Shimizu et al. (2000)

Shimizu et al. (2000)
Design: Retrospective case series (other), evidence level: 3
Country: Japan
Inclusion criteria:
None stated
Exclusion criteria:
None stated
Number of patients = 21, age range 35 to 75 years, mean age = 50 years.
Paired samples from primary and metastatic tumour tissues were processed for determination of Her2 protein by IHC (n = 17) and immunoassay (n = 4).

Her2 protein overexpression was determined by means of IHC on paraffin embedded samples. The primary antiserum was rabbit anti-c-erbB-2 polyclonal antibody (Nicherei).

Her2 protein expression was scored by criteria set by Tsuda et al 1990 - based on the intensity of staining of the cell membrane as being either strong (and hence positive) or weak with cytoplasmic staining (negative).

Her2 protein was measured in four patients by standard sandwich enzyme immunoassay, using the same antisera as that used for IHC. Her2 status was deemed positive at above 18 ng per ml of protein.

Immunoassay was used to measure the expression of both PR and ER. Values above 10 fmol per mg of protein (ER) and 13 fmol per mg of protein (PR) were graded as positive.
Quantitative analysis of the degree of Her2 overexpression was carried out on each paired set of samples to assess any changes between primary and recurrent or metastatic tumours.
Follow up:
Histological grade of tumour (n=21):
Grade I (least aggressive) = 9.5%
Grade II (intermediate) = 19%
Grade III (most aggressive) = 71.5%

T-stage (n=21):
T1 (< 2cm) = 14%
T2 (2–5cm) = 62%
T3 (> 5cm) = 14%
T4 (extensive) = 10%

Concordance between primary and metastatic samples (Her2):
Primary: +ve (n = 8) metastasis: (n = 8)
Primary: −ve (n = 13) metastasis: (n = 13) (nsd)

Concordance between primary and metastatic samples (ER n=20):
Primary: +ve (n = 10) metastasis: (n = 5)
Primary: −ve (n = 10) metastasis: (n = 15) (P = 0.19 = nsd)

Concordance between primary and metastatic samples (PR n=20):
Primary: +ve (n = 12) metastasis: (n = 6)
Primary: −ve (n = 8) metastasis: (n = 14) (P = 0.11 nsd)
General comments:
This paper describes a small retrospective case series of patients who had had both primary and asynchronous metastatic lesions removed and analysed for expression of Her2, PR and ER. Patients had undergone surgery between April 1996 and September 1998.

Her2 status appears not to have changes between primary and metastatic lesion (mostly locoregional) and the hormones receptors show a non-significant reduction with disease progression.

Interestingly, of the 8 patients showing changes to either ER and/or PR status, 3 had received hormone therapy as adjuvant therapy but 5 patients had received no adjuvant therapy.

Although a reasonable study, the low patient numbers reduce the statistical strength.

From: Chapter 2, Presentation and diagnosis

Cover of Advanced Breast Cancer
Advanced Breast Cancer: Diagnosis and Treatment.
NICE Clinical Guidelines, No. 81.
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