Tapia et al. (2007)

Tapia et al. (2007)
Design: Retrospective case series, evidence level 3
Country: Switzerland
Inclusion criteria: None stated
Exclusion criteria: None stated
Number of patients = 105, age range 26 to 85 years, mean age = 58 years
Paired biopsy samples from a primary cancer and from distant metastases in each patient were processed for determination of Her2 gene expression by fluorescent in situ hybridisation (FISH). Additional sampling of lymph node metastases was undertaken in 31 women.
To determine the rate of discordance of Her2 status between primary and metastatic cancer tissue.
Follow up:
Metastases were located in ascites (n=3), liver (n=4), lung (n=9), lymph nodes (n=3), pericardium (n=1), pleura (n=74), skin or soft tissue (n=3) or CNS (n=8).

Her2 status of primary and metastatic sites was concordant in 92.4% of the 105 patient samples (κ = 0.76 95%CI: 0.61–0.92). When discordant pairs were re-examined this figure rose to 97.1% (κ = 0.85 95%CI: 0.73–0.98).

Her2 amplification occurred in 22/105 primary tumours and 21/105 paired distant metastases.

Her2 status differed from primary to metastases in 8/105 pairs. These 8 cases were re-analysed: Her2 − ve (primary) to +ve (metastases) change occurred in 2 patients and Her2 +ve (primary) to −ve (metastases) change occurred in 1 patient. All other discrepancies were explained on the basis of borderline scoring of tissue one way or the other and were resolved on re-examination.
General comments:
This paper describes a three centre study comparing the Her2 status of primary and metastatic tissue from women with breast cancer. The specimens were collected between 1999 and 2006. Tumour tissue was graded (nuclear grade I–III) by tissue micro-array and Her2 status was determined by FISH. The rate of concordance between paired tissue samples was analysed with the κ coefficient where a value of >0.8 was ‘excellent’ and 0.61–0.8 was ‘substantial’.

The authors point out that, on the basis of FISH analysis, discordance occurred in 7.6% of patients. Given that the level of re-investigation undertaken in this study would be unlikely to occur in a clinical situation, there could be a risk of both under- and over-treatment for some patients. Inconsistencies between the paired samples were generally due to interpretational differences rather than actual biological conversion by clonal selection or genetic drift during progression.

From: Chapter 2, Presentation and diagnosis

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