Table 1.
Methods used for assessment of tumor budding.
| Reference | Method | Classification | Staining | Region | Area |
|---|---|---|---|---|---|
| Morodomi et al., 1989 (45) | Qualitative; subjective assessment of TB intensity | Present or absent | H&E | Invasive front | Entire invasive front |
| Hase et al., 1993 (46) | Qualitative; subjective assessment of TB intensity | None/mild (BD-1) | H&E | Invasive front | Entire invasive front |
| Moderate/severe (BD-2) | |||||
| Ono et al., 1996 (49) | Quantitative; all cancer cells with a single or solitary trabecular form with indistinct polarity (“focal dedifferentiation units”) counted along the invasive front (200×) | None (0 unit) Mild (1–20 units) Moderate (21–50 units) Severe (>50 units) | H&E | Invasive front | Entire invasive front |
| Nakamura et al., 2005 (47) | Semi-quantitative assessment of the proportion of the invasive front with TB | None, mild (<1/3 with TB) Marked (>2/3 with TB) | H&E | Invasive front | Entire invasive front |
| Moderate (1/3–2/3 with TB) | |||||
| Park et al., 2005 (50) | Quantitative assessment of TB; the number of buds is counted in three fields assessed under high-power (200×) in area of most intense TB along invasive front. TB intensity is defined as maximum number of buds within the three fields | Continuous score | H&E | Invasive front | Entire invasive front assessed under low power, 1 field (200×) counted |
| Nakamura et al., 2008 (23) | Semi-quantitative assessment of the proportion of the invasive front with TB | None/mild (low-grade) Moderate/marked (high-grade) | H&E | Invasive front | Entire invasive front |
| Ueno et al., 2002 (48) | Quantitative; invasive front scanned at low power to identify region with densest TB; buds are counted in one HPF | Low-grade (<10 buds) High-grade (≥10 buds) | H&E | Invasive front | 0.385 mm2 |
| Ueno et al., 2004 (22) | Quantitative; invasive front scanned at low power to identify region with densest TB; buds are counted in one HPF | Low-grade (<5 buds) High-grade (≥5 buds) | H&E | Invasive front | 0.785 mm2 |
| Wang et al., 2009 (24) | Conventional method: quantitative; invasive front scanned at low power to identify region with densest TB; buds are then counted in 5 high-power fields | Low-grade (<50% of HPFs exceed the median bud count of all fields) High-grade (≥50% of HPFs exceed the median bud count of all fields) | H&E | Invasive front | 0.94985 mm2 |
| Wang et al., 2009 (24) | Rapid method: quantitative; 5 HPFs are evaluated for presence of TB | Low-grade (<50% of HPFs examined positive for TB) | H&E | Invasive front | 0.94985 mm2 |
| High-grade (≥50% of HPFs examined positive for TB) | |||||
| Lugli et al., 2009 (1HPF method) (51) | Quantitative; 1 HPF counted in areas of densest TB | Low-grade (<10 buds in 1 HPF of highest density) | PanCK | Invasive front | 0.49 mm2 |
| High-grade (≥10 buds in 1 HPF of highest density) | |||||
| Ohike et al., 2010 (52) | Semi-quantitative; budding foci are identified. Buds are counted in one HPF of each focus as specified by Ueno (48). A HPF is counted as positive for TB when 5 or more tumor buds are present | Low budding (0–2 positive fields) High budding (three or more budding fields) | H&E | Invasive front | 0.785 mm2/HPF |
| Karamitopoulou et al., 2013 (10HPF method) (25) | Quantitative; 10 HPF counted in areas of densest TB | Low-grade (<100 buds total in 10 HPFs of highest density) High-grade (≥100 buds total in 10 HPFs of highest density) | PanCK | Invasive front | 0.49 mm2/HPF for a total area of 4.9 mm2 |
| Landau et al., 2014 (19) | Semi-quantitative; 5 HPFs are evaluated for presence of TB; A HPF is counted as positive for TB when 5 or more tumor buds are present | No budding (no budding fields) Focal budding (one to two budding fields) | H&E | Invasive front | 0.785 mm2/HPF |
| Extensive budding (three or more budding fields) |
TB, tumor budding; HPF, high-power field; H&E, hematoxylin and eosin; PanCK, pancytokeratin.