Neu Protein Overexpression Research Articles

Pattern of HER2 overexpression in urinary bladder carcinomas in Kano, Nigeria

Background: The worldwide distribution of bladder cancer varies, conforming to differences in environmental and genetic risk factors. HER2 neu is overexpressed in many human cancers, including urinary bladder carcinomas. The aim of this study is therefore to evaluate the pattern of HER2 positivity, and correlate HER2 positivity of urinary bladder carcinomas with age, gender of patients, histological subtypes, and tumor grades. Methods: This is a 2-year retrospective study from January 2015 to December 2016. Patients’ clinicopathological information was extracted from their case folders and pathology reports. The histological subtyping using the WHO 2016 classification and grading was done and then reviewed by authors. HER2 scoring was done using the recommendations of the American Society of Clinical Oncology/College of American Pathologists. Results: Sixty cases of bladder cancer were diagnosed during the study period. HER2/neu positivity (3+) was observed in 24 (40%) of all the cases. Statistically significant association was observed between HER2 neu protein overexpression and increasing tumor grade (p≤ 0.001). Conclusion: This study recorded HER2 overexpression in 40% of study subjects. There is a statistically significant association between HER2 overexpression and increasing tumor grade.

Trastuzumab + FOLFOX6/FLOT as perioperative therapy for HER2-positive resectable gastric cancer and cardioesophageal transition: RussTrastPraсtik study (interim analysis)

Objective. The aim of this study was to evaluate the efficacy and safety of trastuzumab in combination with the FLOT/FOLFOX regimen in the perioperative treatment of resectable HER2-positive locally advanced gastric cancer. Methods. 15 patients were included in two groups; 4 patients were treated with trastuzumab (Herticad®, BIOCAD) + FLOT and 11 patients were treated with trastuzumab (Herticad®, BIOCAD) in combination with FOLFOX. The primary endpoint was incidence of disease stage reduction, tumor regression rate (TRG), change in HER2 tumor status, disease-free and overall survival. Results. Тrastuzumab in combination with FLOT/FOLFOX has a good therapeutic effect and a safety profile in the perioperative treatment of patients with resectable HER2-positive advanced gastric cancer (complete tumor regression [TRG1] was morphologically confirmed in 20% of patients, no pathomorphosis or minimal manifestations [TRG3/TRG4] in 40% of patients, in 40% of patients it was possible to achieve significant pathomorphological tumor regression [TRG2]). In addition, trastuzumab + FLOT gives better results in terms of tumor regression rate than FOLFOX + trastuzumab (cN+/ypN0 disease stage reduction in the T + FLOT group was 100%, whereas in the T + FOLFOX group it was only 30.0%). The HER2 status of the tumor changes against the background of preoperative PCT with the inclusion of trastuzumab (a loss of HER2/ neu protein overexpression was detected in 60% of patients).

Inter-observer agreement in reporting HER 2 Neu protein over expression by immunohistochemistry.

HER 2 Neu protein overexpression and its detection by immunohistochemistry (IHC) has become quiet critical because of its relevance in regards to Herceptin treatment. This peer review was done at a tertiary care center, which aimed at determining the inter-observer variation among five pathologists and evaluating the degree of agreement between them. The aim of our study was to determine the reproducibility of HER 2 Neu system of reporting in breast cancer cases and determine inter-observer variability among five pathologists at a tertiary care center. To compare the results with similar studies done at other centers. Retrospective descriptive study. Hematoxylin and Eosin (H and E) and IHC stained slides of 104 cases of carcinoma breast, on which HER 2 Neu status had been reported were reviewed. The time period for selection was from January 2010 to December 2011 (2 year period). Five pathologists reviewed the H and E and IHC slides independently and scored the results on a specially designed work sheet. Kappa values for inter-observer variation and Cornbach's alpha for internal consistency were calculated. SPSS 20.0 (IBM). not known. Complete agreement was seen between all five pathologists in 70 cases (70/104) = 67%. Agreement between four pathologists was seen in 78 cases (78/104) = 75%. Agreement between three pathologists was seen in 92 cases (92/104) = 88%. The global value for kappa co efficient for agreement between two pathologists was 0.706 and Cornbach alpha for internal consistency of reporting in the department was 0.987. CONCLUSION/KEY MESSAGES: Our departmental peer review indicated that there is good inter-observer concordance (agreement between two pathologists) and there is strong overall internal consistency of reporting for HER 2 Neu reporting by IHC. Our results are comparable to International reported data of similar studies.

