Evidence for unified assessment criteria of HER2 immunohistochemistry in colorectal carcinoma Journal Article
| Authors: | Evans, M. G.; Krause, H. B.; Xiu, J.; Elliott, A.; Lou, E.; Ghani, H.; Yantiss, R. K.; Garcia-Buitrago, M.; Matsubara, Y.; Nakamura, Y.; Shia, J.; Yaeger, R.; Radovich, M.; Bryant, D. A.; Oberley, M. J.; Hechtman, J. F. |
| Article Title: | Evidence for unified assessment criteria of HER2 immunohistochemistry in colorectal carcinoma |
| Abstract: | Human epidermal growth factor receptor-2 (HER2) expression is an important biomarker for the management of RAS wild-type metastatic colorectal carcinoma (CRC). Immunohistochemistry (IHC) with reflex in situ hybridization (ISH) is accepted as a standard method of assessment, yet there are currently the following 2 sets of criteria used to interpret results: the HER2 Amplification for Colorectal Cancer Enhanced Stratification (HERACLES) criteria and the MyPathway criteria. The HER2 Amplification for Colorectal Cancer Enhanced Stratification criteria require ISH confirmation when IHC staining is 3+ in 10% to 49% of cells, whereas the MyPathway criteria mirror those for gastric HER2 assessment and do not recommend ISH confirmation in the previously referenced scenario. We aimed to assess the prevalence of HER2 3+ heterogeneity and its association with ERBB2 copy number amplification to evaluate the necessity of ISH testing when IHC staining is 3+ in <50% of cells. Next-generation sequencing of DNA (592-gene panel or whole exome sequencing) was performed for 13,208 CRC tumors submitted to Caris Life Sciences. HER2 (4B5) expression was tested using IHC. A subset of tumors was tested for ERBB2 amplification via chromogenic ISH and/or via next-generation sequencing (copy number amplification). χ2 tests or Fisher exact tests were applied where appropriate, with P values adjusted for multiple comparisons (P < .05). Of 13,208 CRCs with HER2 IHC, 87.4% (11,541/13,208) were negative for HER2 expression (≤3+ intensity and <10% tumor-cell staining) and 11.2% (1473/13,208) demonstrated at least low HER2 expression (1 to 2+ and ≥10%). Only 1.5% (194/13,208) of all tested tumors were either positive or heterogeneously positive for HER2 overexpression (3+ and ≥10%). Of these, 14% (28/194) had heterogenous HER2 overexpression (3+ staining of 10%-49% of cells). Among 22 HER2-positive/heterogenous cases with successful ISH testing, 100% (22/22) demonstrated amplification via ISH. Because the classification of tumors as HER2-positive/heterogenous using IHC correlated very closely with ISH positivity, our results suggest that ISH is likely unnecessary for CRCs with 3+ HER2 overexpression in 10% to 49% of neoplastic cells. © 2024 United States & Canadian Academy of Pathology |
| Keywords: | immunohistochemistry; adult; controlled study; human tissue; protein expression; aged; gene mutation; major clinical study; gene overexpression; gene amplification; epidermal growth factor receptor 2; genetic variability; colorectal carcinoma; microsatellite instability; erbb2; her2; copy number variation; colorectal adenocarcinoma; high throughput sequencing; chromogenic in situ hybridization; very elderly; human; male; female; article; tumor mutational burden; immunohistochemical diagnostic criteria |
| Journal Title: | Modern Pathology |
| Volume: | 38 |
| Issue: | 2 |
| ISSN: | 0893-3952 |
| Publisher: | Nature Research |
| Date Published: | 2025-02-01 |
| Start Page: | 100654 |
| Language: | English |
| DOI: | 10.1016/j.modpat.2024.100654 |
| PUBMED: | 39522645 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Article -- Source: Scopus |
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