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MOD 3 > Invasion and Metastasis Pathology > Flashcards

Invasion and Metastasis Pathology Flashcards

1
Q

Most frequent metastasis of lung cancers:

A
  • adrenals (>50%)
  • liver (30-50%)
  • brain (20%)
  • bones (20%)
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2
Q

Most frequent metastasis of breast cancers:

A
  • lungs
  • bones
  • liver
  • adrenals
  • brain
  • meninges
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3
Q

Most frequent metastasis of prostate cancers:

A
  • bones
    • lumbar spine
    • proximal femur
    • pelvis
    • thoracic spine
    • ribs
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4
Q

Most frequent metastasis of colorectal cancers

A
  • liver
  • lungs
  • bones
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5
Q

Not all malignant tumors metastasize. What is a classic example?

A

Basal cell carcinomas of the skin

  • common, slow-growing and malignant
  • rarely metastaize (less than 0.01%)
  • locally invasive
  • if allowed to grow, kill by invasion
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6
Q

Define sentinel lymph node

A

the first node in a regional lymphatic basin that receives lymph flow from the primary tumor

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7
Q

What are the three components of metastatic dissemination?

A
  1. Seeding
  2. Hematogenous spread
  3. Lymphatic spread
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8
Q

define Seeding

A
  • component of metastatic dissemination
  • peritoneum, pleural cavity, pericardium, subarachnoid, joint spaces
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9
Q

Define hematogenous spread. What’s type of cancer typically does this?

A
  • metastasis through the blood rout
  • typical of most sarcomas, but carcinomas also do this
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10
Q

Define lymphatic spread. This is the most common pathway for which type of cancer? Explain what type of lymphatic spread you see in breast and lung cancers

A

Metastatic dissemination through lymph nodes

  • Most common pathway for initial dissemination of carcinomas (less comonly used by sarcomas)
  • Breast carcinoma –> axillary lymph nodes
  • Lung carcinomas –> perihilar tracheobronchila and medistinal lymph nodes)
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11
Q

Describe the kinetics of invasion and metastasis

A

Primary tumor (proliferation + angiogenesis) –> local invasion [detachment/EMT/embolization/criculation/survival/arrest in distant organs/adherence to vessel wall/extravasation] –> proliferation/angiogenesis –> **metastasis **

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12
Q

Metastases in liver, brain, and adrenals of a 66-yo pt are most likely derived from a primary cancer of:

a. prostate
b. esophagus
c. breast
d. lung
e. colon

A

lung

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13
Q

A 70-yo pt presents with pain in the lower back. His PSA and alkaline phosphatase levels are elevated and xrays show multiple radiodense lesions in the lumbar vertebrae. Which of the following is most likely primary cancer?

a. prostate
b. esophagus
c. breast
d. lung
e. colon

A

a. prostate

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14
Q

You detect a firm, non-moveable mass in female right breast (52 yo) as well as firm painless nodules in the right axilla. A needle biopsy confirms the suspicion of breast cancer requiring mestectomy and axillary lymphnode dissection. Carcinoma cells have invated 5 lymph nodes. Which characteristic of cancer cells is most likely involved in metastatic dissemination of these lymph nodes?

a. decreased apoptosis
b. overexpression of keratin
c. switch to N-cadherin
d. overexpression of ß-1 integrin
e. increased angiogenesis

A

c. switch to N-cadherin

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15
Q

exact definition of metastasis

A

when tumor spreads from primary neoplasm to distant organs (where the cells then grow relentlessly)

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16
Q

What is “epigenetic switch” in neoplasia and provide an example

A
  • critical but potentially transient changes in gene expression patterns can occur as cancer cells invade local tissues and metastasize to distant sites
    • does not alter the DNA sequence itself
  • hypermethylation causes silencing of certain tumor suppressor genes
  • demethylation of silenced genes can also occur
  • ex: loss of cell adhesion at beginning of invasion and reacquisition of adhesion at distant site
17
Q

How do cancer cells modify their stromal environment and activate stromal cells?

A
  • cancer cells produce cytokines and proteolytic enzymes
  • activated fibroblasts, adipocytes, and inflammatory cells in tumor stroma produce cytokines, proteolytic enzymes, and pro-migratory ECM components
18
Q

Describe 3 important cancer-host interactions

A
  1. basement membrane degradation: cancer cell can get in contact with stromal fibroblasts and change their phentoype to that of myofibroblasts
  2. invading tumor cells secrete cytokines to stimulate **angiogenesis **and lymphangiogenesis (VEGF-A, -C, -D)
  3. activated myofibroblasts, tumor-associated macrophages, and cancer cells secrete **ECM-degrading enzymes **(MMPs, cathepsin) and cytokines that further stimulate stromal cells and cancer cell invasion
19
Q

3 main functions of cytokines in neoplasia

A
  1. Pro-tumor effects
    1. stimulate cell growth, angiogenesis, and metastasis, loss of growht control by TGFß
  2. immune suppresion
  3. systemic effects (cachexia)
20
Q

example of over-expressed cytokine receptor

A

EGFR

-HER/erbB family of receptor tyrosine kinases (RTKS)

  • HER1 (EGFR/erbB1)
  • HER2 (neu, erbB2)
  • HER3 (erbB3)
  • HER4 (erbB4)
21
Q

Explain the changes in adhesion in metastasis

A
  • differential expression of attachment and adhesion factors plays important role in invasion and metastasis
  • malignant tumor cells **lose their attachment to each other **and their adhesive interactions with the basement membrane
  • accomplished through changes in **cadherins, integrines, **and their **receptors **
22
Q

Describe the remodeling of ECM

-what correlates with degree of invasion and metastatic potential?

A
  • Proteolysis
    • matrix metalloproteinases (MMPs)
    • tissue inhibition of MMPs (TIMPs)
    • plasminogen activator family (uPa)
  • interaction with cells of ECM
  • increase levels/activity of MMPs correlates with degree of invasion and metastatic potential
  • relationship between MMPs and TIMPs determines the balance between **matrix degradation **and **matrix formation **
23
Q

anoikis and cancer progression

recall: anoikis = death of homelessness

A

most cancer cells of EPITHELIAL ORIGIN are anoikis resistant

24
Q
A

MOD 3 (19 decks)

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