Semi-quantitative scoring of potentially predictive markers for endocrine treatment of breast cancer: a comparison between whole sections and tissue microarrays

Abstract

Aim: To assess whether immunohistochemically stained tissue microarrays (TMA) of 2 mm cores from paraffin embedded tumour tissue may replace whole sections in semi-quantitative evaluation of selected potential markers for endocrine treatment. Methods: Whole sections and 2 mm cores on TMA were used for immunohistochemical staining of potential markers for endocrine treatment. The Allred scoring system was used for the markers with nuclear localisation: the oestrogen receptor, the progesterone receptor, p27 and the oestrogen receptor co-regulator amplified in breast cancer 1 (AIB1). The Allred scoring system was also used for the non-nuclear markers Bcl-2, pS2 and cyclooxygenase 2 (COX-2); the membrane receptors HER-2, insulin-like growth factor I receptor (IGF-IR) and epidermal growth factor receptor were quantified according to the guidelines for the Herceptest. Results: The data and statistical analyses showed that the semi-quantitative evaluation of oestrogen receptor, progesterone receptor, AIB1, COX-2, HER-2 and IGF-IR on TMA blocks was comparable with analysis on whole sections. Conclusions: This study shows that semi-quantitative scoring of 2 mm cores on TMA is feasible for several potential markers for endocrine therapy. Considering the small size of many breast tumours, the speed and cost-effectiveness of immunohistochemistry on TMA compared with whole sections, and the importance of the expression level of the proteins, semi-quantitative scoring on TMA has great potential in both retrospective and prospective studies aiming at improving the prediction of response to endocrine treatment.

An ER activity profile including ER, PR, Bcl-2 and IGF-IR may have potential as selection criterion for letrozole or tamoxifen treatment of patients with advanced breast cancer

“…Staining of the IGF-IR had the same appearance as e.g. HER-2 staining, except that IGF-IR, as previously described was also often seen in the cytoplasm [22]. IGF-IR scoring values of 2' and 3' were observed in 28% and 32% of the samples, respectively.…”

“…Kidney tissue was placed in the first core of the upper left and right corner of the TMA block to ensure correct orientation when examining the slides. All analyses were performed with the use of TMAs, allowing semi-quantitative analysis [21,22].…”

“…TMAs allow rapid, cost-effective and standardized analyses with the use of only a small amount of paraffin embedded tumor tissue and it has made immunohistochemical characterization of protein expression in large series of tumors easier and less laborious [21]. Furthermore, TMAs can be used for semi-quantitative analysis of various potential predictive marker proteins [22].…”

Interaction between cyclooxygenase-2 and insulin-like growth factor in breast cancer: A new field for prevention and treatment

“…This finding is consistent with that of Henriksen et al (47), who, by using the semi-quantitative method as recommended by the HercepTest (quantifying their results in scores 0, 1, 2 and 3), found a positive correlation between COX-2 and IGF1-R (p<0.01).…”

Epidermal growth factor receptor (EGFR) and the estrogen receptor modulator amplified in breast cancer (AIB1) for predicting clinical outcome after adjuvant tamoxifen in breast cancer

“…The inverse relationship between ER and EGFR contributing to a very small fraction of ER positive and EGFR positive tumours is speculated to be one explanation to the findings (8,9) as well as non-standardised methods of analysis using different antibodies and protocols. It should also be mentioned that we have analyzed EGFR and AIB1 on tissue microarray, which in a study by Henriksen and co-workers were comparable to the analyses on whole sections [22]. EGFR has been found to be associated with an aggressive tumour type having prognostic value in clinical studies, including cohorts of patients treated with adjuvant chemotherapy [23][24][25].…”