Orcein is a more sensitive stain than EVG for detecting large vessel (venous) invasion in colorectal cancer

BACKGROUND: Large vessel invasion (VI) is a well-established adverse prognostic factor in colorectal cancer (CRC). Assessment based solely on haematoxylin-eosin (H&E)-stained sections is relatively insensitive, prompting professional medical societies to recommend elastin stains. However, comparative data between elastin stains, such as orcein or elastic Verhoeff-Van Gieson (EVG), remain limited. DESIGN: Seventy-eight random CRC resections (≥ pT1) from 2023 to 2025 were analysed. H&E slides were evaluated for VI to facilitate ordering additional studies to complete two sets of orcein, EVG, and H&E recut on average for each case. Sets lacking the lesion on deeper sections were excluded, yielding 155 sets. All H&E slides were evaluated for VI followed by elastin stains. VI status and elastin stain quality (partial: 50%-99% vs. circumferential: 100% of the vessel wall) were assessed by at least two pathologists. RESULTS: Elastin stain confirmed VI was identified in 30% of slide sets (46% of resections). Using orcein with H&E as the reference comparator (sensitivity 100%, specificity 100%), H&E alone demonstrated 70% sensitivity and 80% specificity. EVG failed to detect 21% of cases identified by orcein (EVG sensitivity 79%, specificity 100%; p = 0.002). Orcein demonstrated a significantly higher circumferential staining rate than EVG (78% vs. 43%; p < 0.001). CONCLUSION: H&E assessment alone is less accurate than evaluation supplemented with elastin stains for detecting VI. While EVG is highly specific, it is less sensitive than orcein, in part due to diminished staining and lower background contrast. These findings support the use of orcein to optimize VI detection in CRC.