Ch 7: neoplasia Flashcards Preview

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Flashcards in Ch 7: neoplasia Deck (178):
1

desmoplasia

abundant collagenous stroma

2

scirrhous

desmoplastic tumors that are stony and hard

3

adenoma

• Adenoma is used for benign epithelial neoplasm derived from glands

4

papilloma

= benign epithelial neoplasms producing microscopically visible finger-like or warty projections from endothelial cells

5

cystadenoma

adenomas that form large cystic masses

6

polyp

when a neoplasm benign or malignant produces a macroscopically visible projection above the mucosal surface and projects into the lumen

7

sarcoma

are malignant tumors that arise from mesenchymal tissue
o sar means fleshy: they have little CT stroma
o ex. fibrosarcoma, chondrosarcome, leiomyosarcoma

8

carcinomas

carcinomas are malignant neoplasms of epithelial cell origin, derived from any of the three layers
o ex. squamous cell carcinoma,
o adenocarcinoma: lesion where neoplastic epithelial cells grow in glandular patterns

9

pleomorphic adenoma

o Pleomorphic adenoma: all these elements arise from a single clone capable of giving rise to epithelial and myoepithelial cells

10

teratoma: two types?

contains recognizable mature or immature cells or tissues representative of more than one germ cell layer and sometimes all three
o originate from totipotential cells
o Mature teratoma, dermatoid cyst = benign teratoma = components are well differentiated
o Immature teratoma, teratocarcinoma = malignant teratoma = components are immature

11

hamartoma

disorganized but benign appearing masses composed of cells indigenous to the particular site
• ex. pulmonary chondroid harmatoma = islands of disorganized but histologically normal cartilage, bronchi and vessels

12

Squamous keratinocytes

Squamous keratinocytes: Squamous cell papilloma Squamous cell carcinoma

13

Epidermal basal cells

Basal cell carcinoma

14

gland/duct epithelium

Adenoma Adenocarcinoma
Papilloma
Papillary carcinoma
Cystadenoma Cystadenocarcinoma

15

resp epithelium

Bronchial adenoma Bronchogenic carcinoma

16

renal tubule epithelium

Renal tubular adenoma Renal cell carcinoma

17

hepatocytes

Liver cell adenoma Hepatocellular carcinoma

18

transitional epithelium

Urothelial papilloma Urothelial carcinoma

19

placental epithelium

Hydatidiform mole Choriocarcinoma

20

testicular germ cells

Seminoma
Embryonal carcinoma
(both are malignant)

21

skin,squamous mucosa (melanocytes)

Nevocellular nevus (benign) Malignant melanoma

22

fibroconnective CT

Fibroma Fibrosarcoma

23

adipose CT

Lipoma Liposarcoma

24

Cartilage CT

Chondroma Chondrosarcoma

25

bone

Osteoma Osteogenic sarcoma

26

blood vessels

Hemangioma Angiosarcoma

27

lymph vessels

Lymphangioma Lymphangiosarcoma

28

synovium

malignant only
Synovial Sarcoma

29

mesothelium

only malignant
mesothelioma

30

Brain coverings

Meningioma
Invasive Meningioma

31

bone marrow

leukemia (malignant)

32

nodal/extranodal

lymphoma (malignant)

33

smooth muscle

Leiomyoma Leiomyosarcoma

34

striated mm.

Rhabdomyoma Rhabdomyosarcoma

35

anaplasia

lack of differentiation
• malignant neoplasms that are composed of poorly differentiated cells are anaplastic
• lack of differentiation is considered a hallmark of malignancy

36

pleomorphism

variation of size and shape of nuclei

37

metaplasia

replacement of one type of cell with another
• almost always found in assoc. w/ tissue damage, repair and regeneration

38

dysplasia

= disordered growth
• often occurs in metaplastic epithelium, but not all metaplasia is dysplastic

39

carcinoma in situ

when dysplastic changes involve entire thickness of epithelium but the lesion remains confined by the basement membrane and is a preinvasive neoplasm

40

3 things affecting rate of tumor growth?