Study of Her-2/neu and TOP2A expression in familial versus sporadic breast carcinoma

Introduction Genetic predisposition is one of the important risk factors that increase the incidence of breast cancer. The Her-2/neu gene is considered the most frequently amplified oncogene and is accompanied with either amplification or deletion of the TOP2A gene with an equal frequency. Aim of the study The aim of the study was to compare patients with familial breast cancer (FBC) with those having sporadic breast cancer (SBC) and also to evaluate the combined study on the hormonal status, immunostaining for Her-2/neu, and Her-2/neu and TOP2A copy number alterations by fluorescence in-situ hybridization (FISH). Patients and methods A total of 22 patients with invasive breast carcinomas were involved: 12 positive for the criteria that define FBC and 10 positive for SBC. Representative sections of formalin-fixed paraffin-embedded blocks were subjected to immunostaining for Her-2/neu (Hercep test), estrogen receptors, and progesterone receptors and also to FISH in order to evaluate TOP2A and Her-2/neu copy number alterations. Results FBC tumors were more aggressive than SBC tumors, as assessed by pathological parameters and immunohistochemical markers (lower estrogen receptor and progesterone receptor expression). However, the frequency of Her-2/neu gene amplification and protein overexpression was equal between the two groups. TOP2A gene amplification was observed in 25% of FBC patients compared with 20% of SBC patients. Coamplification of both Her-2/neu and TOP2A genes was observed in 8.3% of FBC patients and in 20% of SBC patients. In contrast, Her-2/neu amplification alone was observed in 25% of FBC patients compared with 10% of SBC patients. Importantly, TOP2A amplification without Her-2/neu gene amplification was observed in 16.7% of FBC patients but was not observed among SBC patients. Conclusion FBC tumors were more aggressive than SBC tumors. This study suggests that TOP2A gene amplification occurs both in FBC and in SBC patients but more frequently among FBC patients. Moreover, TOP2A gene amplification may occur independent of Her-2/neu amplification. We can conclude that this parameter should be determined on a routine basis in breast cancer patients, especially when FBC is suspected. In addition, a combined approach using immunohistochemical analysis and FISH can optimize Her-2/neu testing for breast carcinoma patients, especially among those with immunohistochemistry-equivocal tumors.

Quantification of Her-2/Neu Gene in Breast Cancer Patients using Real Time-Polymerase Chain Reaction (Q-PCR) and Correlation with Immunohistochemistry Findings

HER-2/neu is a proto-oncogene that encodes a transmembrane tyrosine kinase growth factor which is crucial for stimulating growth and cellular motility. Overexpression of HER-2/neu is observed in 10-35% of human breast cancers and is associated with pathogenesis, prognosis as well as response to therapy. Given the imperative role of HER-2/neu overexpression in breast cancer, it is important to determine the magnitude of amplification which may facilitate a better prognosis as well as personalized therapy in affected patients. In this study, we determined HER-2/neu protein expression by immunohistochemistry (IHC) concurrently with HER-2/neu DNA amplification by quantitative real time-polymerase chain reaction (Q-PCR). A total of 53 paired tissue samples from breast cancer patients were frozen-sectioned to characterize the tumour and normal tissues. Only tissues with 80% tumour cells were used in this study. For confirmation, Q-PCR was used to determine the HER-2/neu DNA amplification. We found 20/53 (37.7%) of the tumour tissues to be positive for HER-2/neu protein overexpression using IHC. Out of these twenty, only 9/53 (17%) cases were in agreement with the Q-PCR results. The concordance rate between IHC and Q-PCR was 79.3%. Approximately 20.7% of positive IHC cases showed no HER-2/neu gene amplification using Q-PCR. In conclusion, IHC can be used as an initial screening method for detection of the HER-2/neu protein overexpression. Techniques such as Q-PCR should be employed to verify the IHC results for uncertain cases as well as determination of HER-2/neu gene amplification.

