AJCP / Original Article
Nuclear Grade Plus Proliferation Grading System for
Invasive Ductal Carcinoma of the Breast
Validation in a Tertiary Referral Hospital Cohort
Maria Papadimitriou, MD,1 Sarantos Kaptanis, MD, JD,2 Evangelos Polymeropoulos, MD,3
Grigorios Mitsopoulos, MD, FRCPath,4 Dimitris Stogiannis, PhD,5 Chrys Caroni, PhD,6 George
Vaiopoulos, MD, PhD,7 Joannis G. Panayiotides, MD, PhD,8 and Petros Karakitsos, MD, PhD8
From the 1Laikon Hospital, 1st Internal Medicine Department, University of Athens Medical School, Athens, Greece; 2Barts Cancer Institute, Queen Mary,
University of London, London, England; 3Athens Red Cross Hospital, Athens, Greece; 4Ealing Hospital NHS Trust, London, England; 5Department of
Epidemiology & Public Health, University College London, London, England; 6Department of Mathematics, National Technical University of Athens,
Athens, Greece; 7University of Athens Medical School, Athens, Greece; and 8Department of Cytopathology, University of Athens Medical School,
“Attikon” University Hospital, Athens, Greece.
Key Words: Invasive breast carcinoma grading; MIB-1 (Ki-67) immunohistochemistry; Automation; Survival; Nottingham Prognostic Index
Am J Clin Pathol December 2015;144:837-843
DOI: 10.1309/AJCPVH6FED2ZATUP
ABSTRACT
Objectives: For patients with invasive breast cancer,
management decisions are informed by tumor grade
according to the Nottingham Grading System (NGS), either
on its own or as part of the Nottingham Prognostic Index
(NPI). A system retaining the nuclear grade element but
substituting the two subjective components, mitosis count and
tubule formation, of the NGS with a proliferation index based
on Ki-67 (MIB-1) has been proposed (nuclear grade plus
proliferation [N+P] grading).
Methods: We validated the prognostic value of this grading
system on a population of 322 women.
Results: N+P grading resulted in more grade I tumors
(47.9% vs 4.5%) and fewer grade II (32% vs 51.5%) and
grade III (20.1% vs 44%) tumors compared with NGS.
The NPI calculated based on N+P grade had a similar
association with survival (P < .001; odds ratio, 1.729) as
the NPI calculated on the basis of the NGS grade (P < .001;
odds ratio, 1.668).
Conclusions: The N+P system seems equivalent to the NGS
system.
© American Society for Clinical Pathology
Therapeutic decisions in patients with breast cancer
largely depend on their classification in a manner that predicts their biology: clinical staging (American Joint Committee on Cancer TNM stages I-IV1), histologic grading
(1-32), and molecular biomarker-based classifications (estrogen receptor [ER],3 progesterone receptor [PR],4 human epidermal growth factor receptor 2 [HER2] gene,5 and recently
multigene prognostic indices6,7).
Histologic grading of breast cancer is commonly done
according to the Nottingham (Elston-Ellis) modification of
the Scarff, Bloom, and Richardson grading system,8 also
known as the Nottingham Grading System (NGS). In the
past, concerns over reproducibility of grading systems have
led to reluctance to use grades to aid therapeutic decisions.9
In 2007, Tawfik et al10 introduced the nuclear grade plus
proliferation (N+P) grading system, a more objective grading system that is claimed to better represent breast cancer
biology.
The N+P grade substitutes MIB-1 count for tubule formation and mitotic count, with the percentage of the total
number of breast cancer cells with nuclear staining classified
into three categories: 9% or less, 10% to 25%, and more than
25%, respectively. N+P grade I is defined as a tumor having
nuclear grade 1 or 2 and MIB-1 25% or less. N+P grade II
refers to a tumor with nuclear grade 3 and MIB-1 25% or
less, or nuclear grade 1 or 2 with a MIB-1 more than 25%.
N+P grade III describes a tumor having a nuclear grade 3
and MIB-1 more than 25%.
The initial results with the N+P grading system showed
that it is precise, reliable, and easy to use. MIB-1 assessment
Am J Clin Pathol 2015;144:837-843837
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Papadimitriou et al / N+P Grading for Breast Cancer
has been shown to outperform mitotic count in interobserver
agreement in other cancers.11 Nonetheless, the inventors
of the system did not test whether the N+P grading system
might confer additional prognostic information on patient
survival when tumor size or lymph node status is taken into
account—parameters used to determine prognosis in the
Nottingham Prognostic Index (NPI). N+P also has not been
evaluated with regard to the prognostic information it confers on disease-free survival.
