Table 3.
Summary of the studies used for the meta-analysis
| Author | Year | Type of study | Patient details | Median follow-up |
Tumour details | Molecular method | Tissue details | ||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| Total number of patients | Male/female | Age (years) | Ethnicity | MSI/MSS in 5-FU treated patients | |||||||
| Ribic (3) | 2003 |
Retrospective MSI study of samples from patients enrolled in multicentre US/Canada phase 3 randomized controlled trials of adjuvant chemotherapy: - 5-FU plus Leucovorin or no treatment (3 studies) - 5-FU plus levamisole or no treatment (2 studies) |
570 |
-326 male (57%) -244 female (43%) |
59.8 ± 11.2 | No details given |
MSI: 53 MSS: 230 |
7.4 years |
Colon Stage II-III Grading: well to undifferentiated Histotype: not specified |
PCR Variable number of microsatellite loci (2–11) |
At least 60% tumour cells |
| Hong (21) | 2012 |
Retrospective single centre case control study from Republic of Korea comparing: -Surgery alone -Surgery plus 5-FU -Surgery plus 5-FU and radiotherapy |
1125 |
-691 male (61.4%) -434 female (38.6%) |
61 (26–92) | No details given |
MSI: 81 MSS: 791 |
3.5 years |
Colon-rectum TNM stage I to IV Grading: well to undifferentiated Histotype: not specified |
PCR 5 microsatellite loci (Bethesda panel) |
Not given |
| Jover (24) | 2009 |
Nested prospective follow-up multicenter study, 10 hospitals in Spain Comparison of 5-FU adjuvant vs. surgery alone |
754 |
-456 male -298 female |
MMR proficient: 70.0 (11.5) MMR deficient: 68.4 (13.8) |
No details given |
MSI: 26 MSS: 225 |
4.1 years |
Tumour site not specified TNM Stage I-IV Grading: not specified Histotype: not specified |
PCR 5 microsatellite loci (Bethesda panel) ABI 310 Genetic Analyzer or immunohistochemistry (MLH1 or MSH2) |
Not given |
| Kim (18) | 2007 |
Retrospective MSI testing of patients drawn from four US clinical trials (1983–1990): - Surgery alone arm from 2 trials - 5-FU and Leucovorin from 2 trials |
1044 | No details given | No details given | No details given |
MSI: 61 MSS: 308 |
Not given |
Colon Dukes B and C Grading: not specified Histotype: not specified |
PCR 5 microsatellite loci (Bethesda panel) ABI 310 Genetic Analyzer |
At least 50% of tumour cells |
| Carethers (19) | 2004 | Case control retrospective study of patients from two hospitals in San Diego California treated with or without 5-FU adjuvant therapy | 204 |
-131 male -73 female |
65.73 _ 13.5 |
Asian 6% Black 7% Hispanic 10% White 76% Unknown 1% |
MSI: 10 MSS: 56 |
3.6 years |
Colon Stage II and III Grading: well to poor Histotype: -Mucinous 60 - Non mucinous 117 |
PCR 5 microsatellite loci (Bethesda panel) Polyacrylamide gel |
Not given |
| Ohrling (22) | 2010 | Retrospective MSI testing on patients enrolled in a randomized clinical trial 1991–1996 on surgery with or without 5-FU (plus-minus levamisole). Multicentre from 59 hospitals in Sweden | 1006 |
-559 male -447 female |
66 (24–75) | No details given |
MSI: 72 MSS: 274 |
Not given |
Colon-rectum Stage II and III Grading: well to poorly differentiated or unknown Histotype: not specified |
MLH1 and MSH2 immunohistochemistry | Not applicable |
| Klingbiel (8) | 2015 | MSI testing on patients enrolled in a randomized phase III clinical trial 2000–2002 multicentre (31 countries) on 5-FU or FOLFIRI | 1254 | No details given |
MSI: 54 (25–75) -MSS: 61 (21–76) |
No details given |
MSI: 45 MSS: 160 |
5.75 years |
Colon TNM stage I to IV Grading: well to poorly differentiated Histotype: mucinous 81% Non mucinous 18% Unknown 1% |
PCR 5 microsatellite loci (Bethesda panel) plus (BAT-25, BAT-26, D2S123, D5S346, TGFBR2, BAT-40, D17S787, D18S69, D17S250, and D18S58) |
Not given |
| Bertagnolli (20) | 2009 |
Randomised control trial phase III randomized trial comparing FU/ Leucovorin (LV) with irinotecan, FU, and LV (IFL) for postoperative adjuvant treatment. Two centres Canada and US |
1264 |
-Male 702 -Female 562 |
61 (21–85) | No details given |
MSI: 46 MSS: 302 |
6.65 years |
Colon TNM stage III Grading: well to poorly differentiated or unknown Histotype: mucinous 9.9% Non mucinous 85.1% Unknown 5% |
MLH1 and MSH2 immunohistochemistry and PCR 5 microsatellite loci (Bethesda panel) No details on analysis |
At least 60% of tumour cells using microdissection when necessary |
| Jensen (23) | 2009 | Retrospective MSI on a cohort of 5FU adjuvant treated patient in a single hospital, 1996–2003, Copenhagen | 311 |
-Male 159 -Female 152 |
-MSI: < 70 = 28; > 69 = 15 -MSS: < 70 = 217 > 69 = 51 |
No details given |
MSI: 43 MSS: 268 |
6.1 years |
Colo-rectal TNM stage II-IV Grading: well to poorly differentiated Histotype: not specified |
MLH1, MSH2, MSH6 and PMS2 immunohistochemistry and PCR 5 microsatellite loci (Bethesda panel) No details on analysis |
At least 50% of tumour cells |