Intriguingly, HER2 inhibitors significantly reversed CUL4B-induced EMT in vitro and partially blocked GC metastasis in tumor xenografts with CUL4B overexpression.
Tissue microarrays have been used to determine the frequencies of amplication of 3 major breast cancer genes and identify overexpression of ERBB2 mRNA; assess and compare gene amplification in benign prostatic hyperplasia, primary prostate carcinoma, recurrent prostate tumors, and metastatic tumors; compare aggressiveness of prostate carcinoma in 2 patient populations; and study gene amplification across various tumor types.
Ado-trastuzumab emtansine (T-DM1/Kadcyla<sup>®</sup>;Genentech) is an antibody-drug conjugate used in the treatment of human epidermal growth factor receptor-2-positive metastasized breast cancer.
Genetic alterations of the proto-oncogene human epidermal growth factor receptor (HER-2/neu) have been shown to induce malignant transformation and metastasis.
Here, we investigated whether rVP1 exhibits any inhibitory effects on migration/metastasis and human epidermal growth factor receptor 2 (HER-2), a well-known biomarker for poor prognosis of breast cancer.
The incidence of C-erbB-2 positivity in lymph nodes with metastasis was higher than in primary sites (P < 0.01) and was significantly higher in differentiated adenocarcinoma (P < 0.01).
The aim of this study was to evaluate change in expression of hormone receptors and HER-2 status between primary tumour and corresponding local recurrence or distant metastasis.
Conclusions The significant discordance between HER-2/neu expression in primary and metastatic tumors suggests that determination of HER-2/neu status in metastatic disease should be attempted.
Interphase fluorescence in situ hybridization (FISH) demonstrated chromosomal amplification of the Her-2/neu locus within the tumor and a nodal metastasis.
The level of HER2/neu amplification tends to increase from the primary tumour to the paired metastases in a significant proportion of patients with HER2-positive MBC.
EGFR and HER2 positivity are more frequently found in favorable histological risk group of tumours (P = 0.004 and P = 0.01 respectively) while high expression of HER4 is significantly more often found in patients with metastatic disease (P = 0.03).
The association was also evident when comparing the distribution of the AA-GA genotype in patients in the following categories: 1) premenopause and obesity I (OR = 3.5, 95%CI = 1.3-9.3, P = 0.008), 2) Her-2 neu and tumor stage I-II (OR = 2.5, 95%CI = 1.31-4.8, P = 0.004), 3) premenopause and tumor stage III-IV (OR = 1.7, 95%CI = 1.0-2.9, P = 0.034), 4) chemotherapy non-response and abnormal hematocrit (OR = 2.4, 95%CI = 1.2-4.8, P = 0.015), 5) body mass index and Her-2 neu and III-IV tumor stage (OR = 2.8, 95%CI = 1.2- 6.6, P = 0.016), and 6) nodule metastasis and K-I67 (OR = 4.0, 95%CI = 1.01-15.7, P = 0.038).
Similarly, intrinsic subtyping of the metastases provided statistically significant post-relapse survival information with the worst survival outcome in the basal-like [hazard ratio (HR) 3.7; 95% confidence interval (CI) 1.3-10.9] and HER2-enriched (HR 4.4; 95% CI 1.5-12.8) subtypes compared with the luminal A subtype.
The status of HER2 expression in a cohort of samples obtained from 35 gastric cancer patients with peritoneal metastasis was investigated using immunohistochemistry and fluorescence in situ hybridization.
Over a 4-year period the HER2 positivity rate decreased for primary cancers from 23.8 to 14.6 %, but remained relatively constant for samples from metastases.
We compared these methods with 2 quantitative approaches, one measuring HER-2 gene copy number in tissue by real-time quantitative PCR (qPCR), and the other measuring shed HER-2 protein in serum by ELISA in patients with metastatic disease.
Patients with HER2 amplification showed shorter median times from disease discovery to LN metastasis (HER2 amplification vs HER2 non-amplification; 15.6 vs. 10.0 months; P=0.50) and from LN dissection to disease progression (HER2 amplification vs. HER2 non-amplification, 16.2 vs. 13.6 months; P=0.11).
A bone marrow aspirate sampled at the site of progressing metastasis in the right iliac bone was performed, and single cell molecular analysis using array-CGH of Epithelial Specific Antigen (ESA)-positive metastatic cells, and revealed two distinct regions of amplification, 12p12.1 and 17q12-q21.2 amplicons, containing the KRAS (12p) and ERBB2 (HER2/NEU) (17q) oncogenes.
Therefore, the c-erbB2/neu gene is proposed to be a metastasis-promoting gene, and its effects are at least partially mediated by the increased expression of alpha1,3-fucosyltransferase VII and SLe(x).
The BCT score outperforms prognostic models based on traditional clinicopathological factors and predicts the risk of distant metastasis in patients with HR+/HER2- early breast cancer.