IHC Markers Flashcards by Leon Foster

PAX8 is

PAired boX 8 - A DNA transcription factor.

Highly specific for primary ovarian carcinoma - except mucinous + others.

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WT1 is

Tumor suppressor gene that inhibits transcription of growth-promoting genes
+ve Serous carcinoma, Endocervical glands, Ovarian mucinous,
-ve Clear cell carcinoma. Granulosa Cell Tumours, Sex Cord Stromal Tumour. SCC - Hypercalcaemic Type. Renal Cancer

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CK20

Type I cytokeratin that is a major cellular protein of goblet cells and mature enterocytes.
To ID range of adenocarcinoma that normally express CK20.
E.g. CRC, Transitional cell carcinoma, Merkel Cell carcinoma.
Absent in Lung, Prostate and non-mucinoous OVarian. Often in combo with CK 7 to differentiate.

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CK7

Is a type II keratin. Expressed in simple epithelia that line the cavities of internal organs, lymphatics and blood vessels.
Can be used by IHC to distinguish Ovarian and transitional cell carcinoma from colonic and prostate Ca.

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CDX2

It is a marker of gastrointestinal differentiation.
+ve staining in - CRC (86-100%),

Endometrial lesions with squamous differentiation, esp morular type differentiation.
Also +ve in mucinous adenocarcinoma of ovary, cervix and lung also signet cell adenocarcinoma.
Small intestine carcinoma, stomach adenocarcinoma, Neuroendocrine tumours,

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Vimentin

Type III intermediate filament protein. Major cytoskeletal component of mesenchymal cells.
+ve staining in:
- Endometrial carcinoma, most sarcomas or other mesenchymal tumours. Mucinous carcinoma of uterus - not of cervix.
Distinguishing endocervical and endometrial adenocarcinoma.

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p53

p53 helps regulate the cell cycle, apoptosic and genetic stability.
- activates DNA repair
- can arrest growth
- can initiate apoptosis
Can distinguigh uterine serous from ovarian serous. STIC lesions.
-ve in SCC cervix.

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NAPSA

NAPSA gene encodes a proteinase - Napsin-A. Can differentiate adenocarcinomas from other forms of Lung Ca. Also Ovarian clear cell carcinoma + Pulmonary and renal cell carcinoma.

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HNF1B

HNF1 homeobox B (hepatocyte nuclear factor 1 homeobox B), also known as HNF1B or transcription factor 2 (TCF2).
Positive in CCC, also reported in gastric-type
and mesonephric carcinomas

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AMACR

Alpha Methyl Acyl Coenzyme A Racemase;
AKA P504S.

Useful in mesonephric carcinoma (cervix) and clear cell carcinoma

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GCDFP15

Used to differentiate Br Mets +ve from ovarian primary -ve.

Prolactin-inducible protein Gross Cystic Disease Fluid Protein 15 (GCDFP-15).
+ Serous glands. Also found in amniotic and seminal fluid.

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Mmglb

Mammaglobin is limited to the adult mammary gland. +ve Br Ca

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HER2/neu

Member of the human epidermal growth factor receptor (HER/EGFR/ERBB2). cytoplasmic tyrosine kinase that becomes constitutionally active.
Br Ca - 15-20%, 7 - 34% gastric cancer. Uterine Serous ~ 40% +, 35 - 45% of pancreatic Ca, Ovarian epithelial 11-66%.

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Fascin

Microfilament protein. +ve in carcinoma of Breast, colon, lung, ovary, pancreas, skin

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SMAD4

AKA MADH4 or DPC4

Not +ve in mucinous ovarian but are in 10-20% of CRC, including appendiceal, including mucinous carcinoma peritonei

Associated primarily with Ca pancreatic,
mutated in
~ 55% of pancreatic ductal adenocarcinoma,
25% of extrahepatic cholangiocarcinoma,
34% of ampullary carcinoma and

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SATB2

Highly expressed in epithelium of the lower GIT. Narrow profile in malignancies, including colorectal/appendiceal adenocarcinomas, tumors of osteoblastic differentiation, and renal/urothelial carcinomas. Used to distinguish primary ovarian mucinous adenocarcinomas from colorectal metastases.

TTF1

TTF1 - highly specific marker for primary lung adenocarcinomas (100% specificity). Can be used in identifying the primary site in small cell neuroendocrine tumours of the cervix.

NSE (Neuron Specific Enolase)

+ve in neuroendocrine cancers of the cervix.

Cytoplasmic enzyme expressed by neuroendocrine cells and tumors. Not specific for neuroendocrine tumours.