The present study sought to compare the additional
prognostic information that the N+P grading system may
confer over the NGS when other relevant clinical parameters
are taken into account. It also sought to establish whether
the N+P grading system is valid in predicting disease-free
survival, as well as overall survival.
Materials and Methods
Patient Cohort
This was a retrospective study. After obtaining institutional board ethics approval (13/22-10-2010), we reviewed
medical records of 322 patients treated surgically for breast
cancer, from 2003 to 2007, in the Greek tertiary hospital
“Elena.” These included pathology reports and complete
follow-up records. Completion date for the follow-up of
all patients was February 28, 2011. Complete data were
available for 319 patients, and these were analyzed further.
Median follow-up was 65 months (minimum: 7 months;
maximum: 97 months).
Collection of pathology specimens was according to
institutional protocol: briefly, mastectomy and wide local
excision specimens were formalin fixed in 10% formalin
after the surgical procedure. Following paraffin embedding,
the tumor specimens were examined by H&E staining. All
specimens were evaluated by two consultant pathologists
(J.G.P. and P.K.) who reached consensus on tumor grading
according to the Nottingham modification of the ScarffBloom-Richardson grading system.
Immunohistochemistry
Tissue blocks containing representative tumor areas
were selected for immunohistochemistry (IHC). IHC was
performed on tissue fixed with 10% neutral buffered formalin. Paraffin-embedded tissue blocks were cut to 5-μm sections, deparaffinized in xylene, treated with 100% ethanol,
and heat treated in a microwave (0.01 M citrate buffer, pH
6.0 for 15 minutes) for antigen retrieval. Hormone receptors
(estrogen, progesterone), Her-2/neu, and Ki-67 (MIB-1)
were examined on all specimens using a DAKO Autostainer (DAKO, Carpinteria, CA) and commercially available
monoclonal antibodies ❚Table 1❚. ER and PR were graded
838 Am J Clin Pathol 2015;144:837-843
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❚Table 1❚
Protocols for Immunohistochemistry
Antibody
Vendor
Clone
Titer
ER
PR
HER2/neu
Ki-67
DAKO, Glostrup, Denmark
DAKO, Glostrup, Denmark
DAKO, Glostrup, Denmark
DAKO, Glostrup, Denmark
1D5
PgR 636
A0485
MIB-1
1:300
1:400
1:400
1:60
ER, estrogen receptor; HER2, human epidermal growth factor receptor 2; PR,
progesterone receptor.
as positive if more than 10% of the tumor cells exhibited
nuclear overexpression. HER2/neu was evaluated based on
the scoring guidelines of DAKO; scores of 0 and 1+ were
considered negative, and 2+ and 3+ were considered positive. At least three sections per tumor were examined. Ki-67
proliferation index was measured using the CAS-200 image
analyzer (Becton-Dickinson, San Jose, CA). An average
score of 10 areas with the highest staining intensity from
each specific lesion was calculated quantitatively using the
PI program of the image analyzer.
Subtypes
We evaluated tumor subtypes using an accepted histologic classification,12 classifying ER+ or PR+, HER2– as
luminal A; ER+ or PR+, HER2+ as luminal B; ER–, PR–,
HER2+ as HER2 overexpressing; and ER–, PR–, HER2– as
triple negative.
Prognostic Indices
NPI was calculated using the original formula13: NPI
= [0.2 × tumor size in cm] + [number of lymph nodes
involved: 0 = 1, 1-3 = 2, >3 = 3] + [grade of tumor], where
grade was either the NGS or N+P grade. We used the NPI to
stratify our patients into three groups: good prognosis (NPI
≤3.4), moderate prognosis (NPI 3.41-5.4), or poor prognosis
(NPI >5.4).
Statistical Analysis
We constructed a database wherein the following
parameters were included: age, type of surgery (mastectomy
or wide local excision), date of operation, ER and PR status, ErbB-2 (HER2) status, tumor size (measured on gross
pathologic examination), number of lymph nodes, histologic
grade, nuclear grade, Ki-67 staining (percent and classification), history of familial breast cancer, adjuvant chemotherapy, adjuvant hormonal therapy, relapse, chemotherapy
treatment on relapse, death, and total length of follow-up.
We incorporated the three variables: tumor size, number of
lymph nodes, and histologic grade in the NPI.