o doubling time of tumor cells
o growth fraction = fraction of tumor cells in the replicative pool- as tumors continue to grow, cells leave the proliferative pool due to shedding, lack of nutreints, necrosis, apoptosis and thus by the time tumor is clinically detectable, most cells are not in the proliferative pool
o rate at which cells shed/divide

41

TIC's

• Tumor Initiating Cells: cells that allow a human tumor to grow and maintain itself indefinitely when transplanted into an immunodeficient mouse
o like “leukemia stem cells”
o TIC’s seem to be very common in some types of cancers
o Tumors may have a small number of TIC’s that then “differentiate” to form the bulk of the tumor, while others are largely composed of TIC’s

42

fibrous capsule

benign tumors grow and expand slowly, thus they usually develop a rim of compressed CT around them
o encapsulation doesn’t prevent tumor growth, but it keeps benign neoplasm as a discrete, readily palpable, easily movable mass
o not all benign neoplasms are encapsulated – uterine leiomyomas have not capsule, but have well-defined cleavage planes

43

two exceptions to metastasis rule?

malignant neoplasms of glial cells in CNS (gliomas) and basal cell carcinomas are considered malignant but they DO NOT metastasize, and are locally invasive

44

lymphatic spread

most common in carcinomas
• ex. breast in upper quadrant →axillary lymph nodes
• ex. inner quadrant of breast → nodes along internal mammary aa. (infraclavicular and supraclavicular nodes)
• ex. carcinomas of lung arising in major respiratory passages → perihlar tracheobronchial and mediastinal nodes

45

hematogenous spread: breast? bronchogenic? renal cell carcinoma? neuroblastoma?

***sarcomas – most lethal route! – go to brain, bone, liver and lung!

• (liver and lungs are most frequently involved in dissemination)
• cancers arising close to vertebral column often embolize through paravertebral plexus
• ex. renal cell carcinoma: often invades branches of renal v. to grow in snakelike fashion up IVC
• breast carcinoma → bone
• bronchogenic carcinoma → adrenals and brain
• neuroblastomas → liver and bones

46

renal cell carcinoma

renal V and IVC

47

hepatocellular carcinomas

portal radicles into vv.

48

adenocarcinoma of colon

liver via portal system

49

prostatic carcinoma

bone via vascular plexuses

50

small cell carcinomas of lung

adrenals and brain

51

lobular carcinoma of breast

CNS/meninges

52

breast carcinoma

bone

53

neuroblastoma

liver and bones

54

blue cell tumors

seen in infancy/childhood – neuroblastoma, Wilms tumor, retinoblastoma, acute leukemias, rhabdomyosarcomas

55

AD mutation of BRCA1/BRCA2

= breast cancer suscpetilbity
• familal cancer
= ovarian cancer

56

AD mutation of mutation of p16INK4a tumor suppressor

familal melanoma

57

AD mutation of Rb

1. Childhood Retinoblastoma:
- due to mutation in RB tumor suppressor gene
- children develop a retinoblastoma, increased chance of developing osteosarcoma

58

AD APC mutation

caused by mutation of adenomatous polyposis coli (APC) tumor suppressor gene.
- develop innumerable polypoid ademoas of colon and develop colonic adenocarcinoma by age 50

59

AD p53 mutation

3. Li-Fraumeni syndrome: results from germiline mutations of p53 gene
- not tissue specific

60

AD MEN-1 and RET mutation

Multiple endocrine Neoplasia types 1 and 2 (MEN-1 and MEN-2): mutation of genes that encode the menin txn factor and the RET tyrosin kinase respectively
- MEN-1: pituitary, parathyroid, pancreas
- MEN-2: thyroid, parathyroid, adrenals
f

61

AD mutation of MSH2, MLH1, MSH6

Hereditary nonpolyposis colon cancer: caused by inactivation of a DNA mismatch repair gene
* most common cancer predisposition syndrome
o increases susceptibility to cancer of colon, small intestine, endometrium and ovary