The Effect Of HER-2/Neu Protein Overexpression on the Prognosis of Patients With Invasive Bladder Cancer Who Were Treated With Definitive Radiation Therapy

The Effect Of HER-2/Neu Protein Overexpression on the Prognosis of Patients With Invasive Bladder Cancer Who Were Treated With Definitive Radiation Therapy

Malignant transformation of adenomyoepithelioma of the breast by a monophasic population: a report of two cases and review of literature

Two cases of adenomyoepithelioma of the breast with malignant transformation by monophasic population of cells are presented. The underlying benign adenomyoepithelioma with typical biphasic architectural pattern was identified and represented at least 30% of the tumor in each case. In both cases, malignant portion of tumor was composed of relatively uniform monophasic population of highly atypical cells. The malignant component in case 1 was positive for pan cytokeratin, myoepithelial markers, and basal-type cytokeratins and also focally positive for luminal-type of cytokeratins, but negative for hormone receptors (estrogen and progesterone) and HER-2/neu protein overexpression. The malignant component in case 2 was positive for spectrum of myoepithelial markers but negative for luminal cytokeratins, hormone receptors and HER-2/neu protein overexpression. The bilinear immunophenotype in the case 1 suggests that the malignant tumor may have developed from precursor multipotent cells that can differentiate into both luminal epithelial and myoepithelial cells, although malignant component in case 2 appears to be the of pure myoepithelial phenotype.

Human epidermal growth factor receptor (HER 2)/neu expression and gene amplification in colorectal cancer

To investigate the relationship between the expression/amplification of human epidermal growth factor receptor (HER 2)/neu and its clinical significance in colorectal cancer, in this study, clinicopathological data and paraffin-embedded specimen were collected on 192 consecutive patients who underwent colorectal resections from 2001 to 2005 at Renmin Hospital of Wuhan University. Using immunohistochemistry and fluorescence in situ hybridization, HER-2/neu protein overexpression and gene amplification were detected. HER 2/neu was overexpressed in 32.3% of cases (62/192), of which 38 (19.8%) were 2 + and 24 (12.5%) were 3 + , over expression/amplification of HER 2/neu was associated with the differentiation and stage of the carcinoma. No association between the expression/amplification of HER 2/neu and the tumor size, location, age, gender and lymphatic invasion was found. HER 2/neu overexpression was significantly associated with HER 2/neu gene amplification according to univariate analysis; there was a significant difference in survival rates when cases with and without HER 2/neu overexpression or amplification were compared. These results indicate that HER 2/neu could be a prognostic variable in colorectal cancer; patients with colorectal cancer exhibiting high levels of HER 2/neu might benefit from the anti-HER-2 /neu therapy. Key words : HER 2/neu, colorectal cancer, immunohistochemistry, fluorescence in situ hybridization.

HER-2/neu Gene Amplification in Esophageal Adenocarcinoma and Its Influence on Survival

HER-2/neu (c-erbB-2, HER2) gene amplification and protein overexpression have been associated with poor prognosis in several solid tumors, including breast and gastric cancer. Its incidence and significance in esophageal adenocarcinoma is unknown. Tissue microarrays were successfully constructed from 89 paraffin-embedded archival specimens of esophageal adenocarcinomas for HER2 gene amplification by silver-enhanced in situ hybridization (SISH). No patients had undergone neoadjuvant therapy. Protein overexpression was tested with immunohistochemistry (IHC) using automated immunostaining (Ventana Benchmark). Incidence of HER2 positivity, correlation to clinicopathological variables in esophageal cancer patients, and concordance between SISH and IHC were determined. True HER2 gene amplification was detected in 14 esophageal cancer specimens (16%), and 92% of those with high-level HER2 amplification showed positive HER2 protein overexpression. No significant associations were found among gene amplification and clinicopathological factors. The 5-year survival rates were 57% for esophageal cancer patients with HER2 amplification compared with 32% without, but the difference in overall survival was not significant (P=.37). The correlation between SISH and IHC was statistically significant (P<.0001). While molecular targeting may be possible for approximately 16% of esophageal adenocarcinoma patients, HER2 oncogene amplification did not influence survival in this study.

