Subik K, Delaney A, Wang J, Wang X, Schiffhauer LM, Shayne M, Huston A, Skinner K, Hicks DG, Tang P. Recurrence score of 21-gene assay is correlated with a panel of immunopathological factors of breast cancer. Poster presented at the USCAP 99th Annual Meeting; February 2010. [abstract] Mod Pathol. 2010 Feb 1; 23:74A.

Background: We have previously reported that higher recurrence score (RS) of 21-gene assay (Oncotype DX) is strongly associated with progesterone receptor (PR) negative breast cancer. Here with a larger case number, we sought to investigate the relationship between RS and a panel of immunopathological features of breast carcinomas.

Design: We identified 77 infiltrating carcinomas (70 IDC and 7 ILC) that had 21-gene assay tested from our departmental file and analyzed the relationship between the RS and clinicopathological factors. Immunohistochemical analyses were performed for ER, PR, HER2, EGFR, CK5/6. ER and PR were recorded as Allred scores. HER2 was scored as positive if >30% of tumor cells showed 3+ membrane staining. EGFR was designated as positive if any tumor cells showed 1+ positive stain. Any strong cytoplasmic stain was considered as positive for CK5/6. The definitions for each molecular subtype were based on the expression of ER, HER2, EGFR and CK5/6.

Results: Among the 77 cases, 46 had low RS (0-17), 26 had intermediate RS (18-30), and 5 had high RS (>31). PR expression was inversely associated with RS, with the mean Allred scores =7.72, 6.35 and 2.00 in low, intermediate and high RS group, respectively (p<0.0001). RS was also significantly associated with tubal formation, mitosis and luminal B subtype. Based on our data, a regression equation = 17.489 + 2.071 (tubal formation) + 2.926 (mitosis) – 2.408 (PR) – 1.061 (HER2) + 7.051 (luminal A) + 29.172 (luminal B) predicted RS with an R2 of 0.65, which classified 59/77 cases into the same risk group as the assay RS. For the discrepancy between calculated RS and assay RS, 6 cases that had higher calculated RS compared to assay RS were tumors that were HER2 positive, high grade, or low PR expression; 12 cases that had lower calculated RS were tumors with high ER and PR expression, and low to intermediate histologic grades. The expression levels of PR and HER2 were also very important in the discrepancy between histologic grade and assay RS.

Conclusions: PR negativity, HER2 over-expression and high histologic grade are strongly correlated with a higher RS. More studies are needed to further investigate these relationships.

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