Stains Flashcards
Expression of CK 5/6
Expression of CK 5/6
- Mesothelioma
- Squamous/Basal Cell Carcinoma
- Salivary Gland Tumor
- Breast
- Skin Adnexa
- Urothelial Carcinoma
- Thymoma
- Endocervical Adenocarcinoma
- Synovial Sarcoma (+/-)
TFE3
TFE3
- Alveolar Soft Part Sarcoma (98%)
- Renal Cell Carcinoma With Xp11.2 Translocation (97%)
- Renal Cell Carcinoma t(X;1)(p11;q21) (76%)
- Epithelioid Hemangioendothelioma (75%)
- Granular Cell Tumor (68%)
EPITHELIAL TUMORS THAT COEXPRESS CYTOKERATIN AND VIMENTIN
EPITHELIAL TUMORS THAT COEXPRESS CYTOKERATIN AND VIMENTIN
- Thyroid Carcinoma
- Endometrial Carcinoma
- Renal Cell Carcinoma
- Mesothelioma
- Myoepithelial Carcinoma
- Metaplastic Breast Carcinoma
- Sarcomatoid Carcinoma
MESENCHYMAL TUMORS THAT COEXPRESS CYTOKERATIN AND VIMENTIN
MESENCHYMAL TUMORS THAT COEXPRESS CYTOKERATIN AND VIMENTIN
- Synovial Sarcoma
- Epithelioid Sarcoma
- Epithelioid Angiosarcoma
- Desmoplastic Small Round Cell Tumor
- Leiomyosarcoma
- Malignant Rhabdoid Tumor
- Chordoma
- Adamantinoma
BREAST DIRECTED IMMUNOMARKERS
BREAST DIRECTED IMMUNOMARKERS
- GROSS CYSTIC DISEASE FLUID PROTEIN 15 (GCDFP15)
- MAMMAGLOBIN
- NYBR 1
- GATA 3
- TFF 1
GATA3
GATA3 (nuclear)
- Breast carcinoma
- Urothelial carcinoma
- Cutaneous Basal cell carcinoma
- Cutaneous squamous carcinoma
- Trophoblastic tumors
- Endodermal sinus tumor
- Chromophobe renal cell carcinoma
- Pancreatic ductal adenocarcinoma
- Salivary gland ductal carcinoma
- Paraganglioma
ER Positive Tumors
ER Positive Tumors
- Breast
- Ovarian
- Endometrial
- Lung
PANEL OF IMMUNOMARKERS FOR THE DISTINCTION OF CK7+/ER+TUMORS
PANEL OF IMMUNOMARKERS FOR THE DISTINCTION OF CK7+/ER+TUMORS
GASTRO-INTESTINAL TRACT DIRECTED IMMUNOMARKERS
GASTRO-INTESTINAL TRACT DIRECTED IMMUNOMARKERS
- CDX2
- SATB2 (colon)
- CDH17
- CK17
- Villin
- EMERGING MARKER: LEF1
SATB2
SATB2
- Nuclear matrix – associated transcription factor and epigenetic regulator
- Positive in small bowel and colon adenocarcinoma
- Positive in lower GI neuroendocrine
- Expressed in majority of colorectal tumors including most poorly differentiated tumors
- Negative in upper GI and pancreatic tumors
- Ovarian, breast and lung adenocarinoma low
- Sensitive marker of osteoblastic differentiation
- Special AT-rich sequence binding protein 2
CADHERIN-17 (CDH 17) LIVER-INTESTINE CADHERIN
CADHERIN-17 (CDH 17) LIVER-INTESTINE CADHERIN
- Calcium-dependent transmembrane glycoprotein
- Mediates cell – cell adhesion and acts as intestinal peptide transporter
