The HER2-scores for the analysed 47 primary tumours and the corresponding 47 lymph node metastases are shown in
. There were no changes between the primary tumours and the corresponding lymph node metastases in the majority of cases. Only seven changes were observed. There were six changes from 1+ to 0 and one change from 3+ to 2+ when the metastases were compared to the primary tumours. Only samples scored as 2+ or 3+ were gene amplified as seen from analyses with both FISH and CISH.
HER2-scores for the analysed primary tumours and the corresponding lymph node metastases (n=47)
The 10% cutoff level was applied. This means that only samples with more than 10% membrane-stained tumour cells were scored 1+, 2+ or 3+ in . However, the percentage positive tumour cells in all primary tumours and in all metastases were actually in the range 50–100%. Therefore, all cutoff levels below 50% give the same result as reported in .
The intensity in staining in the primary tumours was, in most cases, either strong (n=23) or there was no staining at all (n=13). There were not so many cases with intermediate staining intensity, faint staining (n=8) and moderate staining (n=3). This pattern was similar in the lymph node metastases, which had strong staining in 22 cases, moderate staining in four cases, faint staining in two cases and no staining in 19 cases.
The major results from the HER2-score analyses are summarised in
. It is clear that in the majority of cases, there were no changes between the primary tumours and the corresponding lymph node metastases with respect to HER2 overexpression. Examples of staining patterns for a primary tumour and the corresponding metastasis (which both were scored as 3+) are shown in .
Major results from the HER2-scores analyses (n=47)
Typical immunohistochemical HER2-stainings. A section from a primary breast tumour (A) and a section of a lymph node metastasis (B) from the same patient are shown. Both cases were scored 3+.
The literature was reviewed for recently published studies on HER2 expression in primary breast tumours and corresponding metastases (see
). Only studies from the last 4 years and in which HercepTest, or a similar immunohistochemical analysis, was applied were included. It is concluded that breast cancer lymph node metastases generally overexpress HER2 in a manner similar to the corresponding primary tumours. In two studies (Vincent-Salomon et al, 2002
; Gancberg et al, 2002
), distant metastases were also analysed, and the conclusion was that these also express HER2 as the primary tumours. These conclusions are also supported by previously published FISH studies (e.g. Thor, 2001
; Xu et al, 2002
Recent examples from the literature on HER2 expression in primary tumours and the corresponding metastases
The studies referred to in also showed that the similar scorings between the primary tumours and the corresponding metastases were not due to random changes so that a number of HER2 positive primary tumours that converted to HER2 negative metastases were balanced by a similar number of conversions in the other direction. Changes in HER2 expression actually seemed to be extremely rare, although a few cases were reported, and the general conclusion is that the HER2 expression is stable when the metastases are compared to the corresponding primary tumours.
It is noted that the percentage HER2 positive primary tumours and metastases were higher in the present study than in the previously published studies (). This is difficult to explain since the selections of patient materials were, as far as we know, random in all studies. However, it is possible that the tumours included in our study were, on the average, of more aggressive type than in the other studies. This is not possible for us to judge in detail since we do not have detailed gradings for the different studies (e.g. Elston scores). Our tumours were rather extensive since it is seen from that 37 tumours were classified as pT2–pT4 while only 10 were classified as pT1. The aggressive nature of our tumours also stems from the fact that all samples were drawn from patients with subsequent distant metastases. This probably gives a selection for high HER2-expressing tumours. For example, in one study it has been reported that 60% of the studied breast cancer bone marrow metastases were HER2 positive (Braun et al, 2001
). However, the aim of our study was to compare HER2 expression in primary tumours in relation to the corresponding metastases and for that the considered data are hopefully good enough in all the studies.