All statistical analysis was performed on SPSS version
22.0 (SPSS, Chicago, IL). We performed univariate Cox
analysis of all variables to find which of the parameters in
our database could be included in our model and, following
© American Society for Clinical Pathology
AJCP / Original Article
❚Table 2❚
Characteristics of Patients (n = 319)a
❚Table 3❚
N+P vs NGS Grade and NPI Scores (n = 319)a
Characteristic
Value
Characteristic
Age, mean (SD), y
Female sex
Family history
Yes
No
Operation type
Wide local excision
Mastectomy
Unknown
Tumor size, median (IQR), mm
Lymph nodes
0
1-3
>3
Ki-67 (MIB-1)
≤9%
10%-25%
>25%
ER
Positive
Negative
PR
Positive
Negative
HER2
Positive
Negative
Tumor subtypes
Luminal A (ER+ or PR+, HER2–)
Luminal B (ER+ or PR+, HER2+)
HER2 overexpressing (ER–, PR–, HER2+)
Triple negative (ER–, PR–, HER2–)
Adjuvant treatment
Chemotherapy
Hormone therapy
61.1 (11.6)
319 (100)
Tumor grade
I
II
III
NPI, mean (SD)
NPI prognosis
Good
Moderate
Poor
49 (15.4)
270 (84.6)
167 (52.4)
148 (46.4)
4 (1.3)
22 (16-30)
138 (43.3)
107 (33.5)
74 (23.2)
78 (24.5)
155 (48.6)
86 (27.0)
237 (74.3)
82 (25.7)
213 (66.8)
106 (33.2)
108 (33.9)
211 (66.1)
177 (55.5)
79 (24.8)
29 (9.1)
34 (10.7)
302 (94.7)
265 (83.1)
ER, estrogen receptor; HER2, human epidermal growth factor receptor 2; IQR,
interquartile range; PR, progesterone receptor.
a Values are presented as number (%) unless otherwise indicated.
that, built multivariate Cox analysis models both for overall
survival and disease-free survival. Our analysis compares
the NPI using the NGS grading system and the NPI using the
N+P grading system in a unique patient cohort.
Results
After reviewing the database, 319 patients, all female,
were included in the analysis due to missing data on three
patients. Patient demographics are presented in ❚Table 2❚.
Importantly, more patients in our cohort underwent breastconserving surgery than mastectomy (52.4%), and most
(68.7%) were placed in the moderate prognosis group
according to the NPI. Of the patients, 74.3% were ER
positive, 66.8% were PR positive, and 33.9% were HER2
positive. Most patients had adjuvant chemotherapy (94.7%)
and hormone therapy (83.1%). The anti-HER2 antibody
© American Society for Clinical Pathology
NGS
N+P
13 (4.1)
163 (51.1)
143 (44.8)
4.72 (1.19)
149 (46.7)
108 (33.9)
62 (19.4)
4.04 (1.28)
6 (1.9)
219 (68.7)
94 (29.5)
40 (12.5)
222 (69.6)
57 (17.9)
NGS, Nottingham Grading System; N+P, nuclear grade + proliferation grading
system; NPI, Nottingham Prognostic Index.
a Values are presented as number (%) unless otherwise indicated.
❚Table 4❚
Outcomes (n = 319)a
Characteristic
Value
Disease-free survival at end of follow-up
Overall survival at end of follow-up
Total follow-up, mean (SD), mo
Disease-free survival follow-up, mean (SD), mo
Recurrence
Local
Contralateral breast
Regional lymph nodes
Distant metastases
236 (74.0)
284 (89.0)
65.7 (17.2)
60.7 (21.6)
a Values
6 (1.9)
7 (2.2)
5 (1.6)
64 (20.1)
are presented as number (%) unless otherwise indicated.
trastuzumab (Herceptin) was not available for treatment of
primary breast cancer in Greece during that period.
The Ki-67 (MIB-1) proliferation index split patients
into three groups: 9% or less (24.5%), 10% to 25% (48.6%),
and more than 25% (27.0%). We used these data and nuclear
grade to calculate the N+P score for all patients in our cohort
and the equivalent NPI, and we compare our findings with
the standard NGS grading in ❚Table 3❚. Although the two
systems gave similar results for grade and prognostic index,
more patients were placed in the good prognosis group using
the N+P score (12.5% vs 1.9%), corresponding to more
grade I tumors (47.9% vs 4.5%) and less grade II (32% vs
51.5%) and grade III (20.1% vs 44%) tumors.
