Background
Methods
Patient selection and data collection
Immunohistochemical and PCR analysis
Outcomes and statistical analysis
Results
Characteristics | N° of Patients (%) | Median (range) |
---|---|---|
Age (years) | 94 | 66 (35-89) |
Gender | ||
Male | 53 (56%) | |
Female | 41 (44%) | |
Size, cm | 3 (0-9.5) | |
Histological Grade | ||
1 | 5 (5%) | |
2 | 69 (73%) | |
3 | 18 (19%) | |
4 | 1 (1%) | |
(Unknown)¥
| 1 (1%) | |
Tumor Size (T) | ||
1-2 | 15 (16%) | |
3-4 | 78 (83%) | |
(Unknown) ¥
| 1 (1%) | |
Nodes (N) | ||
Positive | 65 (69%) | |
Negative | 27 (29%) | |
(Unknown) ¥
| 2 (2%) | |
TNM Stage | ||
IA | 2 (2%) | |
IB | 3 (3%) | |
IIA | 21 (22%) | |
IIB | 63 (67%) | |
III | 3 (3%) | |
IV | 2(2%) | |
Resection Margins | ||
R0 | 66 (70%) | |
R1 | 27 (29%) | |
(Unknown) ¥
| 1 (1%) | |
Vital status | ||
Alive | 34 (36%) | |
Dead | 60 (64%) |
RRM1 Expression | ERCC1 Expression | |||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
RRM1 mRNA expression (PCR) | RRM1 protein expression (IHC) | ERCC1 mRNA expression (PCR) | ERCC1 protein expression (IHC) | |||||||||||||
Covariate | High | Low | N |
p
| High | Low | N |
p
| High | Low | N |
p
| High | Low | N |
p
|
Age (years) | ||||||||||||||||
Young (<65.5) | 4 (21%) | 15 (79%) | 49 | 1.0 | 14 (30%) | 32 (70%) | 93 | 0.51 | 19 (48%) | 21 (53%) | 79 | 0.36 | 29 (62%) | 18 (38%) | 94 | 0.41 |
Old (> 65.5) | 6 (20%) | 24 (80%) | 18 (38%) | 29 (62%) | 14 (36%) | 25 (64%) | 24 (51%) | 23 (49%) | ||||||||
Size (cm) | ||||||||||||||||
Small (<2.0) | 1 (9%) | 10 (91%) | 49 | 0.42 | 5 (26%) | 14 (74%) | 93 | 0.59 | 4 (31%) | 9 (69%) | 79 | 0.54 | 11 (55%) | 9 (45%) | 94 | 1.0 |
Large (> 2.0) | 9 (24%) | 29 (76%) | 27 (36%) | 47 (64%) | 29 (44%) | 37 (56%) | 42 (57%) | 32 (43%) | ||||||||
Gender | ||||||||||||||||
Female | 6 (24%) | 19 (76%) | 49 | 0.73 | 14 (35%) | 26 (65%) | 93 | 1.0 | 13 (37%) | 22 (63%) | 79 | 0.50 | 25 (61%) | 16 (39%) | 94 | 0.53 |
Male | 4 (17%) | 20 (83%) | 18 (34%) | 35 (66%) | 20 (45%) | 24 (55%) | 28 (53%) | 25 (47%) | ||||||||
Race | ||||||||||||||||
White | 4 (12%) | 29 (88%) | 48 | 0.11 | 23 (35%) | 43 (65%) | 92 | 1.0 | 22 (42%) | 31 (58%) | 78 | 1.0 | 36 (55%) | 30 (45%) | 93 | 0.82 |
Non-White | 5 (33%) | 10 (67%) | 9 (35%) | 17 (65%) | 11 (44%) | 14 (56%) | 16 (59%) | 11 (41%) | ||||||||
Histological Grade¥
| ||||||||||||||||
1 or 2 | 7 (19%) | 29 (81%) | 48 | 1.0 | 22 (30%) | 51 (70%) | 92 | 0.10 | 27 (45%) | 33 (55%) | 78 | 0.43 | 42 (57%) | 32 (43%) | 93 | 0.80 |
3 or 4 | 2 (17%) | 10 (83%) | 10 (53%) | 9 (47%) | 6 (33%) | 12 (67%) | 10 (53%) | 9 (47%) | ||||||||
Lymph Nodes¥
| ||||||||||||||||
No LN positive | 4 (31%) | 9 (69%) | 47 | 0.24 | 9 (35%) | 17 (65%) | 91 | 1.0 | 14 (64%) | 8 (36%) | 77 | 0.024 | 16 (59%) | 11 (41%) | 92 | 0.82 |
At least 1 LN positive | 5 (15%) | 29 (85%) | 23 (35%) | 42 (65%) | 19 (35%) | 36 (65%) | 36 (55%) | 29 (45%) | ||||||||