62

AD mutation of PATCH

Nevoid basal cell carcinoma syndrome

63

AD mutatoin of NF1/NF2

Neurofibromatosis 1 and 2

64

chronic inflammation

o inflammatory GI diseases increase risk of cancer: ulcerative colitis, Helicobacter pylori gastritis, viral hepatitis, chronic pancreatitis
o immune response may be maladaptive and may promote tumorigenesis
o chronic inflammation may cause fixation of maladaptive mechanisms
o ex. COX-2 is induced by inflammatory stimuli and is increased in colon cancers and other tumors

65

inflamm. bowel disease

colorectal carcinoma

66

chronic pancreatitis

- seen with alchoholics
- pancreatic carcinoma

67

Barret's esophagus

esophageal carcinoma

68

sjogren syndrome/hashimoto thyroiditis

MALT lymphoma

69

hetpatitis

hetpatocellular carcinoma

70

mononucleosis

B-cell non-Hodgkin lymphoma and Hodgkin lymphoma
- b/c of EBV

71

AIDS

Non-Hodgkin lymphoma, squamous cell carcinoma, Kaposi sarcoma

- Because of Human immunodeficiency virus, human herpesvirus type 8

72

mid UV radiation

Malignant Melanoma
Squamous Cell Carcinoma
Basal Cell Carcinoma

73

ionizing radiation

Thyroid Carcinoma-Chernobyl
Leukemia - Hiroshima

74

cig. smoking

lung carcinoma

75

Helicobeter pylorii

gatric carcinoma

76

ethanol/cirrhosis

hepatocellular carcinoma

77

HPV 16,18

carcinoma uterine/cervix

78

30 y/o woman with atypical endometrial hyperplasia

endometrial adenocarcinoma

79

dysplastic bronchial mucosa

bronchogenic carcinoma

80

leukoplakia of oral cavity

squamous cell carcinoma

81

TGFA

prooncogene -
overexpression of TGFalpha
Astrocytomas, hepatocellular carcinomas

82

HGF

protooncogene
ovexpression of HGF
Thyroid cancer

83

ERBB1 (EGFR)

overexpression of EGF-receptor family (protooncogene)

Squamous cell carcinoma of lung, gliomas

84

RET

protooncogene
point mutation causes leukemia

85

KRAS/HRAS/NRAS

PO
pointmutation affects GTP-binding

*** dyrsregulation of RAS/RAF/MAP pathway is linked with melanomas***

KRAS:Colon, lung, and pancreatic tumors
HRAS: Bladder and kidney tumors
NRAS: Melanomas, hematologic malignancies

86

ABL

PO
translocation causes chronic myeloid leukemia, acute lymphoblastic leukemia

87

BRAF

PO involved in RAS signal transduction
point mutation causes melanomas

88

C-MYC

PO, transcriptional activator

translocation causes burkitt's lymphoma

89

N-MYC

PO, transcriptional activator

amplification causes
Neuroblastoma, small-cell carcinoma of lung

90

L-MYC

PO, txn activator
amplification causes small-cell carcinoma of the lung

91

Cyclin D

PO, translocation causes mantle cell lymphoma

amplification causes breast and esophageal cancers

92

Cyclin E

PO

overexpression causes breast cancers

93

CDK4

PO - amplification of point mutation

Forms a complex with cyclin D that phosphorylates RB, allowing the cell to progress through the G 1 restriction point.

glioblastoma, melanoma and sarcomas

94

RAS mechanism

point mutation of the RAS family genes I sthe single most common abnormality of proto-oncogenes in human tumors
• Oncogene
• Ras plays role in signaling cascade, resulting in mitogenesis
• it is activated by growth factor binding at PM
• RAS proteins flip back forth b/w excited and quiescent state
o recycling occurs through nucleotide exchange (GDP to GTP) which activates protein
• Catalyzed by guanine nucleotide releasing proteins
o GTP hydrolysis → GDP to inactivate
• Catalysed GTPase activity via GTPase-activating proteins (GAPs): act as “brakes”
• inactived RAS = RAS + GDP
• Activated RAS = RAS + GTP
• Activated RAS stimulates mitogen-activated protein (MAP)

95

amatinib mesylate

drug that inhibits BCR-ABL kinase

96

mechanism of MYC

• oncogene
• MYC interacts with components of DNA-replication machinery and plays a role in selection of origins of replication.
• overexpression may drive activation of more origins than needed for normal cell division,
• MYC can act to reprogram somatic cells into pluripotent stem cells
• Dysregulation of MYC resulting from translocation of gene results in Burkitt Lymphoma – B cell tumor

97

Cyclins and CDK's

• CDK-cyclin complexes phosphorylate crucial target proteins that drive the cell through the cell cycle
• mutations result in increased activity of cyclins and CDKs favoring proliferation
• cyclincs bind CDKs and intiate cell proliferation

98

what are CDKI's?

