IHC Flashcards
p53 is commonly mutated in?
Typically expressed strongly and diffusely by High Grade Serous Carcinoma
p16 is mutated in and what does it cause?
Surrogate marker for HPV infection and HPV associated Ca Elevated levels in - Ca Cervix - CIN 2/3 - High grade serous carcinoma
Tumour suppressor gene. slowing progression from G1 to S phase.
Different Ca have different types of p16 expression.
Cancers that overexpress p16 are usually caused by HPV, whereas cancers in which p16 is downregulated will usually have other causes.
WT-1
+ve
high grade serous
Sex cord stromal tumours
-ve
Clear cell carcinoma (up to20% +ve)
Endometrial glands
Ovarian mucinous carcinoma
Endometrial adenocarcinoma (up to ~20% may be +ve - Meta analysis https://pubmed.ncbi.nlm.nih.gov/32859123)
Tumour suppressor gene. Protein is transcriptional regularo that inhibits transcription of growth promoting genes.
CEA
Usually considered an epithelial marker with strong staining in adenocarcinoma.
\+ve in Cervical adenocarcinoma Cervix SCC Endometrial adenocarcinoma (50%) Mucinous ovarian (92%) Paget's all sites Choriocarcinoma
Plus lots of others:
Bile duct ,bladder, breast, CRC (almost all) gastric, hepatic Ca. Neuroendocrine, pancreatic, thymoma, thyroid
May play a roles in metastasis of Ca cells
Normally detected in glycocalyx (peri-cellular matrix) of foetal eipithelial cells
CK7 + / CK 20 +
CK 7+ / CK 20+
Primary mucinous tumour of ovary Bile duct Ca Gastric Adeno Pancreatic Ca Pulmonary Invasive mucinous adenocarcinoma Sinonasal adenocactinoma Small intenstinal Adenocarcinoma Urothelial carcinoma
CK 7+ / CK 20 -
Cervix SCC and Adenocarcinoma
Endometrial Adenocarcinoma
Ovarian Ca - including endometriod, clear cell, serous, seromucinous
Breast oesophagus Gastric Bile duct Lung acinar adeno Mesothelioma Pancreatic adeno Renal cell Salivery glan Thyroid urothelial Ca
CK 7- CK 20+
Colorectal Ca
Merkel cell carcinoma (88%)
CK 7- / CK 20 -
germ cell tumour
Renal cell carcinoma (clear cell type)
SCC - except cervix ca.
CK 7
+ve in adenocarcinoma of endometrium, cervix, ovary + lung, breast, thyroid, salivary gland,
-ve in CRC, merkel cell carcinoma, HCC, adrenocortical tumors and SCC
AKA keratin 7, KRT 7, K7
ER
Oestrogen Receptor Distinguishes Endocervical (ER-ve) with Endometrial (ER+ve) adenocarcinoma \+ve in 75% of Endometrial adenocarcinoma \+ve in Ovarian Serous, mucinous and endometrioid adenocarcinoma and ovarian transitional cell carcinoma,
ALso Br
-ve Endocervical Ca, Ovarian clear cell Ca.
GATA 3
Breast marker. \+ve in metastatic Breast and Urothelial \+ve in Lobular carcinoma of the breast \+ve in Mesonephric cervix SCC skin + from SCC lung -ve
HIK1083
Diagnostic of Adenoma malignum, Now called adenocarcinoma HPV independent gastric type (that astd with Peutz-Jegher)
Also - Detect gastric metastasis
Cervix: Diagnostic of adenoma malignum
Ki-67
marker of cell proliferation.
Nuclear stain
Prognostic in Br Ca and used for prognosis of relative responsiveness, resistance to chemo or endocrine therapy and biomarker of treatment efficacy (high % reflects worse prognosis)
P40
Primarily for differentiating lung SCC from Adenocarcinoma.
I.e. Squamous cells from adeno.
Also used in Cervix.
MUC 6
+ve stain in Breast Cancer and gastric Ca.
P63
Cervix: epithelioid trophoblastic tumor, lymphoepithelioma-like carcinoma, placental site nodule, spindle cell carcinoma
PTEN
What does it do.
How often is it mutated?
Which congenital syndrome is it associated with ?
How often mutated in Endometrial and OVarian Ca?
Phosphatase and tensin homolog(PTEN) is aproteinthat, in humans, is encoded by thePTENgene.Mutations of this gene are a step in the development of manycancers.
Also called Mutated in Multiple Advanced Cancers 1 (MMAC1)
PTENacts as atumor suppressor genethrough the action of itsphosphataseprotein product. This phosphatase is involved in the regulation of thecell cycle, preventing cells from growing and dividing too rapidly.It is a target of many anticancer drugs.
PTEN is one of the most commonly losttumour suppressorsin human cancer; in fact, up to 70% of men with prostate cancer are estimated to have lost a copy of thePTENgene at the time of diagnosis.
During tumor development, mutations and deletions of PTEN occur that inactivate its enzymatic activity leading to increased cell proliferation and reduced cell death. Frequent genetic inactivation of PTEN occurs inglioblastoma,endometrial cancer, andprostate cancer; and reduced expression is found in many other tumor types such as lung and breast cancer. Furthermore,PTENmutation also causes a variety of inherited predispositions to cancer.
Researchers have identified more than 70mutationsin thePTENgene in people withCowden syndrome
PTEN is mutated in 4.55% of ovarian carcinoma patients with PTEN Mutation present in 4.55% of all ovarian carcinoma patients
PTEN is mutated in 42.67% of endometrial carcinoma patients with PTEN Mutation present in 40.44% of all endometrial carcinoma patients
Germline mutations in PTEN were demonstrated to cause Cowden syndrome. This is present in 1 case per 200,000 population; however, it is likely more prevalent because many features ofCowdendisease (multiple hamartomasyndrome) are often overlooked.
