Table 1.
Molecular alterations detected by immunohistochemistry (IHC) analysis in tumour samples
| Molecular alterations in tumors | Principles of immunohistochemical staining in tumoral cells | Examples |
|---|---|---|
| Chromosomal translocation | Overexpression of protein encoded by one of the genes involved in fusion or chimeric protein encoded by the two genes involved in fusion. Positive immunostaining in tumour cells | BCL2 expression in follicular lymphoma |
| Cyclin D1 expression in mantle cell lymphoma | ||
| ALK expression in different tumour cells (anaplastic lymphoma, NSCLC) | ||
| NUT expression in NUT midline carcinoma | ||
| ERG expression in prostate carcinoma | ||
| ROS1 expression in NSCLC | ||
| Gene mutation | Aberrant subcellular localisation of antigen or protein | Nuclear translocation of B‐catenin in (CRC, desmoid fibromatosis, cribriform morular variant of PTC) |
| Cytoplasmic expression of nucleophosmin in AML | ||
| Cytoplasmic expression of BRCA1 in BC. | ||
| Stabilisation and strong expression of the protein encoded by the gene mutated | P53 in different tumour types (high grade serous ovary carcinoma) | |
| Mutation specific antibodies, the antibody do not recognize the WT form of the protein (gene) | IDH1 R132H expression in gliomas | |
| EGFR L858R expression in NSCLC | ||
| EGFR Del 19 expression in NSCLC | ||
| BRAF V600E expression in different tumor types (Melanoma, PTC, CRC, others.) | ||
| Presence or lack of mutation of certain genes give an overexpression of certain surrogate markers | LCC without IGH mutation is associate with overexpression of ZAP‐70 | |
| Gene deletion or loss of function | Inactivating mutation, deletion or promoter hypermethylation of gene gives a loss of protein expression of the encoded genes | Loss of E‐cadherin staining in lobular breast carcinoma |
| Loss of INI‐1 staining in rhabdoid tumor, and epithelioid sarcoma | ||
| Loss of staining for any MMR proteins (MLH1, MSH2, MSH6, PMS2) in HNPCC with MSI | ||
| Loss of staining for parafibromin in parathyroid Carcinoma | ||
| Loss of staining for Rb in spindle cell /pleomorphic lipoma | ||
| Lack of staining for SDHB in hereditary paragangliomas and gastrointestinal stromal tumor | ||
| Loss of PTEN expression in endometrial cancer with PTEN mutation and Cowden Syndrome | ||
| Gene amplification | Increase in copy number of gene gives an overexpression of the encoded protein | HER2 strong staining in breast and gastric cancer associated with HER2 amplification |
| Strong staining for MDM2 or CDK4 associates with 12q14‐15 amplification in liposarcoma or well‐differentiated osteosarcoma. | ||
| Strong MET expression in NSCLC |
Adapted from Chan et al.53 .