Name some immunostains that can differentiate carcinomas/lymphomas/melanomas.
Melanoma: S100, MelanA, HMB45
Name some general prognostic markers.
Name some germane to breast cancer, and CLL.
Ki67 (MIB1) and p53
Her2 (adverse prognosis in breast cancer)
CD38 (adverse prognosis in CLL)
Name some predictive markers in breast and other cancers.
ER/PR (predicts tamoxifen response in breast)
Her2 (predicts trastuzumab response in breast)
c-Kit (predicts imatinib response in general)
Why is p53 overexpressed in p53-mutated tumors?
Inactivating mutations in p53 also disable protein degradation, resulting in overexpression.
What types of antigens should be nuclear in localization?
Transcription factors (TTF-1, CDK2, Myogenin, WT1, p53), steroid hormone receptors (ER, PR), and Ki67 (except in hyalinizing trabecular adenoma of thyroid)
What types of antigens should be cytoplasmic in localization?
The vast majority, including all intermediate filaments, contractile proteins, melanosome-associated proteins, secretory products, and other functional molecules.
What types of antigens should be membranous in localization?
Receptors, adhesion molecules, virtually all CD (cluster of differentiation) antigens. Be careful to distinguish from cytoplasmic, especially in Her2 & EGFR.
Name some antigens that have characteristic combined nuclear and cytoplasmic reactivity.
S-100, calretinin, and beta-catenin (with mutations in APC pathway, eg deep fibromatosis and colon cancer.)
What is granular immunoreactivity indicate? Examples?
Localization to cytoplasmic organelles. For example, racemase (mitochondrial/peroxisomal), P501S (golgi), and Napsin A (lysosomal).
What does punctate immunoreactivity indicate? Example?
Represents some antigens that aggregate in the cytoplasm, eg CK tangles that form in neuroendocrine carcinomas.
Name some examples in which loss of immunoreactivity is diagnostic.
DPC4 loss in pancreatic carcinoma
E-cadherin loss in lobular breast carcinoma
INI-1 loss in rhabdoid tumors and AT/RT
How are cytokeratins classified and stratified?
Moll's catalogue, in which they are separated based on gel electrophoresis.
CK1-8 are basic, CK9-20 are acidic.
CK1-6 and 9-17 are HMW, 7-8 and 18-20 are LMW.
Distinguish the distribution of HMWCKs, LMWCKs, and intermediate weight CKs.
HMWCKs: Expressed in squamous epithelia. Called "tonofilaments" ultrastructurally.
LMWCKs: Loosely distributed in the cytoplasm and unable to bundle. Found in visceral organs.
Intermediate: Usually 5, 6, and 17. Found in basal cells.
Why are certain pairs of CKs expressed jointly? Name some examples.
Keratins are heterodimers consisting of an acidic and basic heterodimer. Classic pairs include 1+10 and 8+18.
What do the following cytokeratin cocktails detect?
1. All acidic CKs except 9/12/17/18
2. All basic cytokeratins (1-8)
3. LMWCKs (8, 18)
4. HMWCKs (5>6)
5. HMWCKs (1, 5, 10, 14)
How are HMWCKs and LMWCKs differently expresses in carcinomas?
Squamous cell carcinomas express HMWCKs (but poorly-differentiated may co-express LMWCKs)
Adenocarcinomas and carcinoma of visceral epithelia express LMWCKs (but eg Pancreas, endometrium, breast, urothelial will co-express HWMCKs)
What carcinomas will not stain AE1/AE3?
HCC (expresses CK18)
RCC (can be CK-negative in general)
Neuroendocrine carcinomas (variable, Cam5.2 is better?)
Adrenocortical neoplasms (often CK negative)
What roles do EMA, CEA, and p63 have in the context of cytokeratin IHC?
EMA and CEA can be thought of as "LMWCK-equivalents" in glandular epithelia, with p63 as a "HMWCK-equivalent" in squamous, urothelial, and basal cells.
What three classes of non-carcinomas can be cytokeratin positive?
1. Tumors with true epithelial differentiation (eg epithelioid sarcomas, germ cell tumors, chordoma, mesothelioma)
2. High-grade cancers with aberrant epithelial reactivity (usually focal, with Cam5.2)
3. Gliomas and reactive astrocytes (may cross react with AE1/AE3).
How can Bowen's disease (SqIS) be distinguished from Paget's disease?
Paget's is Cam5.2+ (LMWCK).
Bowen's disease is CK903 (or CK5/6)+.
What are some uses for CK903 and CK5/6?
Urothelial (CK903+) vs prostate (CK903-)
Mesothelioma (CK5/6+) vs adenocarcinoma (CK5/6-)
UDH (CK903+) vs DCIS (CK903-)
Identifying basal cells in prostatic lesions (CK903+)
Identifing metaplastic breast cancer (CK903+)
What is the utility of Ber-EP4?
Reacts with majority of adenocarcinomas. Mostly used to distinguish lung adenocarcinoma (+) from mesothelioma (-). Especially useful in cytology of effusions.
Which organs are CK7+, CK20-?
Above the diaphragm organs (lung & mesothelioma, breast, thyroid, salivary gland) and the gyne tract (uterus, non-mucinous ovary).
Which organs are CK7-, CK20+?
Below the diaphragm GI tract (colorectal) and Merkel cell carcinoma
Which organs are CK7+, CK20+?
Peridiaphragmatic GI organs (pancreaticobiliary, stomach) and bladder, as well as mucinous ovarian.
Which organs are CK7-, CK20-?
Simple visceral epithelia (liver, kidney, prostate), adrenal gland.
Which tumors are CK+, EMA-?
Adrenocortical neoplasms (often CK- though)
Most neuroendocrine neoplasms
Embryonal carcinoma, yolk sac tumor
Which tumors are CK-, EMA+?
Plasma cell neoplasms, HL, ALCL
What carcinomas are usually CEA+?
HCC (canalicular pattern with pCEA)
Recall some vimentin-positive carcinomas.
RCC (clear cell)
Spindle cell carcinomas in general