Cowden syndrome is an autosomal dominant syndrome characterized by multiple hamartomas originating from all three germ-cell layers. Mucocutaneous lesions including trichilemmomas are seen in 90-100% of patients
CK 20
IS an epithelial marker that has restricted expression compared to CK 7
CK7- / CK20+ in carcinoma of colon
CK20 is less sensitive for poorly differentiated colonic carcinoma (Chin J Physiol 2006;49:298)
Primary mucinous tumors of lower GI tract (79%, Am J Surg Pathol 2006;30:1130) and primary bladder adenocarcinomas (29%
PR
Progesterone Receptor
Nuclear stain. Cytoplasmic staining only should be disregarded.
+ve in mulitiple GYN conditions:
-Cervix: Endometriod
- Uterine: Endometrial Carcinoma, Endometrial stomal tumours, leiomyoma, STUMP (Smooth Muscle Tumours of Uncertain Malignant Potential)
- Ovarian tumors: endometrioid, ependymoma, fibroma, granulosa cell (juvenile), mucinous borderline-endocervical type; serous (50%)
Endometriosis
Breast: fibroadenoma (stromal cells), myofibroblastoma, phyllodes tumors (epithelial cells), pseudoangiomatous stromal hyperplasia
Breast carcinoma (usually well differentiated tumors, lobular, mucinous/colloid, sebaceous); endometrial adenocarcinoma (75-96%)
Cervical carcinoma: endometrioid, minimal deviation
Kidney: mixed epithelial and stromal tumor
Liver: biliary cystadenoma (stroma), hepatic adenoma
Lymphangiomyomatosis
Soft tissue aggressive angiomyxoma, angiomyofibroblastoma, cellular angiofibroma
Solitary fibrous tumor
Vimentin
Is a structural protein expressed in mesenchymal cells.
\+ve in: EAC , -ve in endocervical Adeno Carcinosarcoma ESS LMS
PAX8
AKA Paired Box 8
Transcription factor critical for development of eye, thyroid, urinary and reproductive organs. Associated with tumors of thyoids, kidney / upper urinary tract and Mullerian system
\+ve staining Epithelium of Endocervix, endometrium, fallopian tubes, kidney, renal collectig ductal cells, atrophic renal tubular epithelial cells. Endometrial polyp, endometriosis, endosalpingiosis, paratubal cyst, prostatic meosnephric remnant hyperplasia Bladder clear cell adeocarcinoma Endometrial adenocarcinoma OVarian carcinoms, except mucinous types Renal cell carcinoma (90%) \+ others
AE1 / AE3
Keratin “Cocktail” that ID’d CK1-8, 10 , 14-16 and 19 but not CK17 and 18.
AKA Keratin or pankeratin
Used to confirm or rule out epithelial nautre of tissues, tumors or components of tissue
To ID metastatic carcinoma in nodes, maarrow or at frozen section
Assess depth of invasion
Stains +ve in most carcinomas
AFP
+ve staining in disease
- embryonal carcinoma, sertoli-leydic tumlurs, yolk sac tumours
- hepatoblastcoma, HCC, acinar cell carcinoma, pancreatoblastoma
ARID1A
At Rich Interactive Domain 1A (SWI-like) tumour suppressor gene
INvolved in tissure development and cellular differentiation
Loss of expression in >50% of Ovarian clear cell.
In cervix Ca
- loss of expression a poor prognostic factors
- loss in 31% of adenocarcinoma / adenosquamous carcinoma
- Endocervical-type mucinous borderline tumors may be related to endometriod tumours based on mutation and loss of expression of ARID1A
B-Catenin
+ve in Endometrioid EAC - particularly squamous morules.
also CRC and Thyroid
SMA
IHC +ve in
Myogenin
Ihc
ALK IMT
ALK is positive in 60% of IMT = Inflammatory Myofibroblastic tumour of the uterus.
SALL4
Used to differentiate primitive germ cell tumours. +ve in Dysgerminoma, YST and EC SALL4 OCT3/4 SOX2 DysG + + - YST + - + EC + + +
OCT 3/4
Used to differentiate primitive germ cell tumours. +ve in Dysgerminoma and Embryonal carcinoma
SALL4 OCT3/4 SOX2 DysG + + - YST + - + EC + + +
SOX2
Used to differentiate primitive germ cell tumours. +ve in Embyonal carcinoma
SALL4 OCT3/4 SOX2 DysG + + - YST + - + EC + + +
A primitive germ cell tumour has +ve IHC for SALL4 and OCT 3/4. Dx ?
Dysgerminoma
A primitive germ cell tumour has +ve IHC for SALL4 and SOX 2. Dx ?
Yolk sac tumour
A primitive germ cell tumour has +ve IHC for SALL4, OCT 3/4 & SOX 2. Dx ?
Embryonal Carcinoma
What is L1CAM and significance?
- L1 cell adhesion molecule (L1CAM)
- ? Biomarker in endometrial Ca to ID a subset of highly aggressive tumours with adverse clinical outcome
- Elevated level of L1CAM astd with higher risk of relapse and less well differentiated.
CD10
Cell surface marker - Differentiates
ESS CD10 + from smooth muscle tumours CD10-
Renal clear cell mets CD10+ from Gyn clear cell CD10 -
TTF1
+ve in Lung adenocarcinoma and Thyroid
Also +ve in mesonephric cervix - rarely
