Handout Neoplasia Flashcards by Katherine DiGiovanni

Neoplasm (tumor)

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

How well did you know this?

Not at all

Perfectly

Malignancy (cancer)

neoplasm invades and/or metastasizes

How well did you know this?

Not at all

Perfectly

Metastasis

secondary site of tumor discontinuous with the primary site

How well did you know this?

Not at all

Perfectly

Carcinoma

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)

How well did you know this?

Not at all

Perfectly

Sarcoma

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

How well did you know this?

Not at all

Perfectly

Teratoma

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

How well did you know this?

Not at all

Perfectly

Hamartoma

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

How well did you know this?

Not at all

Perfectly

Choristoma

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

How well did you know this?

Not at all

Perfectly

Polyp

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

stalk = pedunculated
flat = sessile

How well did you know this?

Not at all

Perfectly

Adenoma

benign epithelial neoplasm forming glands or derived from glands

How well did you know this?

Not at all

Perfectly

Anaplasia

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

How well did you know this?

Not at all

Perfectly

Dysplasia

disordered growth, 2 types

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

How well did you know this?

Not at all

Perfectly

Desmoplasia

reactive formation of abundant fibrous stroma by some carcinogens

How well did you know this?

Not at all

Perfectly

Carcinoma in situ

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

How well did you know this?

Not at all

Perfectly

Benign vs. Malignancy

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

How well did you know this?

Not at all

Perfectly

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

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

How well did you know this?

Not at all

Perfectly

What are the features of anaplastic cells

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

What are the most common causes of cancer death

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

When does most cancer occur

55 and 75 years

What are some common causes of cancer?

What cancers are linked to smoking?

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

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

6 Hallmarks of Cancer

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

Tumor Suppressor Genes

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

Oncogenes

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

Examples: HER2, K-RAS, MYC

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.

APC tumor suppressor gene

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.

What cancers are APC present in?

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

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

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

What is the role of p53?

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

Talk about p53's half-life

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.

Resistance to p53 is mediated by...

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

What are the tumor suppressor genes in neurofibromatosis?

NF-1 and NF-2

What is the NF-1 pathway?

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.

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

esophagus and colon

What is the VHL pathway?

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

Germline VHL mutations cause

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

What is HER2?

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

What cancers is HER2 implicated in?

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

What cancers is K-RAS implicated in?

carcinomas of the colon, lung and pancreas

What is K-RAS?

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

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

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.

C-MYC is implicated in which cancer?

Burkitt lymphoma

L-MYC is implicated in which cancer?

small cell carcinomas of lung