- Expressed in normal glandular epithelium of GI tract and normal pancreatic ducts
- Normal Colon/Small Intestine (100%)
- Adenocarcinoma, Colon/Rectum (98%)
- Lymphoepithelioma-like Carcinoma, Colon/Rectum (89%)
- Adenoma, Metanephric (81%)
- Adenocarcinoma, Bladder (70%)
- Adenocarcinoma, Esophageal (67%)
LEF-1 EXPRESSION
LEF-1 EXPRESSION IN COLORECTAL TUMORS
- LEF-1 is a TCF genes, activator (Lymphoid enhancer factor – 1/T cell factor)
- LEF-1 is a DNA binding protein that interacts with β catenin and activates Wnt–responsive target genes
- a/w KRAS mutation
- Pancreatoblastoma (100%)
- Solid Pseudo Papillary Tumor, Pancreas (100%)
- CLL/SLL (89%)
- Squamous Cell Carcinoma, Oropharynx (63%)
- Adenocarcinoma, Colon/Rectum (37%)
- DLBCL, Richter Transformation (21%)
- DLBCL, NOS (16%)
IMMUNOMARKERS FOR GASTROINTESTINAL
TUMORS
IMMUNOMARKERS FOR GASTROINTESTINAL
TUMORS
PANCREATIC MARKERS
PANCREATIC MARKERS
- CK17:
- Low molecular weight Cytokeratin – myoepithelial cell and basal cells
- Pancreatic DADC + 60%
- S100P:
- Belongs to the family S100 calcium binding protein
- 95 amino acid protein purified from human placenta
- Pancreatic DADC + 90%
- Maspin :
- (Serpin B5) Tumor supressor gene
- Pancreatic DADC - +
- pVHL (Von Hippel – Lindau)
- Tumor Supervisor gene
- Pancreatic DADC - +
- IMP3:
- Oncofetal RNA – binding protein
- Pancreatic DADC - +
- MUC5 AC:
- High molecular weight Glycoprotein of mucin family
- Pancreatic DADC +
DISTINCTION OF PANCREATIC DUCTAL
ADENOCARCINOMA FROM CHRONIC PANCREATITIS
DISTINCTION OF PANCREATIC DUCTAL
ADENOCARCINOMA FROM CHRONIC PANCREATITIS
LIVER DIRECTED IMMUNOMARKERS
LIVER DIRECTED IMMUNOMARKERS
- Hep PAR1
- GLYPICAN -3
- ARGINASE 1
HEPATOCELLULAR CARCINOMA MARKERS
HEPATOCELLULAR CARCINOMA
- Glypican - 3
- HePAR 1
- Arginase -1
- Alpha feto protein
- CDIO
- pCEA
- CD 34
- Glutamine Synthetase
- Heat shock protein 70
ANTIBODIES TO IDENTIFY
HEPATOCELLULAR DIFFERENTIATION
ANTIBODIES TO IDENTIFY
HEPATOCELLULAR DIFFERENTIATION
IMMUNOMARKERS FOR CONFIRMING
HEPATOCELLULAR DIFFERENTIATION
IMMUNOMARKERS FOR CONFIRMING
HEPATOCELLULAR DIFFERENTIATION
DISTINCTION OF CHOLANGIOCARCINOMA FROM METASTATIC TUMORS
DISTINCTION OF CHOLANGIOCARCINOMA FROM METASTATIC TUMORS
Metastatic Prostate Carcinoma Markers
Metastatic Prostate Carcinoma
- PSA
- PAP
- Prostein
- NKX.3
What do these stain in addition to prostate?
- PSA
- PAP
- NKX3.1
What do these stain in addition to prostate?
