15.3 - Cancer Biology Flashcards
Clinically-usefl classes of breast cancer
- ER+
- PR+
- HER2/neu+
- triple negative
What are two genes some familial cancers are linked to
- BRCA1
- BRCA2
Skin Cancers
- include
1) Keratomas
2) Melanomas - these cancers typically have two phases
A) radial growth phase
B) Vertical growth phase
Staging of skin and breast cancer
- by considering their size and mitotic frequency
- extent of tissue layers invaded
- whether cancerous cells have entered sentinel lymph nodes
Metastases
- in the most dangerous cancers
- those that have managed to proceed through the entire lymph drainage and entered the blood
- have potential to produce new growths at distant, unrelated sites in body
Breast Cancer
- affects 1:8 women
- incidence increases dramatically with age
- most originate in ductal cells
- minority originate in secretory cells
- anti-estrogen durgs (tamoxifen) have been used for several decades with varying degrees of success
- 2-5% have of breast + ovarian cancers have mutated in genes BRCA1 and BRCA2 (risk increased to 50-80% in germline mutation)
BRCA1 and BRCA2
- mutated in 2-5% of breast and ovarian cancers
- mutation in the germ line increases the risk to 50-80%
- both function ubiquitously in DNA repair and regulation of transcription
Current state of breast cancer treatments involves first assessing the state of receptor expression on the cancerous cells, what are the 4 patterns of expression that have been identified and their respective targeted treatments
1) Express the estrogen receptor
- classical anti-estrogen drugs
2) Expresse the progesterone receptor
- also have pharmacologic treatments
3) Express the epidermal growth factor receptor (HER2/neu)
- treatments based on monoclonal antibodies
4) triple negative (minority group)
- express none of the previous 3 receptors
- treated with non-specific chemotherapy agents
- soon be candidates for emerging personalized medicine
What is personalized medicine
= emerging field
- triple negative cancers may be candidates for this treatment soon
= treatment involves knowledge of the particularities of a individual patient’s genome
3 cancers commonly arising from cells in the integument and their associated cells
1) squamous cell carcinoma = keratinocytes
2) basal cell carcinoma = stratum basale keratinocytes
3) Melanomas = melanocytes
Melanoma
- typically linked with more fatality - presumably having something to do with the fact that the melanocyte is intrinsically capable of more migration
- progresses within the epidermis in two phases
1) Radial Growth Phase
2) Vertical Growth Phase
Radial Growth phase in melanomas
- the most noticeable cellular migration occurs parallel to the skin surface
Vertical growth phase in melanomas
- cells stack perpendicular to the surface
- 1st increasing the thickness of the epithelium
- 2nd breaching the BM to invade underlying tissues
Describe the staging of melanoma based on the tissue layers breached
- Level 1 = malignant cell clusters are confined to the epidermis
- Level 2 = Clusters invade the dermal papillae
- Level 3 = clusters reach to the reticular dermis
- Level 4 = clusters invade the reticular dermis
- Level 5 = clusters invade the hypodermis
What does level 1 staging of melanoma signify?
- malignant cell clusters are confined to the epidermis
What does level 2 staging of melanoma signify?
- clusters invade the dermal papillae
What does level 3 staging of melanoma signify?
- clusters reach to the reticular dermis
What does level 4 staging of melanoma signify?
- clusters invade the reticular dermis
What does level 5 staging of melanoma signify?
- clusters invade the hypodermis
What occurs once malignant cells invade the CT (i.e. post stage level 5 melanoma)?
- Immune response is generated
- tumor-infiltrating lymphocytes are seen in great numbers
- this used with other observable factors is used to predict melanoma prognosis
A) tumor thickness
B) ulceration
C) mitotic rate - in more advanced cases tumor cells travel via the lymphatic system
What are sentinel lymph nodes and their relevance to cancer/tumors/metastasis
= the first lymph nodes along the path of drainage from the affected region
- if tumor cells are present –> investigate successive nodes up the lymphatic chain towards L or R thoracic ducts
- -> important because most of the body bronchopulmonary nodes are part of this chain
- which is why metastases to the lung tissue are common in melanoma
Tumor cells present in the last nodes before lymph is drained via the thoracic duct into the systemic circulation indicates what?
- distant metastases, far from site of origin are possible
= much poorer prognosis
Describe the staging of cancer based on progression through the lymphatics
- considered in N and M categories for melanoma and often for other types of cancers (Colon, prostate, also breast cancer due to well studied lymphatic drainage)
- NX = regional nodes cannot be assessed
- N0 = no spread to adjacent nodes
- N1 = spread to one node
- N1a = diagnosed on pathology
- N1b = detectable clinically
- N2 = spread to 2-3 nearby nodes
- N2a = diagnosed on pathology
- N2b = detectable clinically
- N3 = spread to 4 or more nodes
- M0 = no evidence of distant metastases
- M1a = metastases to skin, sub-q or distant lymph nodes
- M1b = metastases to lung
- M1c = all other metastases
What does NX cancer staging of progression through the lymphatic signify?
= regional nodes cannot be assessed
What does N0 cancer staging of progression through the lymphatic signify?
= no spread to adjacent nodes
What does N1a cancer staging of progression through the lymphatic signify?
= spread to 1 node
- diagnosed on pathology
What does N1b cancer staging of progression through the lymphatic signify?
= spread to 1 node
- detectable clinically
What does N2a cancer staging of progression through the lymphatic signify?
= spread to 2-3 nearby nodes
- diagnosed on pathology
What does N2b cancer staging of progression through the lymphatic signify?
= spread to 2-3 nearby nodes
- detectable clinically
What does N3 cancer staging of progression through the lymphatic signify?
= spread to 4 or more nodes
What does M0 cancer staging of progression through the lymphatic signify?
= no evidence of distant metastases
What does M1a cancer staging of progression through the lymphatic signify?
= metastases to skin, sub-1 or distant lymph nodes
What does M1b cancer staging of progression through the lymphatic signify?
= metastases to lung
What does M1c cancer staging of progression through the lymphatic signify?
= all other metastases
Describe the pattern of lymphatic drainage from the breast
= 75% of the breast volume drains laterally to axillary nodes
= 25% drains medially to various lymph nodes of the internal mammary chain
Describe the other cancers that staging by layers is useful for, and how
1) Cancers of the GI tract
- most lymph drainage occurs from the submucosal layer
- -> penetration of the muscularis mucosae layer is an important landmark for GI-system cancers
2) Bladder cancers
- muscularis mucosae in the bladder is a particularly challenging but important landmark in bladder cancer staging
