Laboratory Diagnosis of Cancer

1. excision or biopsy

2. fine needle aspiration

3. cytologic (pap) smears

4. immunohistochemistry

5. flow cytometry

histologic and cytologic methods for diagnosis of cancer

fine needle aspiration

most commonly used for the assessment of readily palpable lesions in sites: breast, thyroid, lymph nodes

fine needle aspiration

less invasive, extremely reliable and useful

cytologic (pap) smears

widely used to screen for carcinoma of the cervix (often at in situ stage)

cytologic (pap) smears

used for suspected malignancy of

• endometrial carcinoma

• bronchogenic carcinoma

• bladder and prostatic tumors

• gastric carcinomas

cytologic (pap) smears

identification of tumor cells in

• abdominal

• pleural

• joint

• cerebrospinal fluid

1. keratin

2. EMA—epithelial membrane antigen

3. CEA—carcinoembryonic antigen

4. TTF-1—thyroid transcription factor

5. PSA—prostate specific antigen

epithelial tumor markers

1. actin

2. vimentin

3. desmin

4. glial fibrillary acidic protein (GFAP)

5. neurofilament (NF)

6. S100 protein

intermediate filament markers

1. neuron specific enolase (NSE)

2. chromogranin

3. synaptophysin

neuroendocrine markers

1. human chorionic gonadotropin (hCG)

2. alpha-fetoprotein (AFP)

3. placental-like alkaline phosphatase (PLAP)

germ cell tumor markers

1. myogenic tumors

2. fibrohistiocytic tumors

3. vascular tumors

4. melanomas

5. lymphomas

mesenchymal tumor markers

keratin

highly sensitive marker for epithelial cells

cytokeratin 7 (CK7)

marker for lungs EC

cytokeratin 7 (CK7)

marker for breast EC

cytokeratin 7 (CK7)

marker for uterus EC

cytokeratin 7 (CK7)

marker for ovaries EC

• lungs

• breast

• uterus

• ovaries

cytokeratin 7

cytokeratin 20 (CK20)

marker for colon and stomach EC

• colon

• stomach

cytokeratin 20

epithelial membrane antigen (EMA)

marker for adenocarcinoma of the breast

epithelial membrane antigen (EMA)

marker for adenocarcinoma of the lungs

epithelial membrane antigen (EMA)

marker for adenocarcinoma of the kidneys

adenocarcinoma of

• breast

• lung

• kidneys

epithelial membrane antigen (EMA)

carcinoembryonic antigen (CEA)

oncofetal Ag present in carcinomas of the GI tract, pancreas, lung, breast, and ovary

• GI tract

• pancreas

• lungs

• breast

• ovary

carcinoembryonic antigen (CEA)

adenocarcinoma

CEA-positive

mesothelioma

CEA-negative

• thyroid

• lung

• neuroendocrine tumors

thyroid transcription factor (TTF-1)

prostatic adenocarcinoma

prostate specific antigen (PSA)

actin

contractile protein present in muscle

muscle differentiation

actin—sensitive marker for

vimentin

present in normal mesenchymal cells & their neoplastic counterparts

melanomas and schwannomas

always stain positive for vimentin

desmin

intermediate filament expressed by smooth and striated muscles

myogenic tumors

• leiomyoma (smooth muscle tumor)

• rhabdomyosarcoma (skeletal muscle tumor)

desmin is highly sensitive for

glial fibrillary acidic protein (GFAP)

intermediate filament protein expressed by CNS glial cell—astrocytes

astrocytoma

glial fibrillary acidic protein (GFAP) most widely used to confirm

neurofilament (NF)

expressed in cells of neural origin: neuronal processes, peripheral nerves, sympathetic ganglia, adrenal medulla, and neuroendocrine cells

cells of neural origin

• neuronal processes

• peripheral nerves

• sympathetic ganglia

• adrenal medulla

• neuroendocrine cells

neurofilament expressed in

neuronal or neuroendocrine differentiation

neurofilament (NF) is positive for

S100 protein

expressed in CNS glial cells, melanocytes, histiocytes, chondrocytes, skeletal & cardiac muscles

• CNS glial cells

• melanocytes

• histiocytes

• chondrocytes

• skeletal & cardiac muscles

S100 protein expressed in

neuron-specific enolase (NSE)

isoenzyme marker, provides strong evidence of neural or neuroendocrine differentiation

neural or neuroendocrine differentiation

neuron-specific enolase (NSE) is a strong evidence of

neuroendocrine differentiation

chromogranin is a marker for

chromogranin

marker for neuroendocrine differentiation found in the neural secretory granules

neuroendocrine carcinoma

(+) chromogranin

(+) keratin

paraganglioma

(+) chromogranin

(-) keratin

synaptophysin

transmembrane protein associated w/ presynaptic vesicles of neurons, also seen in normal neurons & neuroendocrine cells

choriocarcinoma

human chorionic gonadotropin is a marker for

human chorionic gonadotropin

choriocarcinoma marker synthesized by placental syncytiotrophoblasts

• endodermal sinus tumors

• embryonal carcinoma

• teratoma

• hepatocellular carcinoma

alpha-fetoprotein (AFP) is a marker for

alpha-fetoprotein (AFP)

synthesized by normal liver hepatocytes—marker for:

• endodermal sinus tumors

• embryonal carcinoma

• teratoma

• hepatocellular carcinoma

germ cell tumors (germinomas)

placental-like alkaline phosphatase (PLAP)

placental-like alkaline phosphatase (PLAP)

marker for germ cell tumors (germinomas) produced by placental syncytiotrophoblasts in late pregnancy

skeletal muscle

myogenic tumors origin

• muscle-specific actin & desmin

• Myo-D1

• myoglobin

• myogenin

myogenic tumors positive for

• CD68

• FAM 56

• alpha-1-antitrypsin

• alpha-1-chymotrypsin

fibrohistiocytic tumors positive for

vascular tumors

angiosarcomas

• Factor VII-related ag

• CD31

• Ulex europaeus 1 (UEA)

vascular tumors positive for

melanosome (HMB-45)

a highly sensitive & specific marker for melanomas

melan-A (MART-1)

encodes for melanoma-specific ag

leukocyte common antigen (LCA) or CD45

best screening marker for lymphoma

• CD3

• CD4

• CD8

tumor marker for T-cell lymphoma

• CD19

• CD20

• CD23

tumor marker for B-cell lymphoma