Depth of Tumor (pT) ¥
| ||||||||||||||||
T1 and T2 | 2 (20%) | 8 (80%) | 48 | 1.0 | 4 (27%) | 11 (73%) | 92 | 0.56 | 4 (36%) | 7 (64%) | 78 | 0.75 | 5 (33%) | 10 (67%) | 93 | 0.087 |
T3 and T4 | 7 (18%) | 31 (82%) | 28 (36%) | 49 (64%) | 29 (43%) | 38 (57%) | 47 (60%) | 31 (40%) |
Overall Survival | Disease-Free Survival | ||||||||
---|---|---|---|---|---|---|---|---|---|
Covariate | Median [months] (95% CI) | N | Total N | Log-rank p-value | Median [months] (95% CI) | N | Total N | Log-rank p-value | |
Overall
| 18 (14, 25) | 94 | 94 | 12 (8, 19) | 64 | 64 | |||
Age (year)
|
Young (≤ 65.5)
| 20 (16, 47) | 47 | 94 | 0.087 | 11 (8, 19) | 38 | 64 | 0.71 |
Old (> 65.5)
| 15 (9, 24) | 47 | 14 (7, 25) | 26 | |||||
Size (cm)
|
Small (≤ 2.0)
| 25 (9, 47) | 20 | 94 | 0.60 | 21 (8, ∞) | 12 | 64 | 0.17 |
Large (> 2.0)
| 17 (13, 22) | 74 | 11 (7, 17) | 52 | |||||
Gender
|
Female
| 20 (12, 34) | 41 | 94 | 0.89 | 10 (7, 17) | 32 | 64 | 0.12 |
Male
| 18 (12, 25) | 53 | 19 (9, 46) | 32 | |||||
Race
|
White
| 17 (13, 26) | 66 | 93 | 0.65 | 14 (8, 25) | 43 | 64 | 0.59 |
NonWhite
| 22 (8, 26) | 27 | 10 (6, 19) | 21 | |||||
Grade
|
1/2
| 20 (16, 26) | 74 | 93 | 0.003 | 14 (10, 19) | 52 | 64 | 0.031 |
3/4
| 7 (6, 14) | 19 | 6 (2, 25) | 12 | |||||
Lymph Nodes
|
0
| 26 (22, 48) | 27 | 92 | 0.009 | 21 (14, ∞) | 20 | 63 | 0.008 |
≥ 1
| 15 (12, 20) | 65 | 9 (7, 12) | 43 | |||||
Tumor size by
|
1/2
| 12 (6, 22) | 15 | 93 | 0.45 | 19 (5, ∞) | 9 | 64 | 0.31 |
TNM stage
|
3/4
| 18 (15, 26) | 78 | 11 (8, 19) | 55 | ||||
Treatment
|
Chemo
| 20 (15, 26) | 82 | 94 | <.001 | 14 (9, 19) | 62 | 64 | 0.013 |
No chemo
| 6 (3, ∞) | 12 | 5 | 2 | |||||
RRM1
|
Low
| 20 (15, 25) | 61 | 93 | 0.50 | 12 (8, 21) | 40 | 63 | 0.76 |
IHC Interp. |
High
| 14 (8, 48) | 32 | 17 (5, ∞) | 23 | ||||
RRM1
|
Low
| 24 (16, 26) | 39 | 49 | 0.21 | 14 (8, 21) | 28 | 34 | 0.48 |
PCR Interp. |
High
| 48 (3, 48) | 10 | 17 (11, 17) | 6 | ||||
ERCC
|
Low
| 20 (12, 25) | 41 | 94 | 0.83 | 14 (8, 25) | 26 | 64 | 0.39 |
IHC Interp. |
High
| 17 (12, 26) | 53 | 12 (7, 19) | 38 | ||||
ERCC
|
Low
| 16 (12, 25) | 46 | 79 | 0.39 | 10 (7, 19) | 29 | 56 | 0.74 |
PCR Interp. |
High
| 22 (9, 48) | 33 | 14 (6, 21) | 27 |
A. Survival in Pancreatic CA: Relative Gene Expression (N = 42) | |||
---|---|---|---|
Multivariate | |||
Variable (Comparison) | Hazard Ratio (95% CI) |
p -value†
| |
Year of Diagnosis | one year increase | 0.97 (0.69, 1.35) | 0.836 |
Age | ≥ 65.5 vs. < 65.5 | 1.53 (0.54, 4.33) | 0.419 |
Positive Lymph Nodes | Any vs. None | 0.80 (0.29, 2.22) | 0.672 |
Treatment received | No Chemo vs. Chemo | 13.09 (1.71,100.2) | 0.013 |
ERCC1 Rel Gene Expression (PCR) | Low vs. High | 0.86 (0.26, 2.81) | 0.797 |
RRM1 Rel Gene Expression (PCR) | Low vs. High | 17.58 (1.45,213.5) | 0.024 |
