Is there a large consistency difference between pathology diagnostic chips and traditional immunohistochemistry slides?

For interpretation indicators such as HER2, ER, and PR, the positive rates from TMA may differ from those of whole-slide sections, because the sampled areas do not cover the entire tumor heterogeneity region; if the tissue fragments are small, intensity interpretation may also be affected by edge effects or necrosis. In clinical application, I do not recommend issuing a diagnosis based solely on TMA results; it is more suitable as a quality control slide or for initial screening of research cohorts. If external quality assessment allows the use of tissue chips, the program documents should also specify the sampling rules and multi-point rules, and positive and negative control spots should be set on each chip; otherwise, it is likely to be challenged during review.

For TMA and traditional whole-slide concordance, sampling representativeness is the main consideration. A conventional 0.6 mm single core may miss heterogeneous tumors, especially for markers such as HER2; it is recommended to take 2-3 cores per case or use 1.0/1.5 mm large cores. Colorectal cancer is relatively homogeneous, and single-core concordance is acceptable, but multi-core sampling is still more reliable for quality control. In our comparisons, multi-core TMA and whole slides showed little difference in positivity rates, but intensity scores occasionally deviated; therefore, a conclusion should not be drawn based on a single core alone. Before implementation, it is best to perform paired validation using samples from your own department.

Batch-to-batch variation control is critical. Different batches of commercial TMA may exhibit differences in tissue fixation and block age, leading to staining intensity drift. It is recommended to use a fixed staining platform and reagent lot, and include positive/negative controls as well as previously validated sample spots on the same slide in each staining run; where conditions permit, quantitative or semi-quantitative scoring can be performed after scanning to reduce manual interpretation variability. For long-term use, an internal departmental quality control mean chart can be established; when values fall outside the range, troubleshoot the retrieval solution and antibody titer rather than directly adjusting the interpretation criteria.

For consistency validation, paired comparison is recommended: select 20–30 cases, section both whole slides and TMAs, stain with the same markers, and have two pathologists perform double-blind scoring. Calculate the concordance rate, Kappa, and differences in positive rates. Focus on the HER2 0/1+ boundary and ER-positive proportion grading. If discrepancies are large, adjust the number of sampling cores. Before use for external quality assessment, it is recommended to perform methodological verification in accordance with CNAS-CL02 and the reagent manufacturer's recommendations, and retain records. Using TMAs as a quality control tool rather than a direct diagnostic basis will lead to higher departmental acceptance.