Handout Neoplasia

Question 1

Neoplasm (tumor)

Answer 1

autonomous irreversible clonal benign or malignant cell proliferation outside of normal control by contact inhibition, hormones, etc.

Question 2

Malignancy (cancer)

Answer 2

neoplasm invades and/or metastasizes

Question 3

Metastasis

Answer 3

secondary site of tumor discontinuous with the primary site

Question 4

Carcinoma

Answer 4

malignant neoplasm of EPITHELIAL cell origin (epithelium is a purely cellular avascular layer covering and lining all the external and internal surfaces of the body and associated glands)

Question 5

Sarcoma

Answer 5

malignant neoplasm of MESENCHYME-derived tissue (gives rise to connective tissue including bone, cartilage, blood vessels, etc)

Question 6

Teratoma

Answer 6

benign or malignant neoplasm with components of more than one germ cell layer, usually all three (ectoderm, mesoderm, endoderm)

Question 7

Hamartoma

Answer 7

developmental anomaly creating mass of mature but disorganized tissue indigenous to its site

Question 8

Choristoma

Answer 8

ectopic rest or a mass of normal tissue present outside its normal site, a developmental anomaly

Question 9

Polyp

Answer 9

macroscopic projection above a mucosal (or epidermal) surface or bump or nodule on a stalk in or on that surface

stalk = pedunculated
flat = sessile

Question 10

Adenoma

Answer 10

benign epithelial neoplasm forming glands or derived from glands

Question 11

Anaplasia

Answer 11

lack of visible differentiation of malignant tumor cells, giving them the appearance of primitive unspecalized cells

Question 12

Dysplasia

Answer 12

disordered growth, 2 types

(1) congenital embryonically abnormal organization of cells
(2) acquired cellular atypia, usually premalignant

Question 13

Desmoplasia

Answer 13

reactive formation of abundant fibrous stroma by some carcinogens

Question 14

Carcinoma in situ

Answer 14

tissue with all the cytologic (individual cell) features of malignancy without visible invasion

Question 15

Benign vs. Malignancy

Answer 15

BENIGN
- cohesive expansile local growth
- commonly with fibrous capsule
MALIGNANT
- progressively infiltrative invasive local growth
- commonly with destruction of surrounding tissue

Question 16

What are the patterns of metastatic spread and what is typical of them?

Answer 16

Lymphatic (to regional lymph nodes): typical of carcinomas
Hematogenous (to lung or liver): typical of sarcomas
Seeding (of body cavities or surfaces): typical of ovarian carcinoma

Question 17

What are the features of anaplastic cells

Answer 17

• larger size than differentiated cells
• higher nuclear/cytoplasmic ratio: larger nuclei, less cytoplasm
• pleomorphic (varying in size and shape)
• nuclear abnormalities are angulated shape, hyperchromatism, clumped chromatin, mitoses, and nucleoli

Question 18

What are the most common causes of cancer death

Answer 18

lung
breast and prostate
colon
NOTE: the most common types of cancer to cause death are not the same as the incidence of these types

Question 19

When does most cancer occur

Answer 19

55 and 75 years

Question 20

What are some common causes of cancer?

What cancers are linked to smoking?

Answer 20

SMOKING, OBESITY, EtOH, diet, HPV, UV light, asbestos, etc.

Lung (90%), mouth, pharynx, larynx, esophagus, stomach, pancreas, kidneys, bladder

Question 21

6 Hallmarks of Cancer

Answer 21

Self-sufficiency in growth signals
Insensitivity to anti-growth signals
Evasion of apoptosis
Sustained angiogenesis 
Limitless replication potential
Ability to invade tissue and metastasize

Question 22

Tumor Suppressor Genes

Answer 22

Normally apply breaks to cell proliferation.
Takes defects of both alleles to contribute one of the multiple genetic defects necessary for neoplasia (“like having faulty breaks”)

Examples: RB gene, p53, and APC/beta-catenin pathway

Question 23

Oncogenes

Answer 23

Mutated proto-oncogenes; drive autonomous cell growth in many cancers (“like having the accelerator stuck to the floor”)

Examples: HER2, K-RAS, MYC

Question 24

Rb

Answer 24

When Rb is hypophosphorylated, it prevents cell proliferation by binding the transcription factor E2F.