• CIP/WAF family: p21, p27, p57
• INK4 family: p16, p16, p18
• expression of these inhibitors is down-regulated by mitogenic signaling pathways thus promoting the progression of cell cycle

99

CDK2

Forms a complex with cyclin E in late G 1, which is involved in G 1/S transition. Forms a complex with cyclin A at the S phase that facilitates G 2/M transition.

100

CDK1

Forms a complex with cyclin B that facilitates G 2/M transition.

101

p21, p27

Block the cell cycle by binding to cyclin-CDK complexes; p21 is induced by the tumor suppressor p53; p27 responds to growth suppressors such as TGF-β.

102

INK4/ARF family

p16/INK4a binds to cyclin D–CDK4 and promotes the inhibitory effects of RB; p14/ARF increases p53 levels by inhibiting MDM2 activity.

103

p53 main fn.

Tumor suppressor gene altered in the majority of cancers; causes cell cycle arrest and apoptosis. Acts mainly through p21 to cause cell cycle arrest. Causes apoptosis by inducing the transcription of pro-apoptotic genes such as BAX. Levels of p53 are negatively regulated by MDM2 through a feedback loop. p53 is required for the G 1/S checkpoint and is a main component of the G 2/M checkpoint.

104

TGF-beta receptor

TS
Growth inhibition
somatic mutations: Carcinomas of colon

105

E-cadherin

TS
FN; cell adhesion
SM: carcinoma of stomach
IM: familal gastric cancer

106

NF1

TS
FN: Inhibition of RAS signal transduction and of p21 cell cycle inhibitor
SM: neuroblastomas
IM: Neurofibromatosis type 1 and sarcomas, optic nerve gliomas

107

NF2

TS
fn: cytoskeletal stability
SM: Schwannomas and meningiomas
IM: Neurofibromastosis type 2, acoustic schwannomas, and meningiomas

108

APC/β-catenin

TS
fn: inhibition of signal transdution
SM: Carcinomas of stomach, colon, pancreas; melanoma
IM: Familial adenomatous polyposis coli/colon cancer

109

PTEN

TS:
Fn: PI1 kinase signal transduction
SM: endometrial and prostate cancers
IM: Cowden syndrome

110

SMAD2 SMAD4

TS
Fn:TGF-β signal transduction
SM: colon, pancreas tumors

111

RB1

TS
Fn: regulation of cell cycle
SM: Retinoblastoma; osteosarcoma carcinomas of breast, colon, lung
IM: Retinoblastomas, osteosarcoma

112

p53

TS
Fn: Cell cycle arrest and apoptosis in response to DNA damage
SM; most human cancers
IM: Li-Fraumeni syndrome; multiple carcinomas and sarcomas

113

WT1

TS
Fn: nuclear txn
SM/IM: Wilm's tumor

114

p16/INK4a

TS
fn: Regulation of cell cycle by inhibition of cyclin-dependent kinases
SM: Pancreatic, breast, and esophageal cancers
IM:Malignant melanoma

115

BRCA1/BRCA2

fn: dna repair
IM: Carcinomas of female breast and ovary; carcinomas of male breast

116

two hip hypothesis

• two mutations are required to eliminate tumor suppressor genes
• in familial cases: one gene is inherited, the other spontaneously mutates
• in sporadic cases: both genes must mutate
• Thus heterozygosity of the RB gene does not affect cell behavior

loss of heterozygosity: when the cell loses both of its normal alleles, it results in loss of the gene