The importance of prognostic indices is their correlation with patient survival and recurrence (ie, prediction of
outcomes) ❚Table 4❚. At the end of follow-up (median, 65
months), 284 (89.0%) patients were still alive, and 236
(74.0%) patients were disease free. There were six cases
of local recurrence, seven recurrences in the contralateral
breast, five in the regional lymph nodes, and 64 instances of
metastatic disease.
We performed univariate Cox regression to evaluate the
effect of patient-specific, disease-specific, and treatmentspecific factors on survival and recurrence ❚Table 5❚.
Age (better prognosis with older age, P = .018), ER (better prognosis with positive ER, P = .003), PR (better prognosis
Am J Clin Pathol 2015;144:837-843839
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Papadimitriou et al / N+P Grading for Breast Cancer
❚Table 5❚
Univariate Cox Regression for Survival and Recurrence
Overall Survival
Disease-Free Survival
Characteristic
P Value
OR (95% CI)
P Value
OR (95% CI)
Age, y
Family history
Type of surgery
ER status
PR status
HER2 status
Tumor size, mm
No. of positive lymph nodes
Lymph node stage
1
2
3
Grade (NGS)
1
2
3
Nuclear grade
1
2
3
Ki-67, %
Ki-67 (MIB-1)
1
2
3
Grade (N+P)
1
2
3
NPI (NGS)
NPI (NGS) groups
NPI (N+P)
NPI (N+P) groups
Subtype classification
Luminal A
Luminal B
HER2+
TN
Adjuvant chemotherapy
Adjuvant hormone therapy
.018
.725
.154
.003
.004
.780
.036
.015
0.965 (0.936-0.994)
1.185 (0.459-3.057)
0.614 (0.314-1.200)
2.697 (1.389-5.238)
2.697 (1.381-5.270)
0.905 (0.450-1.823)
1.018 (1.001-1.036)
1.049 (1.009-1.091)
.261
.162
.667
.053
.191
.529
.137
.011
0.989 (0.970-1.008)
1.642 (0.820-3.287)
0.908 (0.584-1.411)
1.580 (0.993-2.512)
1.350 (0.861-2.118)
1.166 (0.723-1.882)
1.010 (0.997-1.024)
1.038 (1.009-1.068)
.012
1
2.175 (0.902-5.249)
3.579 (1.501-8.534)
.014
1
0.884 (0.508-1.538)
1.908 (1.149-3.166)
.039
0
0.506 (0.255-1.004)
1
.004
0.223 (0.031-1.616)
0.506 (0.323-0.794)
1
.082
0
0.528 (0.266-1.048)
1
1.772 (0.302-10.402)
.006
0.420 (0.102-1.728)
0.496 (0.313-0.785)
1
1.505 (0.451-5.020)
.017
0.646 (0.285-1.465)
0.331 (0.150-0.729)
1
.073
0.679 (0.380-1.212)
0.563 (0.341-0.931)
1
.006
0.314 (0.143-0.692)
0.401 (0.178-0.903)
1
1.668 (1.264-2.200)
0.374 (0.193-0.725)
1.729 (1.326-2.256)
0.285 (0.145-0.562)
.002
0.391 (0.227-0.674)
0.595 (0.347-1.020)
1
1.385 (1.155-1.662)
0.541 (0.346-0.844)
1.399 (1.177-1.662)
0.447 (0.275-0.725)
.525
<.001
.002
<.001
<.001
.006
.474
.007
0.367 (0.156-0.867)
0.293 (0.096-0.898)
1.155 (0.418-3.192)
1
0.483 (0.066-3.533)
2.597 (1.291-5.220)
.505
<.001
.006
<.001
.001
.037
.211
.061
0.829 (0.418-1.643)
0.484 (0.209-1.121)
1.507 (0.651-3.492)
1
0.408 (0.100-1.661)
1.638 (0.978-2.742)
CI, confidence interval; ER, estrogen receptor; HER2, human epidermal growth factor receptor 2; NGS, Nottingham Grading System; N+P, nuclear grade + proliferation; NPI,
Nottingham Prognostic Index; OR, odds ratio; PR, progesterone receptor; TN, triple negative.