Clinicopathological Characteristics and Her-2/neu Status in Chinese Patients with Uterine Papillary Serous Carcinoma

Objective. To analyze clinico-pathological features of Chinese patients with UPSC, and investigate roles of Her-2/neu protein expression and gene amplification in UPSC prognosis. Methods. Thirty-six patients with UPSC treated in Cancer Hospital of Fudan University from 1996 to 2006 were analysed retrospectively. Chromogenic in situ hybridization (CISH) and immunohistochemistry (IHC) were performed to evaluate Her-2/neu gene amplification and protein expression respectively. Results. The median age was 63 years, and 61% (22/36) were late stages (stage III/IV). The 1-year, 3-year, and 5-year overall survival (OS) was 73.1%, 51.9% and 43.9%, respectively. Advanced stages (P = .0006) and deep myometrial invasion (P = .0138) were significantly associtated with a shorter OS. In 36 cases, 27.8% (10/36) showed 2+ staining and 8.3% (3/36) showed 3+ by IHC. Amplification of the Her-2/neu gene was observed in 11.1% (4/36) cases. The 5-year overall survival rate in Her-2/neu IHC 2 + ∼3+ and 0 ~ 1+ cases was 12.9% and 68.6% respectively. Her-2/neu protein expression 2 + ∼3+ was significantly associated with advanced surgical stage and worse overall survival (P = .03 and P = .0023, resp.). Conclusion. Chinese patients with UPSC showed characteristics of deep myometrial invasion, advanced stages and poor overall survival. Her-2/neu protein overexpression is associated with advanced stage and poor survival outcome.

Is overexpression of HER-2 a predictor of prognosis in colorectal cancer?

BackgroundThe development of novel chemotherapeutic agents in colorectal cancer has improved survival. Following initial response to chemotherapeutic strategies many patients develop refractory disease. This poses a significant challenge common to many cancer subtypes. Newer agents such as Bevacizumab have successfully targeted the tyrosine kinase receptor epidermal growth factor receptor in metastatic colorectal cancer. Human epidermal growth factor receptor-2 is another member of the tyrosine kinase receptor family which has been successfully targeted in breast cancer. This may play a role in colorectal cancer. We conducted a clinicopathological study to determine if overexpression of human epidermal growth factor receptor-2 is a predictor of outcome in a cohort of patients with colorectal cancer.MethodsClinicopathological data and paraffin-embedded specimens were collected on 132 consecutive patients who underwent colorectal resections over a 24-month period at Mayo General Hospital. Twenty-six contained non-malignant disease. Her-2/neu protein overexpression was detected using immunohistochemistry (IHC). The HER-2 4B5 Ventana monoclonal antibody was used. Fluorescent insitu hybridisation (FISH) was performed using INFORM HER-2/Neu Plus. Results were correlated with established clinical and pathological predictors of outcome including TNM stage. Statistical analysis was performed using SPSS version 11.5.Results114 were HER-2/Neu negative using IHC, 7 showed barely perceptible positivity (1+), 9 showed moderate staining (2+) and 2 were strongly positive (3+). There was no correlation with gender, age, grade, Dukes' stage, TNM stage, time to recurrence and 5-year survival (p > 0.05). FISH was applied to all 2+ and 3+ cases as well as some negative cases selected at random. Three were amplified (2 were 3+ and 1 was 2+). Similarly, HER-2 gene overexpression did not correlate with established prognostic indicators.ConclusionHER-2 protein is over expressed in 11% of colorectal cancer patients. The gene encoding HER-2 is amplified in 3% of cases. Overexpression of HER-2 is not a predictor of outcome. However, patients who over express HER-2 may respond to Herceptin therapy.

