Supplementary Table 6 ǀ The prognostic importance of ploidy in colorectal cancer
Study (year
of
publication)
Hveem et al.
(2014)S51
Method of
ploidy
measurement
ICMsuspension
Tumour
localization
Consecutive
series
Tumour stage
Adjuvant
therapy
Diploid (%)*
End point
Significant
results
HR
Colon: 406
Rectum: 173
Yes
TNM I: 112
TNM II: 278
TNM III: 189
TNM I–III: 579
In 75% of
TNM III
patients
TNM I: 33
TNM II: 35
TNM III: 26
TNM I–III: 32
TTR
TNM II
: 2.2
TNM I
–III:
1.6
Domingo et al.
(2013)S52
ICMsuspension
CRC
No
TNM II: 445
TNM III: 461
TNM II–III: 906
Randomly
assigned
TNM II: yes
(M)
TNM III: No
(U)
TNM I–III:
yes (M)
TNM II–III:
yes (M)
Laubert et al..
(2013)S53
ICM-sections
Colon: 172
Rectum: 45
No
5-FU
DFS,
remote
metastasis
TNM I–III:
yes (M)
1.9
(OR)
Xynos et al.
(2013)S54
Mouradov et
al. (2013)S55
Gerling et al.
(2010)S56
ICM-sections
CRC
Yes
TNM I: 24
TNM II: 67
TNM III: 126
TNM I–III: 217
TNM IV: 541
OS
Yes (M)
ICMsuspension
ICM-imprints
CRC
Yes
Yes
DFS
Yes
In 130 of
the 291
patients
SCC: 25.4
UCC: 0
OS
Yes (M;
P = 0.005)
TNM I–III:
yes (M)
2.0
5.0
1.54
CRC (260
SCC and 31
UCC
Soreide et al.
(2010)S57
ICMsuspension
Colon: 121
Rectum: 65
Yes
Stage II: 546
Stage III: 651
TNM I: 25
TNM II: 84
TNM III: 76
TNM IV: 52
TNM I: 33
TNM II: 96
TNM III: 67
TNM I–III: 186
DI <1.1: 5
DI 1.1–1.8: 71
32
All: 61
DSS, RFS
TNM I–III:
NS (U)
NA
Bondi et al.
(2009)S58
ICMsuspension
Colon
Yes
In patients
with
stage III
disease
only
NA
Dukes A: 33
Dukes B: 39
Dukes C: 41
Dukes D: 12
Dukes A–D:
34
CSS, RFS
Dukes B:
yes (M)
Dukes A–D:
yes (M)
NA
Dukes A: 10
Dukes B: 107
Dukes C: 59
Dukes D: 43
Dukes A–D: 210
Yes
DFS
32
M0: 29
M+: 15
TNM I–III: 22
1.6
4.1
(OR)
NA
Buhmeida et
al. (2009)S59
ICM-sections
Colon: 70%
Rectum:30%
Yes
TNM II: 253
NA
NA
DFS, DSS
DFS: NS
DSS: yes
(M)
DSS:
29
(OR)
Banerjea et al.
(2008)S60
FCM-F
CRC
Yes
TNM I: 11
TNM II: 56
TNM III: 24
TNM I–III: 91
In 46% of
the
patients
NA
DFS
TNM I–III:
NS (U)
NA
Chang et al.
(2006)S61
FCM-F
Colon: 139
Rectum: 94
Yes
TNM I: 30
TNM II: 72
TNM III: 73
TNM IV: 38
TNM I–IV: 213
NA
TNM I–IV: 33
DFS, OS
NA
Santagostino
et al. (2006)S62
FCM-F; paired
tumour and
normal tissue
samples
Colon: 59
Rectum: 8
Yes?
TNM I: 13
TNM II: 22
TNM III: 20
TNMIV: 12
TNM I–IV: 67
NA
OS,
DSS, DFS
Sinicrope et al.