When Rb is phosphorylated by cyclin D-CDK4, cyclin D-CDK6 and cyclin E-CDK2 complexes, it releases E2F. E2F then activates genes starting up cell proliferation.

Question 25

APC tumor suppressor gene

Answer 25

Controls intestinal stem cell proliferation by WNT signaling. APC gene product breaks down beta-catenin so that it does not bind to the transcription factor TCF that turns on genes that drive cell proliferation.

Question 26

What cancers are APC present in?

Answer 26

Present in 100% of colon cancers with familial adenomatosis polyposis, and also in 70% of sporadic colon cancers

Question 27

What is one of the most commonly mutated tumor suppressor genes in neoplasia

Answer 27

p53-encoding tumor suppressor gene named TP53 which is known as the “GUARDIAN OF THE GENOME”

Question 28

What is the role of p53?

Answer 28

prevents prorogation of genetically damaged cells by binding to DNA, arresting the cell cycle to enable DNA repair and initiating apoptosis, if repair is possible

Question 29

Talk about p53’s half-life

Answer 29

Short half-life of about 20 minutes, ended by ubiquitin proteolysis, so more must be continually generated. Biallelic loss of p53 is present in about 70% of tumors.

Question 30

Resistance to p53 is mediated by…

Answer 30

An increase in MDM2 or E6 protein of HPV, which destroy/degrade p53. The response of a tumor to radiation or chemotherapy is mediated by p53, so resistance to p53 confers resistance to chemotherapy

Question 31

What are the tumor suppressor genes in neurofibromatosis?

Answer 31

NF-1 and NF-2

Question 32

What is the NF-1 pathway?

Answer 32

NF-1 gene product neurofibromin activates a GTPase, creating GDP that binds to cell membrane RAS protein, making it inactive so that RAS does not transduce growth factor signals for proliferation. Inherited mutations create neurofibromatosis, type I, with numerous benign neurofibromas d/t second hit mutations.

Question 33

TGF-beta pathway mutations are important in carcinomas of the…

Answer 33

esophagus and colon

Question 34

What is the VHL pathway?

Answer 34

VHL gene product causes ubiquitination and degradation of hypoxia inducible transcription factor-1 (HIF-1a) that would yield increased PDGF and VEGF and tumor angiogenesis

Question 35

Germline VHL mutations cause

Answer 35

kidney cancer, pheochromocytoma (adrenal medullary tumor), retinal angioma, and other tumors with second hit mutations

Question 36

What is HER2?

Answer 36

Formally called HER2/neu or ERB-B2
EGFR receptor overexpressed in 20% of breast cancers, which often respond to blocking the overexpressed receptor with a monoclonal antibody called trastuzumab or two other newer agents, lapatinib or pertuzumab

Question 37

What cancers is HER2 implicated in?

Answer 37

20% of breast cancers and a similar number of adenocarcinomas of other organs

Question 38

What cancers is K-RAS implicated in?

Answer 38

carcinomas of the colon, lung and pancreas

Question 39

What is K-RAS?

Answer 39

K-RAS oncogene codes for a GTPase in the cytoplasm on the inner side of the cell membrane bound to the EGFR. K-RAS carries out signal transduction from cytoplasm to nucleus when EGFR binds growth factors, transducing signals from the cell to proliferate. Binding of GFs to EGFR causes the K-RAS GTPase to make more GDP that generates proteins that ultimately enter the nucleus to deliver the signal

Question 40

Why must you know about a mutation in K-RAS before directing therapy against EGFR?

Answer 40

K-RAS is donwstream from EGFR. If K-RAS is messed up, running all the time, even when not transducing a growth factor signal, upstream therapy directed against the EGFR won’t work.

Question 41

C-MYC is implicated in which cancer?

Answer 41

Burkitt lymphoma

Question 42

L-MYC is implicated in which cancer?

Answer 42

small cell carcinomas of lung