Comparison of prognostic values between combined immunohistochemical score of estrogen receptor, progesterone receptor, human epidermal growth factor receptor 2, Ki-67 and the corresponding gene expression score in breast cancer

Abstract

In the clinical diagnosis of breast cancer, immunohistochemistry panels with estrogen receptor (ER), progesterone receptor (PgR), human epidermal growth factor receptor 2 (HER2) and Ki-67 are routinely used, and they have been proposed for the classification of breast tumors into distinct subtypes. Gene expression analysis with formalin-fixed paraffin-embedded material have also become widely available recently, but the prognostic values of corresponding gene panels compared with these four immunohistochemical panels had never tested. We independently evaluated the 5-year relapse risk-estimation scores using semiquantitative data of four immunohistochemical panels (Ku-IHC4 score) and compared these with the results of four-gene expression profiling of formalin-fixed paraffin-embedded specimens (Ku-FFPE4 score) in a consecutive series of 235 primary invasive breast cancer patients. Ku-IHC4 score was revealed to be an independent predictor of recurrence other than Ku-FFPE4 score in a multivariate model analyzed by classical clinical parameters (Ku-IHC4 score vs Ku-FFPE4 score; v 2 : 14.2 vs 2.5, P: 0.0002 vs 0.11). When patients were trichotomized into high-, intermediate-and low-risk groups using the thresholds determined from the approximately calculated 5-year relapse rate, Kaplan-Meier analyses showed a significant difference among the three groups in Ku-IHC4 score (log-rank, Po0.0001), but not in Ku-FFPE4 score. The high-risk group according to Ku-FFPE4 score showed contradictory low recurrence rates (Ku-IHC4 score vs Ku-FFPE4 score, 53.1 vs 24.8%), which might be caused by risk-dependently extended error ranges. We show that the Ku-IHC4 score, consisted with semiquantitative measures of immunohistochemistry, provides better prognostic information than the corresponding quantitative RNA measurements. Prognostication tools such as the Ku-IHC4 score may be potentially useful in screening which patients had better be assessed by further testing using other genes rather than ER, PgR, HER2 and Ki-67 to determine critical aspects of therapeutic decision making.

Study of Metastasis in Lymphnode Biopsies with Special Reference to Immunohistochemistry (IHC) in Metastatic Breast Carcinoma

“…ER, PR and HER2/neu expression was negative in majority of cases which correlated with other Indian studies by Kuraparthy et al, [16] and Verma et al, [10]. International studies were showing hormone receptor positivity and HER2/neu negativity [11][12][13]. Immunohistochemical expression of lymph node metastasis from IDC cases were mainly ER, PR and HER2/neu negative.…”

“…In this study, out of 185 mastectomy specimen, 41.67% cases were associated with axillary lymph node metastasis. This correlated with other Indian and international studies [10][11][12][13][14][15]. In view of rising incidence of breast cancer in India, a thorough assessment of mastectomy and axillary lymph node biopsies is essential.…”

Adjuvant treatment recommendations for patients with ER-positive/HER2-negative early breast cancer by Swiss tumor boards using the 21-gene recurrence score (SAKK 26/10)

“…One study suggests that the amount of prognostic information contained in four widely performed immunohistochemical (IHC) assays is similar to that in a multi-gene test [35]. Moreover a study comparing several multi-gene tests to IHC4 (using semiquantitative assessment) showed that the IHC4 score provides better prognostic information than the corresponding quantitative RNA measurements [36]. Thus the combination of quality controlled conventional IHC tests and multigene signatures may provide more information for some patients at intermediate risk of relapse.…”

The Clinical Significance of CD169-Positive Lymph Node Macrophage in Patients with Breast Cancer

“…Normal mouse immunoglobulin (DAKO, Glostrup, Denmark) was used as a negative control and no signal was observed in those control sections. Data regarding the Ki-67 labeling index, as well as the statuses of ER, PgR, and Her2, were previously evaluated by our research group [19, 20]. CD68-, CD169-, and CD8-positive staining was counted in four randomly selected fields-of-view by two pathologists (TS and YM) who were blind to patient information.…”