117

mechanism of RB

• exists in an active hypophosphorylated state in quiescent cells and in an inactive hyperphosphorylated state in G1/S transition (most important checkpoint)
- if RB is hypophos. then it remains bound to E2F, and E2F cannot signal txn
(RB can be hypophos. via Ggrowth inhibitors stimulated CDKI's)
- RB is hyperphsophorylated via Growth factors (EGF, PDGF) stimulated cyclins D/E, resulting in release of E2F and transcriptional activity

*note HPV is known to inactivate RB protein

118

Li-Fraumeni syndrome

mutation in p53: results in increases in malignant tumors – sarcomas, breast cancer, leukemia, brain tumors, carcinomas of arenal cortex

119

MDM2/MDMX

stimulate the degredation of p53, and are often overexpressed in malignancies where p53 is not mutated

120

APC/β Catenin Pathway:

• adenomatous polyposis coli genes represent tumor suppressors that down-regulate growth promotic receptors.
• germline mutations result in thousands of adenomatous polyps in colon during teens to 20’s
• usually polyps will undergo transformation giving rise to colonic tumors
• APC dowregulates B-catenin in the absence of WNT signaling, preventing Beta catenin to accumulate in the cytoplasm
• WNT triggered, inhibits APC, allowing B-Catenin build up, resulting in increase in c-myc and cyclinD.
• cells with loss of APC behave as if under continuous WNT signaling
• Beta-Catenin binds E-Cadherin (cell surface protein that maintains intercellular adhesiveness) – loss of cellular contact allows B-Catenin to stimulate proliferation = contact inhibited

121

contact inhibition

• Beta-Catenin binds E-Cadherin (cell surface protein that maintains intercellular adhesiveness) – loss of cellular contact allows B-Catenin to stimulate proliferation

122

anoikis

loss of adhesion to BM, can trigger apoptosis

123

BCL2

ovexpression leads to tumors due to loss of apoptosis

124

angiogenesis

• bFGF and VEGF

125

bavacizumab

anti-VEGF Ab used for treatment

126

MMPs

** overexpression of MMPs has been implicated in many tumors

proteases that have been implicated in tumor invasion. MMP’s regulate tumor invasion not only by remodeling insoluble compnents of BM but also by releasing ECM-sequestered growth factors
o breakdown products of collagen have a chemotactic and angiogeneic and growth promoting effects
o MMP9 = gelatinase that cleaves collagen type IV

127

CD44

adhesion molecule: expressed on normal T lymph. is used by tumors to migrate to selective sites in lymphoid tissue
o overexpression of CD44 may favor metastatic spread

128

CXCR4 and CCR7

chemokines that are expressed --> in some breast cancers --> allow for metastasis to lymph nodes

129

Hereditary nonpolyposis colon cancer syndrome:

Hereditary nonpolyposis colon cancer syndrome:
• results from defects in genes involvedin DNA mistmatch repair – results in creation of microsatellites, causing microsatellite instability
• familial carcinomas of the colon

130

xeroderma pigmentosum

• defective DNA excision repair
• UV radiation causes crosslinking of pyrimidine residues, and lacks excision repair
• increased development of cancers of the skin, especially after exposure to sunlight

131

bloom syndrome

• defect in DNA repair by homologous recombination

132

BRCA1/BRCA2

• breast cancers
• cells lacking these genes have been shown to associate with a variety of proteins involved in homologous recombination repair pathway

133

warburg effect

• cancer cells shift to aerobic glycolysis
• aerobic glycolysis allows tumors to need less O2 supplied by blood
• HIF1alpha downregulates genes involved in ox phos
• decreased demand by tumor cells increases the O2 supply, allowing for increased number of tumor cells that can be supported by the vasculature
• halting of breakdown from glucose to pyruvate allows these carbons to be shunted to anabolic pathway and thus used for building blocks for cell division
• LKB1: tumor suppressor gene that halts anabolic metabolism

134

Burkitt Lymphoma

c-MYC
overexpression of proto-oncogene due to translocation
o MYC is translocated to IGH sequence t(8:14)(q24;q32) and thus loses its regulatory sequence
o IGH is highly expressed in B cell precursors

