In the current study, the expression of claudin-1, -3 and -4, E- and N-cadherin and the standard BC biomarkers [oestrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2) and marker of proliferation Ki-67 (Ki-67)] in formalin-fixed, paraffin-embedded sections from 62 patients with invasive BC was analysed using immunohistochemistry prior to and following neoadjuvant chemotherapy.
Use of an automated diagnostic platform (GeneXpert®) and assay (Xpert® Breast Cancer STRAT4) that employs RT-qPCR to quantitate ESR1, PGR, ERBB2, and MKi67 mRNAs from formalin-fixed, paraffin-embedded (FFPE) tissues facilitates analyses in less than 3 h. This study compares breast cancer biomarker analyses using an RT-qPCR-based platform with analyses using standard IHC and FISH for assessment of the same biomarkers.
We used this system with a research use only version of the Breast Cancer STRAT4 cartridge that measures the mRNA expression levels of ERBB2, ESR1, PGR, and MKi67.
Purpose To determine the pathologic complete response (pCR) rate in estrogen receptor (ER) -positive primary breast cancer triaged to chemotherapy when the protein encoded by the MKI67 gene (Ki67) level was > 10% after 2 to 4 weeks of neoadjuvant aromatase inhibitor (AI) therapy.
Ten international pathology institutions participated in this study and determined messenger RNA expression levels of ERBB2, ESR1, PGR, and MKI67 in both centrally and locally extracted RNA from formalin-fixed, paraffin-embedded breast cancer specimens with the MammaTyper® test.
Breast cancer subtypes approximated with RT-qPCR and IHC show good concordance, but cancer MKI67 mRNA content correlated slightly better with DDFS than Ki-67 expression.
In addition, 296 human breast cancer specimens were classified according to the presence of the fibrous or adipose stroma and analyzed by immunohistochemistry for the expression of estrogen and progesterone receptors, human epidermal growth factor receptor 2, antigen Ki-67, N-cadherin, Twist-related protein 1 (TWIST1), high-mobility group AT-hook 2, TGFβ, and S100 calcium-binding protein A4 using tissue microarray.
Nuclear pleomorphism and immunohistochemical reactivity for p53 protein and MIB-1 were evaluated on formalin-fixed paraffin-stored sections from 250 patients with breast cancer for whom the median follow-up duration was 6.4 years.
Proliferation of breast carcinoma cells was assessed by MIB-1 immunohistochemistry in sections of primary breast carcinomas and in residual tumour found in re-excision specimens, and in in-vitro cell lines by colorimetric assay.
Neoplastic lesions from the deleterious mutation carriers in the unilateral cohort had higher MIB-1 proliferation indices compared with other patients with and without a family history of breast carcinoma.
Down-regulation of beta(1C) expression in breast carcinomas correlated significantly with the tumor grade, the proliferative fraction (as evaluated by Ki-67 immunostaining with the MIB-1 monoclonal antibody), the estrogen and progesterone receptor status, and the tumor size (pT classification) and marginally with the node status.
In node-negative patients, only p53 exon 5 and 6 mutations and MIB-1 count were associated with a statistically significant increase in risk of death from breast cancer, independent of tumour size and ER concentration.
Evaluation of the findings for all 462 tumors as well as for node-positive and -negative subgroups revealed less favorable findings for overall survival and the disease-free period for both p53-positive tumors (for total group, overall survival, P = 0.0002, disease-free period, P = 0.02; for node-positive group, overall survival, P = 0.0004, disease-free period, P = 0.1045) and breast carcinomas with higher proportions of cell nuclei positive for MIB-1 (total, overall survival, P = 0.0026, disease-free period, P = 0.0022; node-positive, overall survival, P = 0.021, disease-free period, P = 0.0882).