No Strong Association Between HER-2/neu Protein Overexpression and Gene Amplification in High-grade Invasive Urothelial Carcinomas

The generation of urothelial carcinoma is caused by the accumulation of various molecular changes, as in most malignancies. There are conflicting data about the status of HER-2/neu oncogene in urothelial carcinomas. The aim of this study was to determine the status of HER-2/neu oncogene in high-grade invasive urothelial carcinoma of urinary bladder both in protein and DNA level. We evaluated HER-2/neu protein overexpression by immunohistochemistry (IHC) and gene amplification by fluorescent in situ hybridization (FISH) and real-time quantitative PCR in paraffin-embedded samples of high-grade invasive urothelial carcinoma obtained from 36 patients. Polysomy 17 was also assessed by FISH. Immunohistochemically, HER-2/neu protein overexpression was observed in 22 (61.1%) tumors (ten tumors with score 3+ and 12 with score 2+). Fourteen of 36 tumors (38.9%) were evaluated as negative (score 0 or 1+). Complete concordance between FISH and the PCR was seen in all of the samples scored as 0 and 1+ by IHC. HER-2/neu gene amplification was observed in three of 27 (11.1%) tumors by FISH (nine samples were non-informative) and in eight of 36 (22.2%) tumors by the PCR. The complete concordance between HER2-2/neu protein overexpression and gene amplification was seen only in three of 27 tumors. Polysomy 17 was seen in nine tumors (33.3%). The results indicated that, in contrast to breast cancer, there was no strong association between HER-2/neu overexpression and gene amplification in invasive urothelial carcinomas, and polysomy 17 was higher in tumors showing HER-2/neu overexpression.

Simultaneous analysis of HER-2/neu gene amplification and protein overexpression in single cells of pleural and ascitic effusions from patients with breast and ovarian cancer

Simultaneous analysis of HER-2/neu gene amplification and protein overexpression in single cells of pleural and ascitic effusions from patients with breast and ovarian cancer

Level of HER-2/neu protein expression in breast cancer may affect the development of endogenous HER-2/neu-specific immunity

We questioned whether the incidence or magnitude of the humoral or cellular immune response to the self-tumor antigen HER-2/neu is influenced by the level of HER-2/neu protein overexpression as defined by immunohistochemical staining of tumors in breast cancer patients. We obtained peripheral blood from 104 women with stage II, III, and IV pathologically confirmed HER-2/neu-overexpressing breast cancer. Patients were categorized with +1 (n = 14), +2 (n = 20), or +3 (n = 70) HER-2/neu overexpression by institutional pathologic report. Circulating antibodies to HER-2/neu were evaluated using ELISA. T-cell responses to HER-2/neu were measured using an antigen-specific tritiated thymidine incorporation assay. Eighty-two percent of subjects with HER-2/neu antibodies were +3 overexpressors compared with 18% +2 overexpressors and 0% +1 overexpressors, a highly significant difference (P < 0.001), and there were significant differences in the magnitude of the HER-2/neu-specific antibodies between groups with varying HER-2/neu protein expression (P = 0.022). In addition, 65% of subjects with HER-2/neu-specific T cells were +3 overexpressors compared with 16% +2 overexpressors and 19% +1 overexpressors (P = 0.001). Data presented here indicate that endogenous HER-2/neu-specific humoral and T-cell immunity is greater in patients with +3 protein overexpression in their tumors than in patients with lower levels of HER-2/neu expression. Overexpression of a self-tumor-associated protein is a potential mechanism by which immunogenicity is enhanced and may aid in the identification of biologically relevant proteins to target for immune-based molecular cancer therapies.

