Luminal A versus luminal B breast cancer: MammaTyper mRNA versus immunohistochemical subtyping with an emphasis on standardised Ki67 labelling‐based or mitotic activity index‐based proliferation assessment

Abstract

Aims: Proliferation assessment by the use of Ki67 is a crucial component in intrinsic subtyping of luminal breast cancers (BCs), but suffers from variability between laboratories, observers, and methods. Mam-maTyper is a quantitative molecular tool that measures mRNA levels of ERBB2, ESR1, PGR and MKI67 in BC, and interprets the results according to the St Gallen 2013 consensus recommendations. We compared MammaTyper with immunohistochemistry (IHC)-based subtypes, with a focus on standardised proliferation assessment. Methods and results: We analysed the agreement in assigning subtypes between MammaTyper and receptor IHC in 101 unifocal luminal HER2-negative early BCs of no special type. Two Ki67 counting protocols, Ki67-Global (Ki67-G) and Ki67-HotSpot (Ki67-H), recommended by the International Ki67 in BC Working Group, and the mitotic activity index (MAI) were used for proliferation assessment. The proportions of BCs identified as luminal A and as luminal B were 55% and 45% for MammaTyper, 55% and 45% for IHC + Ki67-G, 36% and 64% for IHC + Ki67-H, and 56% and 44% for IHC + MAI. The levels of agreement between MammaTyper-based and IHC-based subtyping were 84% (j = 0.679) for IHC + Ki67-G, 72% (j = 0.462) for IHC + Ki67-H, and 89% (j = 0.779) for IHC + MAI. Conclusions: High rates of agreement between mRNA-based and IHC-based intrinsic subtyping of luminal HER2-negative BC can be achieved. However, the agreement between IHC-based and MammaTyperbased luminal subtypes depends on the proliferation assessment method, and was highest when the MAI was used. Further comparative clinical studies are needed to determine which method is to be preferred, including analysis of cost-effectiveness.

Low correlation between Ki67 assessed by qRT-PCR in Oncotype Dx score and Ki67 assessed by Immunohistochemistry

“…Another study comparing microarray data with IHC confirm in a series of 520 samples 26 . These results are in contradiction with those observed by Finsterbusch et al 27 . These authors found a strong correlation between Ki67 in IHC and mRNA level of Ki67 obtained by Mammatyper in 101 patients.…”

<p>microRNA-582 Potentiates Liver and Lung Metastasis of Gastric Carcinoma Cells Through the FOXO3-Mediated PI3K/Akt/Snail Pathway</p>

“…The number of KI67 positive cells in tumor sections was detected using immunohistochemistry as previously reported. 17 Briefly, tumor tissue sections were deparaffinized, rehydrated, and then incubated at 95°C in citrate buffer for 20 min for antigen retrieval. At room temperature, nonspecific binding was blocked with 10% normal goat serum for 30 min.…”

“…GATA6-AS1 overexpression has been reported in a literature to significantly inhibit GC proliferation and EMT. [3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20] As a consequence, we used RT-qPCR to detect the expression of GATA6-AS1 in tumor tissues and paracancerous tissues in 45 GC patients, and found that GATA6-AS1 was significantly lower in GC tissues (Figure 6C). We subsequently verified the binding relationship between GATA6-AS1 and miR-582 by dual luciferase experiments.…”

Value of genomics- and radiomics-based machine learning models in the identification of breast cancer molecular subtypes: a systematic review and meta-analysis

“…Luminal A and B are two relatively mild molecular subtypes of BRCA with better prognoses, and both are sensitive to endocrine therapy. The level of Ki67-labeled standardized proliferation is the most significant feature to distinguish the two ( 9 ). HER2-positive BRCA is characterized by its high invasiveness and high recurrence, with increased incidence year by year.…”