P5-11-06: Immunohistochemistry Discordance between Primary and Recurrent Tumors in Breat Cancer. Analysis of Potential Influence of Technique Bias by Comparing Test-Results under Two Different Conditions.
Authors: Perez-Fidalgo J-A , Ferrer J , Bosch A , Burgués O , Martinez M , Eroles P , Bermejo B , Pons V , Lluch A 
Published: June 2012

Introduction: Discordance in expression of estrogen (ER) or progesterone receptors (PgR) and HER2 has been previously described in several studies, having this discordance an important impact on therapeutic approach or even in survival. However it is unclear whether discordance is a reflex of a clonal differentiation to a more aggressive biological tumour or the consequence of technical biases or inter-explorer variability. We aimed to assess the role of technique biases in observed discordance between primary tumour (PT) and recurrent tumour (RT) by analyzing discordance in two different situations: routine versus optimal conditions.

Patients and methods: We conducted a retrospective study in patients (pts) diagnosed with a recurrent breast cancer in the Hospital Clinico of Valencia between January 2000 and June 2010. All patients had a previous histological diagnose of the PT and all underwent a second histological study of the RT. Discordance was assessed in terms of hormone-sensibility (HS) (any ER or PgR +) vs hormone-resistance (HR) (ER-/PgR -) and triple negativity (TN) (ER-, PgR-, HER2−) vs non-TN (any positive). Routine conditions were referred to the immunohistochemistry (IHC) assessment of the normal practice on the base of which therapeutic decisions were made. Routine conditions were performed in the Pathology Department of our institution but PT and RT were usually evaluated at different timing and ocasionally by different pathologists. In order to assess potential laboratory biases we repeated IHC analysis under optimal conditions. For these optimal conditions analyses, paired samples from both PT and RT were reassessed at the same time and tests were performed in the same way. Final determination of the results was made by two highly trained pathologists and in case of disagreement in any determination, both explorers re-assessed the sample at the same time.

We evaluated discordance between PT and RT under both conditions, and the accuracy of determinations in PT or RT between both conditions.

Results: 128 paired samples (from 64 different pts) were analysed. Median age of the series was 48.5 years (range 27–83). Recurrences were loco-regional in 14 pts (21.9%) and distant in 50 pts (78.1%). RT tissue was obtained from skin and soft-tissues in 18 pts (28.1%), lung in 11 (17.2%), bone in 10 (15.6%), lymph nodes in 10 (15.6%), pleura/peritoneum in 9 (14.1%) and liver in 6 (9.4%). Discordant cases between PT an RT in terms of HS/HR were 30.4% in routine conditions and 9.8% in optimal conditions. In terms of TN/non-TN were 14.3% in routine vs 8.2% in optimal conditions. Accuracy in results HS/HR between routine and optimal conditions was 80.7% in PT and 76.0% in RT. In results of TN/non-TN accuracy between both conditions was 94.2% in PT and 87.2% in RT.

Conclusions: Results suggest that an important rate of discordance observed in routine conditions might be strongly influenced by technique biases. However, changes observed in optimal conditions with 9.8% discordance in HS/HR and 8.2% in TN/non-TN suggest that in a small proportion of tumours, observed discordance might be explained by biological mechanisms.

Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P5-11-06.