- PSA:
- Salivary gland tumors
- Bladder adenocarcinoma
- Periurethral glands
- Melanoma
- Anal glands
- Urachal remanants
- PAP
- NE Tumors
- NKX3.1
- Lobular Carcinoma Breast
Urothelial Carcinoma Markers
Urothelial Carcinoma
- Uroplakin III
- Thrombomodulin
- GATA-3
- CK7+/CK20+, CK5/6, p63
- Emerging markers: S100P, Uroplakin II
KIDNEY – DIRECTED ANTIBODIES
KIDNEY – DIRECTED ANTIBODIES
- PAX2/PAX8
- RCC Ma
- CD10
- CA IX
- AMACR
- cKIT
- CATHEPSIN
ADRENAL GLAND DIRECTED IMMUNOMARKERS
ADRENAL GLAND DIRECTED IMMUNOMARKERS
- INHIBIN ALPHA
- MELAN A (A103)
- CALRETININ
- Steroidogenic factor 1 (SF-1)
MESOTHELIUM – DIRECTED ANTIBODIES
MESOTHELIUM – DIRECTED ANTIBODIES
- Calretinin
- Cytokeratin 5 or 5/6
- Podoplanin (D2-40)
- WT-1 (also serous carcinoma)
- Thrombomodulin
- Mesothelin
CALRETININ
CALRETININ - cytoplasm
- Mesothelial cells/Mesothelioma
- Sex cord-stromal neoplasms
- Adrenocortical Cells
- up to 38% of Adenocarcinoma
PODOPLANIN (D2-40)
PODOPLANIN (D2-40) - membranous
Trans-membrane mucoprotein
- Mesothelial cells/Mesothelioma
- Lymphatic endothelium
- Lymphangiomas
- Kaposi sarcomas
- Angiosarcoma (subset)
- Seminomas
- Epithelioid mesotheliomas
MESOTHELIN
MESOTHELIN
- Mesothelial
- Pancreatic Adenocarcinoma
- Ovarian Serous Ca
- Urothelial carcinoma
- Lung Adenocarcinoma
- Lung Squamous cell +/-
ANTIBODIES DIRECTED AGAINST CARCINOMA
ANTIBODIES DIRECTED AGAINST CARCINOMA
- MOC 31
- Claudin -4
- BerEP4
- CEA
- TAG – 72 (B72.3)
- BG – 8
- CD - 15
DISTINCTION OF BENIGN MESOTHELIAL CELLS FROM MESOTHELIOMA
Neuroendocrine Markers
Neuroendocrine Markers
- CD56
- Synaptophysin
- Chromogranins
- PAX5
METASTATIC MERKEL CELL CARCINOMA MERKEL CELL CARCINOMA
METASTATIC MERKEL CELL CARCINOMA MERKEL CELL CARCINOMA
- CK20
- NF
- Merkel cell polyoma virus (oncovirus)
MELANOMA MARKERS
MELANOMA MARKERS
- S-100
- HMB45
- MART-1
- Tyrosinase
- SOX10
- PNL2
DESMOPLASTIC MELANOMA
- S100
- SOX10
CLEAR CELL RENAL CELL CARCINOMA
CLEAR CELL RENAL CELL CARCINOMA
- POSITIVE MARKERS
- AE1/AE3
- EMA
- RCC m
- PAX2/PAX8
- Vimentin
- CD10
- Carbonic anhydrase IX
- NEGATIVE MARKERS
- CK7
- CD117
- Ksp-cadherin
PAPILLARY RENAL CELL CARCINOMA
PAPILLARY RENAL CELL CARCINOMA
- Positive Markers:
- Keratin
- Vimentin
- RCC Ma
- Rasimase
- CK7
- Pax2/Pax8
- CD10 (67-93%)
- Negative Markers:
- CA IX
- Cathepsin K
- TFE3/TFEB
- CD117
CHROMOPHOBE RENAL CELL CARCINOMA
CHROMOPHOBE RENAL CELL CARCINOMA
- POSITIVE MARKERS
- CK7
- CD117
- PAX2/PAX8
- Ksp CADHERIN
- NEGATIVE MARKERS
- VIMENTIN
- CD10
- RCC Ma
- CA IX
RENAL ONCOCYTOMA
RENAL ONCOCYTOMA
- POSITIVE MARKERS
- CD117
- Ksp Cadherin
- PAX8
- AE1/AE3
- NEGATIVE MARKERS
- CK7
- Vimentin
- CA IX
- CD10
- RCCm
COLLECTING DUCT CARCINOMA
COLLECTING DUCT CARCINOMA
- POSITIVE
- CK7
- CEA
- 34βE12
- Ulex Europeus
- PAX8
- NEGATIVE
- CK20
- CD10
- AMACR
- CA IX
- P63
- GATA 3
DIFFERENTIAL DIAGNOSIS OF RENAL TUMORS CLEAR CELLS
DIFFERENTIAL DIAGNOSIS OF RENAL TUMORS CLEAR CELLS
DIFFERENTIAL DIAGNOSIS OF RENAL TUMORS WITH A PAPILLARY COMPONENT
DIFFERENTIAL DIAGNOSIS OF RENAL TUMORS WITH ONCOCYTIC FEATURES
DIFFERENTIAL DIAGNOSIS OF DISTAL NEPHRON-LIKE CARCINOMAS
Vascular tumor markers
Vascular tumor markers
- CD31 - good for dermal vascular stain BUT histiocytes will stain granular positive
- Erg - better marker, nuclear marker
Spindle Cell DDx Markers
CK7/CK20 negative?