(2006)S63
FCM-A
Colon
No
TNM II:158
TNM III: 370
TNM II–III: 528
NA
TNM I: 46
TNM II: 55
TNM III: 25
TNM IV: 0
TNM I–IV: 34
TNM II–III: 42
Bendardaf et
al. (2004)S64
ICMsuspension
CRC
Yes
Mixed, but
mostly stage III–
IV (56% M1)
Irinotecan
and 5-FU
11
RR, OS
TNM I–IV:
P = 0.28 for
DFS (U),
and
P = 0.17 for
OS (U)
TNM I–IV:
P = 0.04 (U)
for DFS;
P = 0.035
(U) for OS
TNM II–III:
P = 0.0001
for DFS (M);
P = 0.0003
for OS (M) 
Diploid
tumour RR:
17%
Aneuploid
DFS,
OS
NA
NA
NA
tumour RR:
48%
Tetraploid
tumour RR:
20%
Multiploid
tumour RR:
86%
Dukes B2:
no (U)
Dukes C:
yes (M)
Dukes B2–
C: yes (M)
TNM I–IV:
no (U)
Garrity et al.
(2004)S65
FCM
CRC
No
Dukes B2: 92
Dukes C: 274
Dukes B2–C:
366
81%
NA
OS, DFS
Lin et al.
(2003)S66
FCM-F
Colon: 135
Rectum: 185
Yes
NA
FCM-F; paired
tumour and
normal tissue
samples
CRC
Yes
TNM I: 23
TNM II: 30
TNM III: 35
TNM IV: 13
TNM I–IV: 27
Dukes A–B:33
Dukes C–D:14
Dukes A–D:25
2-yr DFS
Bazan et al.
(2002)S67
DFS, OS
Dukes A–D:
yes (M)
2.8
Berczi et al.
(2002)S68
FCM-A
Rectum
Yes
TNM I: 24
TNM II: 31
TNM III: 60
TNM IV: 29
TNM I–IV:144
Dukes A: 40
Dukes B: 51
Dukes C: 41
Dukes D: 28
Dukes A–D: 160
TNM I: 10
TNM II: 25
TNM III: 17
TNM I–III: 52
NA
TNM I–III: 48
OS
NA
Chen et al.
(2002)S69
FCM-F
Colon: 281
Rectum: 387
Yes
NA
Dukes A–C:
41
CSS
Geido et al.
(2002)S70
FCM-F; multisample
CRC
NA
Dukes A: 49
Dukes B: 401
Dukes C: 216
Dukes A–C: 668
Dukes A: 13
Dukes B: 68
Dukes C: 42
Dukes D: 12
TNM I–III:
yes
(P = 0.048;
U)
Dukes A–C:
yes
(P = 0.03; U)
NA
Dukes A: 61
Dukes B: 22
Dukes C: 26
Dukes D: 25
OS
NA
Russo et al.
(2002)S71
FCM-F; paired
tumour and
normal tissue
samples
CRC
Yes
NA
Dukes A–D:
25
DFS, OS
Buglioni et al.
(2001)S72
FCM-F
CRC
Yes
Dukes A: 40
Dukes B: 51
Dukes C: 41
Dukes D: 28
Dukes A–D: 160
Dukes B2: 94
Dukes C:
yes
(P = 0.016;
U)
Dukes A–D:
yes (M)
5-FU in 36
patients
Dukes B2: 35
DFS,
OS
Dukes B2:
yes (M)
De Angelis et
al. (2001)S73
FCM
CRC
No
NA
Dukes A–D:
37
OS
Dukes A–D:
yes
(P = 0.02; U)
Karelia et al.
(2001)S74
FCM-A
Colon: 19
Rectum: 60
Yes
Dukes A: 1
Dukes B: 34
Dukes C: 20
Dukes D: 11
Dukes A–D: 66
TNM I: 3
TNM II: 42
TNM III: 34
TNM I–III: 79
DFS:
3.4
OS:
4.5 for
multiploidy
NA
TNM I–III: 59
OS
Risques et al.
(2001)S75
FCM-A
CRC
Yes
Dukes A–B: 69
Dukes C: 39
Dukes A–C: 108
Yes: for
Dukes
B2–C
Disease
NA
Dukes A–C:
30
DFS,
OS
EminovicBehrem et al.
(2000)S76
FCM-A
CRC
NA
Dukes A: 23
Dukes B: 59
Dukes C: 12
Dukes A–C: 94
NA
Dukes A–C:
49
OS
TNM I–III:
yes
(P = 0.0001;
M)
Dukes A–C:
yes for OS
(M), using
aneuploidy
index
Dukes A–C:
no (U)
NA
NA
NA
NA
2.6
NA
3.9
NA
Hawkins et al.
(2000)S77
FCM-F
CRC
No?
