IHC Panel Design for Cancer Diagnosis: Marker Selection by Tumor Type

IHC panel design is both an art and a science. Selecting the right combination of markers maximizes diagnostic accuracy while minimizing tissue use and turnaround time. For IHC protocol and troubleshooting guidance, see our IHC Staining Protocol and IHC Troubleshooting guides.

Practical Guide

The core principle of IHC panel design is to combine markers that distinguish between morphologically similar tumors. A well-designed panel includes: markers that confirm the suspected diagnosis (positive markers), markers that exclude important differential diagnoses (negative markers), and prognostic/predictive markers that guide treatment.

Lung cancer panel: TTF-1, Napsin A (adenocarcinoma); p40, CK5/6 (squamous); synaptophysin, chromogranin A, CD56 (neuroendocrine); PD-L1 (immunotherapy eligibility); ALK (fusion testing).

Breast cancer panel: ER, PR, HER2, Ki-67 (molecular subtyping); E-cadherin (lobular vs. ductal); GATA3 (breast origin in metastasis); GCDFP-15, mammaglobin (breast confirmation).

CRC panel: CDX2, CK20 (colorectal origin); CK7 (typically negative in CRC); MMR proteins (MLH1, MSH2, MSH6, PMS2 for MSI status); BRAF V600E (VE1 clone).

Melanoma panel: SOX10, S100, Melan-A, HMB-45 (melanocytic confirmation); BRAF V600E (VE1 clone for mutation screening); Ki-67 (proliferation).

Lymphoma panel: CD20, CD3, CD30, CD15, PAX5, Ki-67, BCL2, BCL6, MYC, CD10, MUM1/IRF4 (Hans algorithm for DLBCL subtyping).

Carcinoma of unknown primary (CUP): CK7/CK20 pattern, TTF-1, CDX2, PAX8, GATA3, SOX10, ER — used in a stepwise algorithm to identify the tissue of origin. For multiplex staining approaches on limited tissue, see our Multiplex IHC/IF for TME Profiling guide.

References

1. Hanahan D. Hallmarks of cancer: new dimensions. Cancer Discov. 2022;12(1):31-46. doi: 10.1158/2159-8290.CD-21-1059

2. Davis LE, Shalin SC, Tackett AJ. Current state of melanoma diagnosis and treatment. Cancer Biol Ther. 2019;20(11):1366-1379. doi: 10.1080/15384047.2019.1640032

3. Dekker E, Tanis PJ, Vleugels JLA, Kasi PM, Wallace MB. Colorectal cancer. Lancet. 2019;394(10207):1467-1480. doi: 10.1016/S0140-6736(19)32319-0

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