Synaptophysin

+ve small cell neuroendocrine cervix Ca

CGA (Chromogranin A)

well differentiated vs. poorly differentiated tumor. Useful in Cervix Neuroendocrine.

CD56

+ve in
neuroendocrine tumours.
Small cell neuroendocrine tumours of the cervix.

Alfa 1- antitripsin

IHC stain +ve for Endodermal teratoma, MMMT, Yolk sac tumour, Small Cell carcinoma - hypercalcaemic type

PAS IHC?

PAS (Periodic Acid-Schiff) 
\+ve in Adenocarcinoma of 
- mucinous tumours
- small cell carcinoma of the ovary, 
- clear cell tumours, 
 - granular cell tumour, 
 and 
- paget disease of breast

laminin IHC

Basement membrane type IV collagen.

Useful to detect microinvasion in VIN or CIN. Also +ve in small cell carcinoma of ovary.

E-Cadherin

E-cadherin is a transmembrane protein involved in cellular adhesion and polarity maintenance and is expressed in almost all epithelial cells. Most carcinoma have strong diffuse staining. Invasive and DCIS > 90%. SCC oral cavity (40%) Lung adenocarcinoma (60%) Lung SCC (40%) Gynecologic serous carcinoma (100%) Colorectal carcinoma (85%) HCC - 60%.

S100

+ve staining in Melanoma, Neuroendocrine tumours and sex cord stromal tumours

CD56

+ve in: small cell carcinoma of the cervix Neuroendocrine carcinomas Ovarian fibroma, fibrothecoma, leiomyoma

P16

Tumour suppressor protein. Considered to be a surrogate marker for HPV infection. +ve in: HPV related anogenital precurors e.g cervical SIL, AIS, usual VIN, VAIN, undifferentiated PeIN SCC - anogenital, oropharyngeal, some esophageal, some bladder) Endocervical adenocarcinoma Uterine serous carcinoma High grade serous carcinoma of Müllerian origin in general Some malignant mixed Müllerian tumors and undifferentiated carcinoma

CEA

CEA / CD66 ``` +ve Adeno Ca lung (97% specific) CRC (elevated in 72-97%) HCC Pancreatic adenocarcinoma ```

SATB2

Present in 85% of CRC | SATB2 + CK20 IDs >95% of all CRC

SMAD4 / DPC4 / MADH4

Tumour suppressor gene 20% of CRC Carcinoma in situ in mucinous cystic neoplasms

CD10

+ve in ESS. differentiates ESS from smooth muscle tumours. +ve in Endometriosis Mesonephric remnants and tumors are CD10+. metastatic renal cell carcinoma CD10+ve from primary clear cell carcinoma CD10-ve

PTEN

Phosphatase and Tensin Analogue - Tumour suppressor gene that is commonly lost in Ca. Astd with Cowden syndrome, Endometrial carcinoma

Calretinen

sex cord stromal tumors (50-100%, including inhibin negative tumors, cervical mesonephric adenocarcinoma (88%) Colonic medullary carcinoma (73%) Colorectal adenocarcinoma granular cell tumor

SF1

S for part of the Steroid receptor family. Found in Granulosa and Theca cells of the ovary. Also sertoli lleydig cells in males. For Dx of gonadotroph adenomas +ve staining in sex cord stromal tumours of the ovary + some pituitary stromal tumours

Inhibin

+ve staining in Sex cord stromal tumours, including Sertoli cell tumors, adrenocortical tumors, placental and gestational trophoblastic lesions, Granular cell tumours of gallbladder and extraheptic bile ducts. Some carcinomas.

FOXL2

FOXL2 immunostain is a sensitive (80%) and specific (99%) marker for sex cord stromal tumors - superior to α-inhibin and calretinin and is positive in almost all SCST (98%) with FOXL2 mutation and a large number of those without mutation (67%); majority of adult GCTs (93%) are positive with FOXL2 stain and the immunostain cannot differentiate adult GCT from other SCSTs

CD99

Also known as: MIC2, O13, T cell surface glycoprotein E2 is a cell surface glycoprotein. +ve in lots. MOST ovarian sex cord-stromal tumours, spindle cell epithelioma of the vagina, Uterine tumours resembling ovarian sex cord-stromal tumours. In Gyn Ca: Cervicovaginal myofibroblastoma, Endometrial stromal sarcoma with sex cord differentiation, GIST,

SMARCA4 (BRG1)

Small Cell Carcinoma of the Ovary Hypercalcaemic Type (SCCHCT)