with positive PR, P = .004), tumor size (better prognosis with
smaller tumor size, P = .036), number of positive lymph nodes
(better prognosis with less involved lymph nodes, P = .015),
lymph node stage (P = .012), tumor grade calculated with the
NGS system (better prognosis with lower grade, P = .039),
Ki-67 (MIB-1 classes) (P = .017), tumor grade calculated
with the N+P system (better prognosis with lower grade, P
= .006), NPI calculated with the NGS grade (P < .001), NPI
calculated with the N+P grade (P < .001), prognostic groups
defined by the NPI calculated with the NGS grade (P = .002),
prognostic groups defined by the NPI calculated with the N+P
grade (better prognosis with smaller scores, P < .001), IHCdefined subtypes (from better to worse prognosis: luminal B,
840 Am J Clin Pathol 2015;144:837-843
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luminal A, triple negative, HER2 overexpressing, P = .011),
and adjuvant hormone treatment (better prognosis for those
who received hormone treatment, P = .007) were statistically
significant factors affecting survival.
Number of positive lymph nodes (P = .011), lymph
node stage (P = .014), tumor grade (NGS) (P = .004),
nuclear grade (P = .006), tumor grade (N+P) (P = .002), NPI
(NGS) (P < .001), NPI (NGS) groups (P = .006), NPI (N+P)
(P < .001), NPI (N+P) groups (P = .001), and IHC-defined
subtype classification (P = .037) were statistically significant factors affecting recurrence.
We found that the N+P-based NPI is not inferior to the
NGS-based NPI in defining prognostic groups.
© American Society for Clinical Pathology
AJCP / Original Article
❚Table 6❚
Multivariate Cox Regression for OS and DFS Models
NGS Model
Characteristic
OS
Age, y
ER status
PR status
NPI (categ)
DFS
Subtype
Luminal A
Luminal B
HER2+
TN
NPI (categ)
N+P Models
P Value
OR (95% CI )
P Value
OR (95% CI)
.028
.425
.025
.008
0.966 (0.936-0.996)
1.387 (0.621-3.100)
2.500 (1.119-5.584)
0.401 (0.205-0.786)
.035
.521
.040
.005
0.967 (0.937-0.998)
1.304 (0.579-2.939)
2.306 (1.038-5.127)
0.365 (0.181-0.737)
.035
.006
.058
0.829 (0.418-1.641)
0.463 (0.200-1.073)
1.501 (0.648-3.477)
1
0.536 (0.344-0.835)
0.911 (0.459-1.809)
0.497 (0.214-1.153)
1.504 (0.649-3.485)
1
0.458 (0.281-0.746)
.002
CI, confidence interval; DFS, disease-free survival; ER, estrogen receptor; HER2, human epidermal growth factor receptor 2; NGS, Nottingham Grading System; N+P, nuclear
grade + proliferation; NPI (categ), Nottingham Prognostic Index categories: good/moderate vs poor; OR, odds ratio; OS, overall survival; PR, progesterone receptor; TN, triple
negative.
100
Good or moderate
95
Poor
90
85
80
0
20
40
60
Cumulative Survival (%)
Cumulative Survival (%)
100
80
90
Good or moderate
80
70
Poor
60
50
0
20 40 60 80 100
Disease-Free Survival (mo)
Overall Survival (mo)
❚Figure 1❚ Cox regression. Overall survival according to
Nottingham Prognostic Index (nuclear grade plus proliferation)
prognostic category.
❚Figure 2❚ Cox regression. Disease-free survival according to
Nottingham Prognostic Index (nuclear grade plus proliferation)
prognostic category.
Multivariate Cox regression was performed using statistically significant variables and removing variables that
derive from others and create problems of multicollinearity.
Thus, we selected age, ER status, PR status, and the relevant
NPI for comparisons ❚Table 6❚. The prognostic indices retain
their statistical significance in the multivariate models. The
value of prognostic indices in the clinic is in guiding management decisions for adjuvant chemotherapy and frequency
of outpatient follow-up; in this respect, the N+P NPI model
proves slightly superior to the NGS NPI model, clearly
separating good and moderate prognosis patients from poor
prognosis ones both for overall and disease-free survival
❚Figure 1❚ and ❚Figure 2❚.
Joint Committee on Cancer Staging manual, the European
Union, and the Royal College of Pathologists. It assigns a
score of 1 to 3 each to tubule formation (>75% = 1, 10%75% = 2, <10% = 3, commonly abbreviated as T), nuclear
pleomorphism (an indicator of cellular differentiation; small
regular uniform cells = 1, moderate nuclear size and variation = 2, marked nuclear variation = 3, commonly abbreviated as N), and mitotic activity (an indicator of proliferation;
with 0-9 mitoses/high-power field [hpf] = 1, 10-19 mitoses/
hpf = 2, >20 mitoses/hpf = 3, commonly abbreviated as
M). A tumor with a total score of 3 to 5 is categorized as
grade 1, one with a score of 6 or 7 as grade 2, and one with
a score of 8 or 9 as grade 3. This system is reported to have
significant interobserver agreement and correlates well with
both disease-free and overall survival. At 10-year follow-up,
grade 1 cancers are expected to have 85% survival, grade 2
about 60%, and grade 3 only 45%.