B. Survival in Pancreatic CA: Protein Expression by IHC Score (N = 91)
| |||
Multivariate
| |||
Variable (Comparison)
|
Hazard Ratio
(95% CI)
|
p
-value
†
| |
Year of Diagnosis | one year increase | 0.86 (0.71, 1.02) | 0.088 |
Age | ≥ 65.5 vs. < 65.5 | 1.36 (0.74, 2.52) | 0.320 |
Positive Lymph Nodes | Any vs. None | 2.34 (1.21, 4.52) | 0.011 |
Treatment | No Chemo vs. Chemo | 3.04 (1.25, 7.41) | 0.014 |
ERCC1 IHC | Low vs. High | 0.96 (0.53, 1.74) | 0.888 |
RRM1 IHC | Low vs. High | 0.83 (0.42, 1.63) | 0.583 |
Overall Survival | Disease-Free Survival | ||||||||
---|---|---|---|---|---|---|---|---|---|
Covariate | Median [months] (95% CI) | N | Total N | Log-rank
p-value | Median [months] (95% CI) | N | Total N | Log-rank
p-value | |
Overall
| 20.3 (15, 25.5) | 82 | 82 | 13.5 (9.3, 19.4) | 62 | 62 | |||
Age
|
Young (≤ 65.5)
| 22 (15.6, 47.2) | 44 | 82 | 0.18 | 10.5 (8, 19.3) | 38 | 62 | 0.48 |
Old (> 65.5)
| 17 (9.6, 25.5) | 38 | 14 (8, ∞) | 24 | |||||
Size
|
Small (≤ 2.0)
| 25 (9.6, 47.2) | 18 | 82 | 0.45 | 20.5 (8.3, ∞) | 12 | 62 | 0.21 |
Large (> 2.0)
| 17.7 (14.8, 25.5) | 64 | 12 (8, 17.3) | 50 | |||||
Gender
|
Female
| 22 (14.8, 34.5) | 36 | 82 | 0.85 | 10 (6.5, 17.3) | 31 | 62 | 0.12 |
Male
| 20 (14.4, 25.5) | 46 | 19.3 (9.4, 46) | 31 | |||||
Race
|
White
| 20 (14.8, 26.5) | 59 | 82 | 0.88 | 13.5 (8, 25.5) | 42 | 62 | 0.65 |
Non-White
| 22 (9.2, 26.2) | 23 | 10.3 (5.5, 592) | 20 | |||||
Grade
|
1/2
| 20.5 (16, 25.5) | 67 | 82 | 0.028 | 14 (10.3, 20.5) | 51 | 62 | 0.0503 |
3/4
| 14.5 (6.5, 26.5) | 15 | 9.4 (2, 25.5) | 11 | |||||
Lymph Nodes
|
0
| 25.5 (15, 48.5) | 26 | 81 | 0.038 | 20.5 (13.5, ∞) | 20 | 61 | 0.012 |
≥ 1
| 16 (13, 20.3) | 55 | 9.4 (6.5, 14) | 41 | |||||
Tumor
|
1/2
| 20 (6.5, 47) | 13 | 82 | 0.59 | 19.5 (5.5, ∞) | 8 | 62 | 0.21 |
(TNM)
|
3/4
| 20.5 (15, 26) | 69 | 12 (8, 19.3) | 54 | ||||
RRM1
|
Low
| 20.3 (15, 25.5) | 55 | 81 | 0.87 | 13.5 (8, 20.5) | 39 | 61 | 0.84 |
IHC Interp
|
High
| 47.8 (8.7, 48) | 26 | 16.6 (5.5, ∞) | 22 | ||||
RRM1
|
Low
| 24 (17, 26) | 37 | 44 | 0.070 | 14 (9.4, 25.5) | 26 | 32 | 0.62 |
PCR Interp
|
High
| 48 (*, *) | 7 | 17.3 (10.5, 17.3) | 6 | ||||
ERCC
|
Low
| 20.3 (14.8, 26.5) | 35 | 82 | 0.88 | 14 (9.4, 31.5) | 25 | 62 | 0.36 |
IHC Interp
|
High
| 17 (13.3, 26) | 47 | 12 (6.5, 20.5) | 37 | ||||
ERCC
|
Low
| 17 (14.5, 24.7) | 39 | 68 | 0.23 | 10 (7, 25.5) | 28 | 54 | 0.74 |
PCR Interp
|
High
| 24 (11, 63.7) | 29 | 13.5 (8, 20.5) | 26 |
RRM1 | ERCC1 | |||
---|---|---|---|---|
RRM1 IHC | RRM1Relative Gene Exp | ERCC1 Relative Gene Exp | ERCC IHC | |
RRM1 IHC | 1.00 | 0.26 | 0.13 | 0.18 |
P = 0.07 |
P = 0.26 |
P = 0.09 | ||
N = 93 | N = 48 | N = 75 | N = 93 | |
RRM1 Rel | 1.00 | 0.57 | 0.06 | |
Gene Exp |
P < 0.0001 |
P = 0.66 | ||
N = 49 | N = 44 | N = 49 | ||
ERCC1 Rel | 1.00 | 0.21 | ||
Gene Exp |
P = 0.07 | |||
N = 76 | N = 76 | |||
ERCC1 IHC | 1.00 | |||
N = 94 |