135

BCR-ABL

• Philidelphia chromosome:
o fusion of genes from 9 and 22 forming BCR-ABL gene
o characteristic of CML and acute lymphoblastic leukemias

136

ERBB2

protooncogene
gene amplification often leading to breast cancer

137

VHL

tumor suppresor - silenced in renal cell carcinomas

138

miRNAS

• mediate post transcriptional gene silencing through RNA-induced silencing complex
• by negatively regulating BCL2 (anti-apoptotic protein), miRNAs behave as tumor suppressor genes

139

CYP1A1

• ex. cigarette smoke: metabolized by the P-450 gene, CYP1A1 – smokers with this genotype are more susceptible to lung cancer

140

HTLV-1

Human T cell Leukemia Virus Type 1: (HTLV-1) -
• causes a form of T-cell leukemia/lymphoma (seen in Japan and carribean)
• affects CD4+ T cells
• contains protein tax that stimulates txn of viral mRNA by acting on 5’ terminal repeat: it inactivates inhibitor p16/INK4a and enhances cyclin D activation. tax also activates NF-kb
• HTLV-1 causes expansion of nonmalignant polyclonal cell population through stimulatory effects of Tax – the proliferating T cells are at increased risk of mutations and genomic instability induced by Tax, allowing mutations to accumulate and eventually a monoclonal neoplastic T-cell population emerges

141

HPV

– type 16 and 18 – cause squamous cell carcinoma of cervix and anogenital region
• cells in which viral genome is integrated have moregenomic instability, integration interrupts the viral DNA within the E1/E2 open reading frame, leadig to loss of E2 viral repressor, and overexpression E6/E7 oncoproteins.

142

E7

binds to the Rb protein and displaces E2F txn factor – promoting progression through cell cycle. E7 also inactivates CDKI’s p21 and p27.

143

E6

has higher affinity for p53 and blocks p53, thus disabling apoptosis

144

EBV

• Burkitt-Lymphoma: B-cell lymphoma, Hodgkin lymphoma, nasopharyngeal and gastric carcinomas, rare forms or T cell lymphomas and NK lymphomas
o except for nasopharyngeal carcinoma, all others are B-cell tumors
• EBV infects B lymphocytes using the CD21 receptor to attach and infect B cells
• LMP-1: latent membrane protein 1, acts as an oncogene and acts on CD40 receptor, activating the NF-kb pathway and JAK/STAT signaling, causing B-cell survival and proliferation
o also activates BCL2, prevening apoptosis
• Burkitt lymphoma: neoplasm of B lympohcytes that is most common childhood tumor in central Africa and New Guinea
o in regions of world where Burkitts is endemic, concomitatnt infections such as malaria impaire immune competence, allowing sustained B cell proliferation.

145

Hep B and Hep C

• close association with HBV infection and liver cancer – Hepatocelluar carcinomas
• dominant effect seems to be immunologically mediated chronic inflammation with hepatocyte death leading to regeneration and genomic damage
• chronic viral infection leads to compensatory proliferation of hepatocytes
• Activation of the NF-kB pathway w/in hepatocytes blocks apoptosis, allowing dividing hepatocytes to incur genotoxic stress and accumulate mutations

146

H. pylori

• bacterium that causes gastric adenocarcinomas and gastric lymphomas
o MALTomas = mucous associated lymphoid tissue
• involves increased epithelial cell proliferation in a background of chronic gastric inflammation (similar to viral hep)

147

tumor ags recognized by CD8 T cells?

DNA viruses: HPV and EBV

148

antitumor effector cells?