CK7/CK20 negative
- Prostate
- Kidney
- Liver
- Adrenal Gland Ca
- Germ Cell: Seminoma & Yolk Sac
- Squamous cell carcinoma
CK7/CK20 Positive?
CK7/CK20 Positive
- Ovary- Mucinous carcinoma (90%)
- Bladder- Urothelial carcinoma (65-89%)
- Pancreas- Adenocarcinoma (65%)
- Bile Duct- Cholangiocarcinoma (65%)
- Stomach- Adenocarcinoma (38-40%)
- Excludes: Carcinoid, Esophageal Squamous Ca, Head/Neck Squamous Ca, Liver Hepatocellular Ca, Lung Small Cell & Squamous Ca, Ovarian NonMucinous Ca, Kidney Renal Cell Ca
CK7+/CK20-
CK7+/CK20-
- Lung- Adenocarcinoma (72-90%)
- Ovary- Non-Mucinous Ca (100%)
- Thyroid- all types (90%)
- Breast- Ductal & Lobular Ca (80-90%)
- Uterus- Endometrial carcinoma (80-85%)
- Germ Cell- Embryonal Ca (80%)
- Pleura- Mesothelioma (65-69%)
- Bladder- Urothelial (35%)
- Kidney- Renal cell carcinoma (24%)
- Pancreas- Adenocarcinoma (26-30%)
- Bile Duct- CholangioCa (30%)
- Breast- Mucinous Carcinomas
- Excludes: Colorectal Ca, Ovary Mucinous Ca, Seminoma, Yolk Sac Tumor
CK7-/CK20+
CK7-/CK20+
- Colorectal - Adenocarcinoma (75-80%)
- Skin- Merkel Cell Carcinoma (70%)
- Stomach- Gastric Adenocarcinoma (35%)
- Colorectal- Mucinous Carcinomas
- Excludes: Breast Ca, Carcinoid, CholangioCa, Esophageal Squamous, Germ cell, Lung (all types), Liver Hepatocellular Ca, Ovarian Ca, Pancreas Ca, Kidney Renal Ca, Bladder Urothelial Ca, Uterus Endometrioid
Mucinous Tumor Subsets - Staining Pattern
- Breast
- Colorectal
- Ovary
Mucinous Tumor Subsets - Staining Pattern
- Breast
- CK 7 + CK20 -
- Colorectal
- CK7 - CK20 +
- Ovary
- CK7 + CK20 +
IMP3
IMP3
- Decidua (100%)
- Normal Trophoblasts (100%)
- Pancreas: Adenocarcinoma, Papillary (>90%), PIN (57%)
- Esophagus: Barrett’s, Adenocarcinoma (>90%)
- Endocervical AIS (93%)
- Uterine/Endometrial: Papillary serous adenocarcinoma (99%), Clear Cell Carcinoma (61%)
- Ovarian Serous Cystadenocarcinoma (68%)
- Melanoma (85-90%)
- Cholangiocarcinoma, Intrahepatic (85%)
- Adenoid Cystic Carcinoma (81%)
- Mesothelioma (74%)
- Lung Adenocarcinoma (55%)
Ovarian Serous Carcinoma
Ovarian Serous Carcinoma
Mesothelin
GRANULOSA CELL TUMOR, stains
GRANULOSA CELL TUMOR
- Inhibin
- Calretinin
- Vimentin
- WT1
- CD 99
- S100
- CD56
- SF1 (steroidogenic factor)
- FOXL2 gene abnormality on xsome 3
Breast Panel
Breast Panel
Invasion?
