Molecular Pathology of Breast Cancer

Ian Ellis Molecular Medical Sciences, University of Nottingham Departments of Histopathology, Nottingham City Hospital NHS Trust

Time

Prognosis

Intrinsic

Time

Prognosis

How long the tumour has been there Stage

Intrinsic The nature of the tumour Biology

Nottingham Prognostic Index Grade + LN Stage + (0.2 x Size) 1-3

1-3

cm

Nottingham Prognostic Index 100

Age matched

% Survival

80

GPG (2.1=3.4)

60

MPG (3.41-5.4)

40

20

PPG (>5.4) 0 0 635 1040 316

2

4

6 237 357 39

8

10

12

14

46 63 7

GPG MPG PPG

16

18

Years

Histological Grade in Breast Carcinoma Consistency and Reproducibility Poor Cutler et al

1966

Stenkvist et al

1979

Delides et al

1980

Gilchrist et al

1985

Histological Grade in Breast Cancer Tubule formation Majority of tumour Moderate degree Little or none

(>75%) (10-75%) (20

>11

>23

* Assessed as number of mitoses per 10 fields at the tumour periphery

Nottingham Method for Histological Grade in Breast Carcinoma

Consistency and Reproducibility Satisfactory Dalton et al

1984

Frierson et al

1985

Robbins et al

1995

Nottingham Method for Histological Grade in Breast Carcinoma Recommended by: RCPath NHSBSP EU AJCC UICC WHO

Cox Multivariate Analysis Size Grade Tumour type LN Stage Vascular Invasion

??? 0.19 0.64 0.29 0.76 0.18

Z values > 1.96 significant at p=0.05 level

Z 4.86 6.69 3.47 11.18 3.18

Cum. Survival

N P I 1

.8 EPG GPG

.6

MPG I MPG II

.4

.2

PPG

Chi-Square 899.005

DF P-Value 4 1.96 significant at p=0.05 level

?Z 2.93 5.64 6.96 1.46 1.78 1.21 0.11 1.27 1.26

Cox Multivariate Analysis

Size Grade LN Stage Tumour type Vascular Invasion ER C-erb-B2 DNA Index Proliferation Index

? 0.17 0.86 0.81 0.31 0.19 0.001 0.02 0.28 0.17

Z values > 1.96 significant at p=0.05 level

?Z 2.93 5.64 6.96 1.46 1.78 1.21 0.11 1.27 1.26

Prognostic Factors but eliminated by multivariate analysis Receptors & related ER PR Bcl-2 Liv-1 PS2 Cap D Histological Angiogenesis LVI Type Nucleolar Organisers

Cell Antigens Lectins CEA Epithelial memb. Ag Growth Factors EGFR Cerb-B2/3&4 Proliferation Markers Mib1 Ki67 TK S-Phase

Oncogenes C-myc Suppressor genes P53 Adhesion molecules E-Cadherin Catenins Integrins Cell Antigens

Do we really need prognostic factors for breast carcinoma? There are at least three situations in which prognostic factors could be helpful • To identify patients whose prognosis is so good that adjuvant therapy after local surgery would not be cost beneficial

•

To identify patients whose prognosis is so poor that a more aggressive adjuvant approach would be warranted

•

To identify patients likely to be responsive or resistant to particular forms of therapy

Clark GM. Breast Cancer Res Treat. 1994;30:117-26

Cum. Survival

N P I 1

.8 EPG GPG

.6

MPG I MPG II

.4

.2

PPG

Chi-Square 899.005

DF P-Value 4