Dukes A: 8
Dukes B: 16
Dukes C: 15
Dukes D: 7
Dukes A–D: 46
NA
Dukes A: 62
Dukes B: 44
Dukes C: 36
Dukes D: 71
Dukes A–D:46
OS, RFS
Dukes A–D:
no (U)
NA
Lammering et
al. (2000)S78
FCM-A of preRT biopsy and
post-RT
resection
samples
FCM-F
Rectum
NA
TNM I: 69
TNM II–III: 47
TNM I–III: 116
NA (preoperative
RT)
Pre-RT: 26
Post-RT: 52
OS
TNM I–III:
yes
(P = 0.048;
M)
NA
CRC
Yes
Dukes A: 21
Dukes B: 117
Dukes C: 111
Dukes A–C: 249
NA
Dukes A–C:
31
OS
Dukes B:
yes
(P = 0.046;
U)
Dukes A and
C: no (U)
Dukes A–C:
yes
(P = 0.035;
U)
NA
Purdie et al.
(2000)S79
*The figures given here for percentage of tumours that were diploid are overall diploid frequencies.
Abbreviations: 5-FU, 5-fluorouracil; CRC, colorectal carcinoma; CSS, cancer-specific survival; DFS,
disease-free survival; DI, DNA index; DSS, disease-specific survival; FCM, flow cytometry; FCM-A,
flow cytometry using archival material; FCM-F, flow cytometry using fresh or frozen material; HR,
hazard ratio; ICM, image cytometry; M, on multivariate analysis; M+, distant metastasis; M0, no
metastasis; mo, month; N+, lymph-node positive; N0, lymph-node negative; NA, not
applicable/available; NS, not significant; OR, odds ratio; OS, overall survival; RFS, recurrence-free
survival; RR, response rate; RT, radiotherapy; SCC, sporadic colorectal carcinoma; TTR, time to
recurrence; U, on univariate analysis; UCC, colorectal cancer in colitis; yr, year.
S51.
Hveem, T.S. et al. Prognostic impact of genomic instability in colorectal cancer. Br.J.Cancer
110, 2159-2164 (2014).
S52.
Domingo, E. et al. Use of multivariate analysis to suggest a new molecular classification of
colorectal cancer. J.Pathol. 229, 441-448 (2013).
S53.
Laubert, T. et al. Aneuploidy and elevated CEA indicate an increased risk for metachronous
metastasis in colorectal cancer. Int. J. Colorectal Dis. 28, 767-775 (2013).
S54.
Xynos, I.D. et al. Factors Influencing Survival in Stage IV Colorectal Cancer: The Influence of
DNA Ploidy. ISRN Gastroenterol 2013, 490578 (2013).
S55. Mouradov, D. et al. Survival in stage II/III colorectal cancer is independently predicted by
chromosomal and microsatellite instability, but not by specific driver mutations. Am. J.
Gastroenterol. 10, 1785-1793 (2013).
S56.
Gerling, M. et al. High Frequency of Aneuploidy Defines Ulcerative Colitis-Associated
Carcinomas: A Comparative Prognostic Study to Sporadic Colorectal Carcinomas. Ann.Surg.
252, 74-83 (2010).
S57.
Soreide, K. et al. Microsatellite instability and DNA ploidy in colorectal cancer: potential
implications for patients undergoing systematic surveillance after resection. Cancer 115,
271-282 (2009).
S58.
Bondi, J., Pretorius, M., Bukholm, I. & Danielsen, H. Large-scale genomic instability in colon
adenocarcinomas and correlation with patient outcome. APMIS 117, 730-736 (2009).
S59.
Buhmeida, A. et al. DNA image cytometry predicts disease outcome in stage II colorectal
carcinoma. Anticancer Res. 29, 99-106 (2009).
S60.
Banerjea, A., Hands, R.E., Powar, M.P., Bustin, S.A. & Dorudi, S. Microsatellite and
chromosomal stable colorectal cancers demonstrate poor immunogenicity and early disease
recurrence. Colorectal Dis. 11, 601-608 (2009).
S61.
S62.
S63.
S64.
S65.
S66.
S67.
S68.
S69.
S70.
S71.
S72.
S73.
S74.
S75.
S76.
S77.
S78.
S79.