GRB-7 facilitates HER-2/Neu-mediated signal transduction and tumor formation

Growth factor receptor-bound protein-7 (GRB-7), an adaptor molecule, can interact with multiple signal transduction molecules. GRB-7 is amplified concurrently with HER-2/Neu in most, if not all, of breast cancer with chromosome 17q11-21 amplification. GRB-7 gene amplification is associated with RNA over-expression. We show GRB-7 protein is over-expressed by immunoblotting in breast cancer cell lines and primary breast tumors with HER-2/Neu protein over-expression. Over-expression of GRB-7 in MCF-7 breast cancer cells that over-express HER-2/Neu leads to activation of tyrosine phosphorylation of HER-2/Neu. Knockdown of GRB-7 expression in SKBR-3 breast cancer cells with naturally occurring HER-2/Neu gene amplification decreases tyrosine phosphorylation of HER-2/Neu. Activation of HER-2/Neu phosphorylation is associated with increase in tyrosine phosphorylation of phosphoinositide-specific lipase C-gamma-1 (PLC-gamma-1) and recruitment of PLC-gamma-1 to HER-2/Neu protein molecule. Activation of downstream protein kinase C (PKC) pathway is evidenced by increase in the phosphorylation of a common PKC substrate-myristoylated alanine-rich protein kinase C substrate (MARCKS). In addition, over-expression of GRB-7 in MCF-7 breast cancer cells that over-express HER-2/Neu leads to activation of AKT phosphorylation. Knockdown of GRB-7 expression in MB-453 and SKBR-3 breast cancer cells results in decrease in AKT phosphorylation. GRB-7 over-expression therefore facilitates activation of phosphorylation of HER-2/Neu and AKT in breast cancer cells with HER-2/Neu over-expression. GRB-7 over-expression in MCF-7 cells over-expressing HER-2/Neu leads to morphologic change of cells and promotes tumor xenograft growth in nude mice. GRB-7 over-expression therefore plays pivotal roles in activating signal transduction and promoting tumor growth in breast cancer cells with chromosome 17q11-21 amplification.

The Interactions Between GPR30 and the Major Biomarkers in Infiltrating Ductal Carcinoma of the Breast in an Asian Population

G-protein-coupled receptor 30 (GPR30) has been reported to be a novel estrogen receptor alpha (ERalpha) in vitro. Therefore, the interactions among GPR30, ERalpha, progesterone receptor (PR) and human epidermal growth factor receptor-2 (HER-2/neu), and their prognostic utilities in the infiltrating ductal carcinoma (IDC) of the breast were evaluated. Messenger RNA (mRNA) levels of GPR30, ERalpha, PR and HER-2/neu in the tumor samples of 118 Taiwanese IDC patients and 27 non-tumor mammary tissues were measured via quantitative polymerase chain reaction analyses. The correlations of GPR30 mRNA levels with clinical parameters, i.e. tumor/non-tumor, ERalpha, PR, HER-2/neu, age, lymph node metastasis, lymph-vascular invasion, grade, stage and patient survival, were assessed by using appropriate statistical analyses. GPR30 expression was observed to be lower in IDC (p < 0.001) than in non-tumor mammary tissues. Importantly, GPR30 mRNA level was positively correlated with that of ERalpha (p = 0.001) and PR (p = 0.001) but not correlated with that of HER-2/neu when they were analyzed as continuous variables. However, lower GPR30 was noticed in tumors with HER-2/neu protein overexpression. GPR30 expression was not correlated with age, lymph node metastasis, lymph-vascular invasion, grade and stage in IDC. GPR30 expression was not an independent prognostic factor for patient survival. GPR30 expression is downregulated in IDC. GPR30 is preferentially co-expressed with ER and/or PR but is lowly expressed in HER-2/neu(+) tumors. The correlation of GPR30 expression with clinical parameters, including patient survival, was not evident in this cohort.

Gene amplification and protein overexpression of HER-2/neu in human extrahepatic cholangiocarcinoma as detected by chromogenic in situ hybridization and immunohistochemistry: its prognostic implication in node-positive patients

In cholangiocarcinoma (CC), HER-2/neu protein overexpression has rarely been reported and the results are conflicting. The present study aimed to clarify the rates of HER-2/neu protein overexpression and gene amplification in human extrahepatic CC and to evaluate the correlation between HER-2/neu and several clinicopathologic features. We investigated HER-2 gene amplification by chromogenic in situ hybridization (CISH) and HER-2/neu protein overexpression by immunohistochemistry in 55 extrahepatic CC patients who underwent curative surgery at our institution. Overexpression of HER-2/neu protein (staining intensity score > or = 2) was found in 16 out of 55 patients (29.1%). CISH revealed that HER-2 gene signals were increased in 10 out of 55 patients (18.1%). There was a positive and significant correlation between HER-2 gene amplification and HER-2/neu protein overexpression (Spearman's rho = 0.718, P < 0.01). In subgroup with lymph node metastases, HER-2 gene amplification by CISH was significant prognostic factor for survival (OR 43.6, 95% confidence interval 1.6-1219.6). HER-2/neu protein overexpression by HER-2 gene amplification may occur in human extrahepatic CC and constitute an independent prognostic factor in patients with lymph node metastases. In subgroup with lymph node metastases who exhibit HER-2/neu overexpression might constitute potential candidates for new adjuvant therapy, such as humanized monoclonal antibodies.

