Table 1. Results of Random Effects Analysis of Risk Ratio for Each Histopathologic Risk Factor for Local Recurrence, Nodal Metastasis, and Disease-Specific Death.
| Risk factor | Risk ratio (95% CI) | P value | Studies, No. | I2 statisic, % |
|---|---|---|---|---|
| Local recurrence | ||||
| Invasion beyond subcutaneous fat | 9.1 (2.8-29.2) | <.001 | 5 | 0 |
| Desmoplasia | 8.1 (4.1-15.9) | <.001 | 3 | 17 |
| Tumor thickness ≥6 mm | 4.6 (2.1-9.9) | <.001 | 3 | 1 |
| Perineural invasion | 4.1 (2.7-6.3) | <.001 | 12 | 0 |
| Lymphovascular invasion | 2.8 (1.5-5.1) | <.001 | 6 | 0 |
| Poor differentiation | 2.4 (1.2-4.8) | .02 | 12 | 0 |
| Tumor thickness ≥8 mm | 2.2 (0.6-7.8) | .23 | 1 | 0 |
| Tumor thickness ≥4 mm | 2.2 (1.0-4.6) | .05 | 2 | 0 |
| Tumor size ≥2 cm | 2.0 (1.2-3.4) | .01 | 10 | 0 |
| Tumor size ≥5 cm | 1.6 (0.4-7.5) | .52 | 1 | 0 |
| Tumor thickness ≥2 mm | 1.1 (0.5-2.2) | .85 | 2 | 0 |
| Nodal metastasis | ||||
| Tumor thickness ≥5 mm | 18.7 (2.5-139) | .004 | 1 | 0 |
| Tumor thickness ≥4 mm | 7.2 (2.1-24.3) | .002 | 1 | 0 |
| Perineural/vascular involvement | 6.9 (4.8-9.9) | <.001 | 3 | 12 |
| Cytokeratin 19 expression | 5.0 (0.7-35.8) | .11 | 1 | 0 |
| High PD-L1 expression | 3.6 (1.9-7.0) | .001 | 2 | 0 |
| LLT-1 expression | 3.4 (1.4-8.3) | .007 | 1 | 0 |
| Tumor budding | 2.9 (2.1-4.2) | <.001 | 3 | 50 |
| Desmoplasia | 2.8 (2.0-4.0) | <.001 | 2 | 0 |
| Perineural invasion | 2.7 (2.2-3.2) | <.001 | 19 | 0 |
| Poor differentiation | 2.6 (2.2-2.9) | <.001 | 18 | 29 |
| Membrane E-cadherin | 2.2 (1.7-3.0) | <.001 | 1 | 0 |
| EGFR+ | 2.2 (1.4-3.7) | .002 | 2 | 0 |
| Lymphovascular invasion | 2.1 (1.7-2.6) | <.001 | 11 | 0 |
| Cortactin | 2.0 (1.1-3.9) | .03 | 1 | 0 |
| Tumor size ≥2 cm | 2.0 (1.7-2.4) | <.001 | 13 | 0 |
| Invasion beyond subcutaneous fat | 2.0 (1.4-2.7) | <.001 | 8 | 0 |
| Tumor thickness ≥6 mm | 1.9 (1.4-2.6) | <.001 | 5 | 28 |
| Tumor thickness ≥8 mm | 1.8 (1.0-3.1) | .05 | 2 | 0 |
| Cytoplasm E-Cadherin | 1.3 (0.7-2.3) | .39 | 1 | 0 |
| ERBB3+ | 1.3 (0.7-2.4) | .44 | 1 | 0 |
| Tumor size ≥4 cm | 1.2 (0.5-2.9) | .71 | 2 | 0 |
| Tumor thickness ≥2 mm | 1.2 (0.3-4.7) | .82 | 2 | 0 |
| Tumor thickness ≥3 mm | 1.2 (0.1-9.9) | .88 | 1 | 0 |
| FAK expression | 1.0 (0.6-1.9) | .95 | 1 | 0 |
| Tumor size ≥5 cm | 1.0 (0.6-1.9) | .95 | 1 | 0 |
| ERBB4+ | 0.8 (0.4-1.6) | .58 | 1 | 0 |
| Podoplanin | 0.8 (0.5-1.3) | .38 | 1 | 0 |
| Disease-specific death | ||||
| Invasion beyond subcutaneous fat | 10.4 (3.0-36.3) | <.001 | 5 | 0 |
| Tumor size ≥5 cm | 8.9 (4.7-17.0) | <.001 | 1 | 0 |
| Lymphovascular invasion | 8.8 (3.9-19.7) | <.001 | 3 | 0 |
| Desmoplasia | 7.6 (4.9-11.8) | <.001 | 2 | 1 |
| Perineural invasion | 7.5 (4.5-12.3) | <.001 | 7 | 2 |
| Tumor thickness ≥6 mm | 6.5 (3.4-12.3) | <.001 | 1 | 0 |
| LLT-1 expression | 6.2 (1.8-21.3) | .004 | 1 | 0 |
| Poor differentiation | 5.9 (1.6-21.0) | .007 | 8 | 6 |
| Tumor size ≥2 cm | 2.9 (0.8-11.1) | .12 | 6 | 0 |
| Podoplanin | 2.8 (1.0-8.0) | .05 | 1 | 0 |
| FAK expression | 1.6 (0.8-3.2) | .23 | 1 | 0 |
| Cortactin | 1.0 (0.5-1.9) | .98 | 1 | 0 |
Abbreviations: EGFR, epidermal growth factor receptor; FAK, focal adhesion kinase; LLT-1, lectin-like transcript 1 expression; PD-L1, programmed death ligand-1.