The NGS has a modest degree of reproducibility,14
although continuous standardization efforts have led to
Discussion
The NGS is endorsed by the World Health Organization, the College of American Pathologists, the American
© American Society for Clinical Pathology
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Papadimitriou et al / N+P Grading for Breast Cancer
better results over time. Nonetheless, histologic grade is and
remains a partially subjective parameter. Thus arises the
need for a more objective grading system that is easier to use
at the same time: the N+P system.
Antigen Ki-67 is a cellular marker for proliferation.
Ki-67, a nonhistone protein, is expressed in proliferating cells
through all active phases of the cell cycle (G1, G2, S, M) but
is absent from resting cells (G0). Several antibodies against
Ki-67 have been assessed, the most commonly used being
MIB-1 (DAKO), which, unlike the original Ki-67 antibody,
can be used on formalin-fixed, paraffin-embedded tissue.15
Measurement of Ki-67 and receptor status by image
analysis is widely reported in the literature16,17 and has
been shown to closely correlate with visual analysis.11,18
The advantage of automated, quantitative methods such
as the CAS-200 is their objectivity and speed.19 Assessment of Ki-67 and other immunohistochemical markers by
automated systems has known weaknesses. Interobserver
agreement as low as 56% has been reported,20 and there is
controversy over Ki-67 assessment by both image analysis
and visual inspection.21 Even though CAS-200 is an image
analysis system developed in the 1980s and there are newer,
possibly more accurate, methods available or under development today,22 it remains in use in a variety of institutions.
Ki-67 has been assessed as a prognostic factor in a
number of studies,23-27 but it is not part of routine clinical
evaluation in breast cancer.28 There is evidence that wellestablished immunohistochemical markers (ER, PR, HER2,
Ki-67) combining hormone receptors with a proliferation
index (the IHC4 score) could confer similar prognostic
information to the 21-gene Genomic Health recurrence
score (GHI-RS, also known as Oncotype DX) at a fraction
of the cost.29 The cutoff points for Ki-67 used in our study
and previously suggested by Tawfik et al10 are far from
universal, and more research is needed to evaluate these as
prognostic markers. To date, this is the largest patient series
from Greece evaluating Ki-67 and derived indexes in breast
cancer prognosis. Strengths of our study include population
homogeneity since our cohort comes from a single tertiary
hospital in a relatively short period of 4 years, no losses
to follow-up, and robust, consistent laboratory methods
in the assessment of biomarkers from a single university
laboratory.
Our study has several weaknesses. It is a cohort study
and is subject to inherent bias since patient management
is not rigorously controlled as in a clinical trial. Apparent
indicators of this are that most (95%) of our patients had
adjuvant chemotherapy. There is controversy over Ki-67
assessment by both image analysis and visual inspection21;
our study did not include a comparison of the automated
evaluation with visual assessment. Data collection, although
prospective, did not include factors that may have influenced
842 Am J Clin Pathol 2015;144:837-843
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outcomes—namely, type of chemotherapy regimens and
adjuvant radiotherapy. Our follow-up period, although
greater than 5 years on average, may be considered short for
breast cancer, a disease with an excellent outcome with current treatment modalities; in fact, our series has 89% overall
survival and 74% disease-free survival. We encourage additional prospective study of a more controlled patient group.
In conclusion, we have demonstrated the N+P system to
be equivalent to the traditional NGS system in the grading of
breast cancer in a Greek patient cohort, both as an individual
predictor and as part of the NPI. At the same time, the N+P
system is simpler and easier to use.
Corresponding author: Sarantos Kaptanis, MD, JD, Centre for
Tumour Biology, Barts Cancer Institute, Queen Mary, University
of London, John Vane Science Centre, Charterhouse Square,
London EC1M 6BQ, UK; [email protected].
This research received institutional board ethics approval from
the University of Athens (13/22-10-2010) and was supported by
Greek tertiary hospital “Elena.”
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Am J Clin Pathol 2015;144:837-843843
DOI: 10.1309/AJCPVH6FED2ZATUP