoma, by immunostains on HPS stain. The cerebellum seen on the image has Bergmann gliosis and Purkinje cell loss.[6]

  • High magnification micrograph demonstrating metastatic adenocarcinoma that is from a colorectal primary, i.e. colorectal carcinoma, by immunostains on HPS stain. The cerebellum has Bergmann gliosis and Purkinje cell loss.[6]

    High magnification micrograph demonstrating metastatic adenocarcinoma that is from a colorectal primary, i.e. colorectal carcinoma, by immunostains on HPS stain. The cerebellum has Bergmann gliosis and Purkinje cell loss.[6]

  • High magnification micrograph of a brain metastasis on HPS stain demonstrating normal brain tissue on the left and tumor cells on the right. The sharp demarcation between tumor and normal is typical of brain metastases.[6]

    High magnification micrograph of a brain metastasis on HPS stain demonstrating normal brain tissue on the left and tumor cells on the right. The sharp demarcation between tumor and normal is typical of brain metastases.[6]

  • Adenocarcinoma infiltrating the brain in a case of lung cancer on H&E stain.[6]

    Adenocarcinoma infiltrating the brain in a case of lung cancer on H&E stain.[6]

Immunohistochemistry

  • The immunohistochemistry profile of intracerebral metastases may vary with the type of the primary tumor.[7]
  • Intracerebral metastases are demonstrated by positivity to tumor markers such as:[7]

Gallery

  • Immunohistochemistry profile of intracerebral metastases from an adenocarcinoma of lung (primary) demonstrating positivity to CK7, CK20, and TTF1.[8]

    Immunohistochemistry profile of intracerebral metastases from an adenocarcinoma of lung (primary) demonstrating positivity to CK7, CK20, and TTF1.[8]

References

  1. ↑ Rahmathulla, Gazanfar; Toms, Steven A.; Weil, Robert J. (2012). "The Molecular Biology of Brain Metastasis". Journal of Oncology. 2012: 1–16. doi:10.1155/2012/723541. ISSN 1687-8450.
  2. ↑ Khuntia, Deepak (2015). "Contemporary Review of the Management of Brain Metastasis with Radiation". Advances in Neuroscience. 2015: 1–13. doi:10.1155/2015/372856. ISSN 2356-6787.
  3. ↑ Gross image of brain metastases. Libre pathology 2015. http://librepathology.org/wiki/index.php/Brain_metastasis. Accessed on November 10, 2015
  4. ↑ Microscopic features of brain metastasis. Libre pathology 2015. http://librepathology.org/wiki/index.php/Brain_metastasis. Accessed on November 10, 2015
  5. ↑ Microscopic appearance of brain metastases. Dr Bruno Di Muzio and Dr Trent Orton et al. Radiopaedia 2015. http://radiopaedia.org/articles/brain-metastases. Accessed on November 10, 2015
  6. ↑ 6.0 6.1 6.2 6.3 Microscopic images of brain metastasis. Libre pathology 2015. http://librepathology.org/wiki/index.php/Brain_metastasis. Accessed on November 10, 2015
  7. ↑ 7.0 7.1 IHC features of brain metastasis. Libre pathology 2015. http://librepathology.org/wiki/index.php/Brain_metastasis. Accessed on November 10, 2015
  8. ↑ IHC image of brain metastasis. Libre pathology 2015. http://librepathology.org/wiki/index.php/Brain_metastasis. Accessed on November 10, 2015


Template:WikiDoc Sources

Retrieved from "https://www.wikidoc.org/index.php?title=Intracerebral_metastases_pathophysiology&oldid=1185381"