Chang, S.C. et al. Relationship between genetic alterations and prognosis in sporadic
colorectal cancer. Int.J.Cancer 118, 1721-1727 (2006).
Santagostino, A. et al. Prospective study on prognostic significance of DNA ploidy and Ki-67
expression in colorectal cancer. J. Biol. Regul. Homeost. Agents 21, 13-20 (2007).
Sinicrope, F.A. et al. Microsatellite instability accounts for tumor site-related differences in
clinicopathologic variables and prognosis in human colon cancers. Am. J. Gastroenterol. 101,
2818-2825 (2006).
Bendardaf, R. et al. Response to chemotherapy (irinotecan plus 5-fluorouracil) in colorectal
carcinoma can be predicted by tumour DNA content. Oncology 66, 46-52 (2004).
Garrity, M.M. et al. Prognostic value of proliferation, apoptosis, defective DNA mismatch
repair, and p53 overexpression in patients with resected Dukes' B2 or C colon cancer: a
North Central Cancer Treatment Group Study. J.Clin Oncol. 22, 1572-1582 (2004).
Lin, J.K. et al. Prognostic value of DNA ploidy patterns of colorectal adenocarcinoma.
Hepatogastroenterology 50, 1927-1932 (2003).
Bazan, V. et al. DNA ploidy and S-phase fraction, but not p53 or NM23-H1 expression,
predict outcome in colorectal cancer patients. Result of a 5-year prospective study. J. Cancer
Res. Clin. Oncol. 128, 650-658 (2002).
Berczi, C., Bocsi, J., Bartha, I., Math, J. & Balazs, G. Prognostic value of DNA ploidy status in
patients with rectal cancer. Anticancer Res. 22, 3737-3741 (2002).
Chen, M.H., Chang, A.R. & Lo, S.Y. The usefulness of cytodiagnosis and DNA cytometry on
nasopharyngeal brush smears for the diagnosis of nasopharyngeal carcinoma. Head Neck 24,
223-227 (2002).
Geido, E. et al. Combined DNA flow cytometry and sorting with k-ras2 mutation spectrum
analysis and the prognosis of human sporadic colorectal cancer. Cytometry 50, 216-2124
(2002).
Russo, A. et al. p53 mutations in L3-loop zinc-binding domain, DNA-ploidy, and S phase
fraction are independent prognostic indicators in colorectal cancer: a prospective study with
a five-year follow-up. Cancer Epidemiol. Biomarkers Prev. 11, 1322-1331 (2002).
Buglioni, S. et al. p53 nuclear accumulation and multiploidy are adverse prognostic factors in
surgically resected stage II colorectal cancers independent of fluorouracil-based adjuvant
therapy. Am.J.Clin Pathol. 116, 360-368 (2001).
De Angelis, P.M., Stokke, T., Beigi, M., Mjaland, O. & Clausen, O.P. Prognostic significance of
recurrent chromosomal aberrations detected by comparative genomic hybridization in
sporadic colorectal cancer. Int. J. Colorectal Dis. 16, 38-45 (2001).
Karelia, N.H. et al. Prognostic significance of DNA aneuploidy and p21 ras oncoprotein
expression in colorectal cancer and their role in the determination of treatment modalities.
Int. J. Biol. Markers 16, 97-104 (2001).
Risques, R.A. et al. Redefining the significance of aneuploidy in the prognostic assessment of
colorectal cancer. Lab. Invest. 81, 307-315 (2001).
Eminovic-Behrem, S. et al. Prognostic significance of DNA ploidy pattern and nucleolar
organizer regions (AgNOR) in colorectal carcinoma. Croat. Med. J. 41, 154-158 (2000).
Hawkins, N.J., Tomlinson, I., Meagher, A. & Ward, R.L. Microsatellite-stable diploid
carcinoma: a biologically distinct and aggressive subset of sporadic colorectal cancer.
Br.J.Cancer 84, 232-236 (2001).
Lammering, G., Taher, M.M., Gruenagel, H.H., Borchard, F. & Porschen, R. Alteration of DNA
ploidy status and cell proliferation induced by preoperative radiotherapy is a prognostic
factor in rectal cancer. Clin. Cancer Res. 6, 3215-3221 (2000).
Purdie, C.A. & Piris, J. Histopathological grade, mucinous differentiation and DNA ploidy in
relation to prognosis in colorectal carcinoma. Histopathology 36, 121-126 (2000).