Oncogenic mutations in Her-2/neu or k-ras had no association with the severity of endometrial cancer, but the presence of chromosomal aberrations, as a whole or dup(1q) alone, were associated with higher tumor size, deeper myometrial invasion, advanced stage or grade, lymphovascular invasion, and lymph node involvement (p < 0.05 for all).
The nuclear shift of maspin was more frequent in HER-2/p53-positive intestinal type adenocarcinomas with diffuse architecture at the invasion front, as well as for node-positive poorly cohesive carcinomas.
Although proliferation is the strongest parameter predicting clinical outcome in the ER+/HER2- subtype and the common denominator of most prognostic gene signatures, immune response and tumor invasion seem to be the main molecular processes associated with prognosis in the ER-/HER2- and HER2+ subgroups, respectively.
The analysis of concomitant P14ARF and TP73 overexpression and clinicopathologic parameters of the tumors showed a statistically significant difference with respect to peritumoral vessel invasion (P = 0.01), lymph node metastasis (P = 0.03), negative ERBB2 expression (P = 0.005), and more advanced pathologic stages (P = 0.03).
The logistic regression analysis for tumor invasion, lymph node metastasis and distant metastasis revealed that lymph node metastasis was most closely associated with the HER-2 genotype.
Univariate analyses showed that histological Grade 2, Grade 3, and HER2-positive status were associated with DCIS with invasion, odds ratios 5.1 (P = 0.017), 5.2 (P = 0.01) and 3.34 (P = 0.001), respectively.
Although a negative crosstalk between these two molecules was shown, double knockdown of both FOXO1 and HER2 in GC cells revealed that HER2 silencing reversed the FOXO1 shRNA-induced migration and invasion even without the FOXO1 restoration.
Gelatin zymography showed that flavopiridol inhibits the secretion of matrix metalloproteinase (MMP; MMPs 2 and 9) in the breast cancer cells and that the inhibition of c-erbB-2 and MMPs may be responsible for the inhibition of cell invasion observed in flavopiridol-treated cells.
We have also shown, by use of exogenously expressed PTEN and by treatment with the PI3'-kinase inhibitor LY294002, that ERBB-2-induced invasion is dependent on the PI3'-kinase pathway; however, PTEN does not dephosphorylate FAK in these cells.
We evaluated 173 consecutive breast carcinomas for c-erbB-2 using a combination of immunohistochemistry (IHC) with a commercial polyclonal antibody (Nitirei) and dual-color fluorescence in situ hybridization (FISH) using the c-erbB-2-specific probe and the chromosome 17 centromere-specific probe from Vysis (Downers Grove, IL) and compared the results with the histologic characteristics of intraductal spread, cancer invasion, and intratumoral heterogeneity.
We compared the clinicopathologic features of the two groups including nuclear grade, histologic grade, hormonal receptor status, human epidermal growth factor receptor-2 (HER-2) status, lymphovascular invasion, negative margin width, use of adjuvant therapy, and parenchymal SER around the tumor on preoperative DCE-MRI.
Finally, χ² statistical analysis was performed to analyze the HER2 positivity rate amongst the subgroups with different clinicopathological characteristics including; gender, age, tumor location, Lauren classification, differentiation, TNM staging, depth of invasion, lymph node metastases and distant metastasis.
We characterized myeloid zinc finger 1 (MZF1) as a CHIP target, given its recently identified role as a positive regulator of cathepsin B/L (CTSB/L)-mediated tumor cell invasion downstream of ErbB2.
Coexpression of epidermal growth factor receptor (EGFR) and the HER-2 oncoprotein has been reported to be related to the invasion and an adverse clinical outcome of human pancreatic ductal adenocarcinomas.
It is noteworthy that coexpression of Grb7 with epidermal growth factor receptor or Her2/erbB2 was detected in 10 esophageal carcinomas (31.3%) and was significantly related to extramucosal tumor invasion (P = 0.02), whereas such a relationship was not shown by each sole expression.
These findings reveal for the first time that: a) Enhanced synthesis and secretion of members of the IL-8/GRO chemokine family, which have recently been linked to oestrogen receptor (ER) inaction, increased cell invasion and angiogenesis, may represent a new pathway involved in the metastatic progression and endocrine resistance of HER2-overexpressing breast carcinomas, and b) Circulating levels of IL-8 and GRO cytokines may represent novel biomarkers monitoring breast cancer responses to endocrine treatments and/or HER2-targeted therapies.
For many years, patient age, axillary lymph node status, tumor size, histological features (especially histological grade and lymphovascular invasion), hormone receptor status, and HER2 status have been the major factors used to categorize patients with breast cancer in order to assess prognosis and determine the appropriate therapy.