Table 1.
Histological predictors of microsatellite instability.
| A | |||||
| Variable | Sensitivity % (95% CI) | Specificity % (95% CI) | Odds Ratio, Univariate (95% CI) | Odds Ratio, Multivariate (95% CI) | |
| Host response features | |||||
| Tumor-infiltrating lymphocytes (TILs) | 70 [26] | 76 [26] | 7.4 (5.4–10.3) [26] | 3.8 (2.5–5.6) [26] | |
| 72 (64–78) [27] | 82 (80–85) [27] | 9.1 (5.9–14.1) [27] | |||
| 21 [30] | 97 [30] | 9.8 (3.5–28.5) [30] | |||
| 60 (50–70) [36] | 78 (76–79) [36] | 5.2 (3.2–8.5) [36] | 3.7 (2.0–6.8) [36] | ||
| Crohn’s-like lymphocytic reaction (CLR) | 68 [26] | 54 [26] | 2.5 (1.8–3.4) [26] | 2.3 (1.6–3.5) [26] | |
| 56 (48–63) [27] | 77 (74–80) [27] | 1.9 (1.2–2.9) [27] | |||
| 49 [30] | 64 [30] | 1.7 (0.9–3.2) [30] | |||
| 69 (59–78) [36] | 45 (44–46) [36] | 1.8 (1.1–3.0) [36] | 1.1 (0.6–2.0) [36] | ||
| Peritumoral lymphocytic reaction | 86 (77–92) [36] | 42 (40–42) [36] | 4.3 (2.3–8.3) [36] | 3.7 (1.6–8.6) [36] | |
| Stromal plasma cells | 78 (68–86) [36] | 48 (46–48) [36] | 3.2 (1.9–5.6) [36] | 2.1 (1.1–4.1) [36] | |
| Tumor characteristics | |||||
| Mucinous morphology * | 53 [26] | 80 [26] | 4.6 (3.4–6.3) [26] | 1.7 (1.1–2.7) [26] | |
| 28 (21–35) [27] ** | 91 (89–93) [27] ** | 2.8 (1.7–4.8) [27] ** | |||
| 22 [30] | 93 [30] | 3.7 (1.7–8.0) [30] | |||
| 51 (41–61) [36] | 78 (77–79) [36] | 3.7 (2.3–6.0) [36] | 4.71 (2.1–10.7) [36] | ||
| 2.13 (1.3–3.4) [37] | |||||
| Medullary morphology (10–70%) | 25 [30] | 97 [30] | 12.5 (4.6–35.9) [30] | ||
| Grade † | 64 [26] † | 81 [26] † | 7.4 (5.4–10.1) [26] † | 3.4 (2.2–5.2) [26] † | |
| 38 (31–46) [27] | 82 (79–84) [27] | 1.9 (1.2–3.1) [27] | |||
| 38 [30] | 87 [30] | 4.0 (2.2–7.3) [30] | |||
| 17 (10–26) [36] | 90 (89–91) [36] | 1.8 (0.9–3.5) [36] | |||
| 32 (23–43) [36] † | 77 (76–78) [36] † | 1.6 (0.9–2.6) [36] † | |||
| Signet ring cells | 4.3 (2.2–8.7) [26] | ||||
| 13 [30] | 95 [30] | 2.7 (1.1–6.8) [30] | |||
| Lack of dirty or garland necrosis | 59 [26] | 79 [26] | 5.4 (3.9–7.4) [26] | 1.8 (1.1–2.8) [26] | |
| 26 (18–35) [36] | 89 (88–90) [36] | 2.7 (1.5–4.7) [36] | 1.4 (0.7–3.0) [36] | ||
| Cribriform pattern | 13 [30] | 72 [30] | 0.4 (0.2–0.8) [30] | ||
| Histologic heterogeneity | 4.4 (3.0–6.4) [26] | ||||
| 55 (45–65) [36] | 69 (68–70) [36] | 2.7 (1.7–4.4) [36] | |||
| Clinical/Molecular Features | |||||
| Age <50 years | 2.2 (1.3–3.8) [26] | 3.1 (1.5–6.5) [26] | |||
| 52 (44–60) [27] | 59 (56–62) [27] | 1.9 (1.3–2.9) [27] | |||
| 21 (13–29) [36] | 89 (88–90) [36] | 2.0 (1.1–3.7) [36] | 3.8 (1.8–8.0) [36] | ||
| Female | 1.4 (1.0–1.9) [26] | 1.3 (0.7–2.2) [36] | |||
| 51 (41–62) [36] | 63 (62–64) [36] | 1.8 (1.1–2.8) [36] | 1.56 (1.0–2.4) [37] | ||
| Size > or equal to 60 mm | 2.75 (1.8–4.2) [37] | ||||
| Anatomic site (right sided/proximal) | 70 [26] | 63 [26] | 4.1 (2.9–5.7) [26] | 2.2 (1.5–3.3) [26] | |
| 74 (67–81) [27] | 70 (67–73) [27] | 4.7 (3.1–7.3) [27] | |||
| 79 (70–87) [36] | 63 (61–63) [36] | 6.4 (3.6–11.2) [36] | 5.08 (2.7–9.6) [36] | ||
| 3.76 (2.4–5.9) [37] | |||||
| BRAF mutant | 13.33 (8.0–22.2) [37] | ||||
| B | |||||
| Model | Model Variables | Sensitivity (%) | Specificity (%) | Positive/Negative Predictive Value (%) | AUC or Accuracy (95% CI) |
| Greenson et al. ** [26] | TIL/HPF, well or poorly differentiated, age < 50, CLR, R-sided, lack of dirty necrosis, any mucinous differentiation | 92 ** | 46 ** | AUC 0.850 ** | |
| MsPath [27] | Age < 50, proximal location, mucinous/signet ring/undifferentiated, poorly differentiated, CLR, TILs | 93 | 55 | AUC 0.890 (0.83– 0.94) | |
| PREDICT [36] | R-sided, mucinous component, age < 50 years, TILs, peritumoral reaction, increased stromal plasma cells | 96.9 | 76.6 | 35.2/99.5 | AUC 0.924 |
| Fujiyoshi et al. [37] | Female, mucinous component, tumor size > or equal to 60 mm, proximal location, BRAF mutation | 76 | 77 | AUC 0.856 (0.806 –0.905) | |
| RERTest6 ** [38] | Proximal location, expansive growth pattern, CLR, solid pattern %, mucinous pattern %, cribriform pattern | 78.01 * | 93.39 ** | 51.8/97.9 ** | Accuracy 0.921 ** |
Table 1 summarizes individual features and composite models used for the prediction of microsatellite instability (MSI) from histology. (A) Individual variables associated with MSI are listed. * Jenkins et al. [27] included signet cell and medullary morphology with mucinous morphology. † These studies included either poorly or well differentiated tumors as associated with MSI. (B) Multivariable models and their performance in differentiating between tumors with and without MSI are presented. ** Values are presented for validation cohorts when available. Greenson et al. and RERTest6 did not include a separate validation cohort. CI: confidence interval. TIL: tumor infiltrating lymphocytes. CLR: Crohn’s-like lymphoid reaction. HPF: high power field. R-sided: right sided. AUC: area under the curve.