Myoepithelial (basal): + (HMW) CK5/6, CK14 (lg ducts only), CK17, p63, S100, actin, calponin, SMA, myosin heavy chain, CD10
Luminal: + (LMW) CK7,8,18,19
Basal lamina: type IV collagen, laminin
UDH: + ER (heterogenous), + CK5/6 (mosaic pattern)
ADH/low-grade DCIS: + ER (strong, uniform), - CK5/6 (Neg in neoplastic cells, only + in surrounging myoepithelial cells)
High-grade DCIS: + HER2 (strong membranous), +p53
DCIS: p120 catenin (membranous)
LCIS: + ER (strong, diffuse), - HER2 (+pleomorphic), - p53(+pleomorphic), - E-cadherin, + p120 catenin (cytoplasmic)
Metaplastic/Spindle cell carcinoma: + HMW (variable), CK5/6, 34betaE12, +p63, +vimentin, +SMA, triple negative, +myoep/basal, “claudin low”
Fibromatosis: +Beta-catenin (nuclear, can be seen in phyllodes stroma and metaplastic), +actin, +/-desmin, +/-S100 (minority of cells)
Endometriod Endometrial Adenocarcinoma
Endometriod Endometrial Adenocarcinoma
- Positive: CK/EMA (undifferentiated focally +), ER, PR (+/- in high grade), pax-8, vimentin, WT1 (variable), Mammoglobin (~ 50%), (squamous areas + p16, p63, and CD10)
- Negative: p53, p16 (-/patchy, +/- diffusely positive in high grade), HNF-1-β, Napsin-A (+ in secretory variant)
Mismatch repair testing
- MLH1/PMS2/MSH2/MSH6 intact staining: Unlikely germline mutation (< 5%)
- MSH2/MSH6 loss: Indicative of germline mutation, genetic counseling recommended
- MLH/PMS2 loss: Recommend MLH1 promoter methylation testing
- If hypermethylated, likely represents sporadic inactivation rather than germline mutation
- If not hypermethylated, genetic counseling recommended as patient likely carries a germline mutation in MLH1
Serous Endometrial Adenocarcinoma
Serous Endometrial Adenocarcinoma
Positive: p53 and p16 (diffuse/strong + or completely negative), pax-8, IMP2, IMP3, HMGA2 (frequently), Ki-67 >75%, WT1 positive in up to 1/3, +/- HER2, +/-D2-40, +/-HNF-1-β
Negative: ER, PR, Vimentin +/-
Clear Cell Endometrial Adenocarcinoma
Clear Cell Endometrial Adenocarcinoma
Positive: HNF-1, High Ki-67, WT1/p16 (+ in ~ 1/3), C-erb-B2
Negative: ER, PR, p53, Cyclin-D1, E-cadherin
Endometrial Stromal Sarcoma, High Grade
Endometrial Stromal Sarcoma, High Grade
High-grade component
- CD10, ER, and PR typically negative
- Cyclin-D1 diffusely and strongly positive
- CD117 often positive but DOG1 negative
- β-catenin may be positive
Low-grade component
- CD10, ER, and PR positive
- Cyclin-D1 may show patchy positive, but CD117 negative
Cytogenetics
- t(10;17) with YWHAE-FAM22
- Molecular Genetics
- No KIT mutations