HER-2/neu raises SHP-2, stops IFN-γ anti-proliferation in bladder cancer

Gene amplification or HER-2/neu protein overexpression signals a poor outcome for bladder cancer patients. We investigated the anti-proliferative effect of IFN-γ in HER-2/neu-transfected human bladder cancer cells (TCC-N5 and TCC-N10). The cells continued growing after IFN-γ stimulation but did not activate the Janus kinase (Jak)/Stat pathway. We found Jak/Stat protein phosphatase in TCC-N5 and TCC-N10 cells with upregulated Src homology 2-containing protein tyrosine phosphatase-2 (SHP-2). After the cells had been treated with AG825, a HER-2/neu-specific inhibitor, SHP-2 expression declined, and Jak2/Stat1 reactivated. Similar results were reported in a mouse bladder cancer cell line, MBT2, with constitutive HER-2/neu overexpression. Further, AG825 pretreatment restored the anti-proliferation activity of IFN-γ in TCC-N5 and TCC-N10 cells. Therefore, the suppression of IFN-γ signaling in HER-2/neu-overexpressing bladder cancer cells might be due to SHP-2 upregulation. The regulation of SHP-2 by HER-2/neu provides a new target for blocking the HER-2/neu oncogenic pathway.

Prognostic impact of HER‐2/neu expression on squamous head and neck carcinomas

HER-2/neu gene amplification and protein overexpression have been identified in various solid tumors, but its prognostic relevance in head and neck squamous cell carcinoma (HNSCC) is still controversial. The study investigated the expression of HER-2/neu oncoprotein in HNSCC and sought possible correlations to various clinicopathologic parameters. Expression of HER-2/neu oncoprotein was assessed in archival tumor tissues from 87 untreated HNSCC patients by immunohistochemical technique. Data were correlated with both the clinicopathologic parameters and patient survival. A high membranous HER-2/neu protein expression level was found in 39% of patients. Multivariate analysis indicated that HER-2/neu protein expression and pN lymph-node status were independent prognostic factors for disease-free survival. HER2/neu overexpression and its relationship with survival suggest that new therapeutic approaches targeting epidermal growth factor receptor (EGFR) family receptors could provide a new way of treating HNSCC patients with HER2/neu-positive neoplastic lesions.

Effect of HER‐2/neu overexpression on chemoresistance and prognosis in ovarian carcinoma

To investigate the effect of HER-2/neu protein overexpression on chemoresistance and prognosis in patients with epithelial ovarian carcinoma. A total of 141 ovarian carcinoma tissues surgically resected between 1987 and 2003 were assessed by immunohistochemistry (IHC). The characteristic of the patients and immunohistochemical results were compared by chi2-test. Survival analysis was performed by the Kaplan-Meier method and the log-rank test. HER-2/neu overexpression was detected in 18 cases (12.8%). There were no significant differences in histopathological subtypes (P = 0.3550), FIGO stages (P = 0.8858), or residual tumor size at first surgery (P = 0.6607) between the cases with HER-2/neu overexpression and the cases without HER-2/neu overexpression. Among the 58 cases which responded to chemotherapy, only five cases (8.6%) showed HER-2/neu overexpression. However, among the 38 cases which did not respond to chemotherapy, eight cases (21.1%) showed HER-2/neu overexpression. Overexpression of HER-2/neu had a tendency to relate with chemoresistance of epithelial ovarian carcinoma, but there were no statistically significant differences (P = 0.0817). No association was observed between HER-2/neu overexpression and cumulative survival rate (P = 0.4970). The results of the current study show that although HER-2/neu overexpression has a tendency to be associated with chemoresistance, it can not be a prognostic factor for the patients with epithelial ovarian carcinoma.