• CTL’s are effective against virus-associated neoplasms: important against HPV, EBC

• NK cells: capable of destroying tumor cells without prior sensitization – thus may provide first line defense
o tumors that don’t express MHC I class Ags cannot be recognized by T cells, these may however trigger NK cells which are normally inhibited by recognition of normal class I molecules

149

AIDS cancers

non-hodgking lymphoma (50%), primary CNS lymphoma, Kaposi sarcoma, cervical neoplasia

150

cushing syndrome

Cushing Syndrome: ** very common**
• results from small-cell carcinoma of lung
• ACTH is secreted in xs – see elevated corticotropin levels

151

hypercalcemia

Hypercalcemia: ** very common**
• seen with squamous cell carcinomas of lung
• Release of PTH or PTH related proteins: TGFalpha, TNF, IL-1
• may also be seen with osteolytic cancers such as osteosarcomas, multiple myeloma, metastatic bone lesions

152

SIADH

Syndrome of Inappropriate ADH secretion:
• seen with small cell carcinoma of lung

153

Nonbacterial thrombotic endocarditis

Nonbacterial thrombotic endocarditis
• seen with advanced cancers – i.e. mucin secreting adenocaricnomas
• results in hypercoagulability

154

acanthosis nigricans

gray black patches of hyperkeratosis on the skin
• gastric carcinoma, lung carcinoma, uterine carcinoma
• immunological causes; results in secretion of EGF

155

hypertrophic osteoarthropathy

• seen in 1-10% of patients with bronchogenic carcinomas

characterized by
o periosteal new bone formation, at distal ends of long bones, fingers
o arthritis of adjacent joints
o clubbing of digits

156

grading v. staging

Grading: based on degree of differentiation, and in some cancers the number of mitoses or architectural features
– Typically established by the pathologist
– How differentiated is the tumor? Other factors affecting or mitigating?

Staging: based on size of primary lesion, extent of spread to reginal lymph nodes, presence or absence of blood-borne metastases
– Typically established by the oncologist (although ‘contributed to [depending on the malignancy] by the pathologist’
– How widely spread is the cancer? TNM factors.
– T= tumor, N=Lymph node, M=Metastases

157

prevalence vs. incidence

Prevalence: Total cases in defined population on a specified date (e.g., Jan 1, 2007); Prevalence represents both new and all pre-existing cases alive on a certain date enumerated by one of these three possible methods of expression:
An absolute number (e.g., total cases in US)
Expressed as % population (Total cases in population as %)
Number cases/100,000 population at the specified date

Incidence: New cases diagnosed during specified time (usually a year) for given population (100,000 unit often used)
Incidence reflects only new cases during a defined time.
# new cases/100,000 population/year

158

patients with multiple myeloma

gG kappa is seen most commonly in patients with multiple myeloma on electrophoresis

159

TdT

primitive B cell marker

160

Beta2 microglobulin

primitive B cell marker
- lymphoid malignancies: B-cell chronic lymphocytic leukemia, non-Hodgkin Leukemia, multiple myeloma

161

PSA vs. Her2

PSA is organ-specific but not cancer-specific, whereas HER2/ neu is cancer-specific but not tissue-specific and is found to be increased in breast cancers, as well as lung and other epithelial cell tumors.

162

CEA

carcinoembryonic Ag
- tumor marker for GI cancer: but also elevated in adenocarcinomas of breast, lung, liver cancers
- used to only be for colon cancer

163

CA-19-9

gastric cancer, pancreatic cancer, colon cancer

164

CA 125

marker for ovraian cancers

165

Cytokeratin 19 fragment (CYFRA 21-1)

breast cancer and squamous cell carcinoma of lung

166

HcG

elevated in trophoblastic tumors and choriocarcinomas of females

elvated in seminomatous testicular tumors in males

167

AFP

alpha feto protein
- hepatocellular carcinoma and germ cell tumors of testis

168

PTH-RP

Parathyroid Hormone-Related Peptide
Plasma concentrations of parathyroid hormone-related peptide (PTH-RP) are elevated in the majority of patients with cancer-associated hypercalcemia.

secreted by tumors associated with hypercalcemia.

169

calcitonin

medullary carcinoma of thryoid

170

metanephrine

pheochromocytoma

171

PSA

prostate cancer

172

CA-15-3

breast cancer

173

CA72-4

gstric carcinoma

174

Her2-/neu

breast cancer

175

p53, APC, RAS mutants in stool and serum

colon cancer

176

p53 and RAS mutants in stool and serum

pancreatic cancer

177

p53 and RAS mutants in sputum and serum

lung cancer

178

p53 mutants in urine

bladder cancer