Neu Expression Research Articles

Equivocal HER-2/NEU Expression of Breast Carcinoma by Immunohistochemistry: Comparing the Rate of FISH Amplification Between Two Laboratories

Equivocal HER-2/NEU Expression of Breast Carcinoma by Immunohistochemistry: Comparing the Rate of FISH Amplification Between Two Laboratories

Multiple osteolytic lesions of intraosseous adenoid cystic carcinoma in the mandible mimicking apical periodontitis

Adenoid cystic carcinoma (ACC) is a relatively rare epithelial tumour of the salivary glands in the maxillofacial region. About 40-60% of the patients develop distant metastases, which have been documented most commonly in the lung but also in brain, bone, liver, thyroid, spleen and pancreatic gland. A 55-year-old women with intraosseous ACC in the mandible mimicking apical periodontitis following curative resection and radiotherapy is presented. Three years later, multiple lung metastases were observed followed by chemotherapy. Five years after curative resection, the patient presented simultaneously with new expansive soft tissue in the pancreas and mammary gland as well as in the kidney found to be metastatic ACC. No case has been reported to date on the manifestation of distant metastases of intraosseous ACC in the breast and the kidney as described by these observations. Metastatic mammary gland ACC stained positive for epithelial growth factor receptor (EGFR) but was negative for HER-2/neu and Cyclooxygenase-2 (COX-2) expression.

Prognosis significance of HER2/neu overexpression and amplification in patients with curatively resected gastric cancer.

e14539 Background: HER-2/neu targeted therapy has been successfully used in advanced gastric cancer, but the role of HER-2/neu inprognosis of gastric cancer is not yet clear. To investigate the correlation between HER-2/neu expression and amplification and their associations with clinicopathologic outcomes and prognosis in patients with curatively resected gastric cancer. Methods: We constructed tissue microarray blocks containing >70% of gastric cancer tissue and matched adjacent normal gastric tissue for 229 patients. Expression of the HER-2/neu protein in these specimens was analyzed using immunohistochemical (IHC) staining. Amplification of HER-2/neu was also analyzed for the same samples using fluorescence in situ hybridization (FISH). Kaplan Myers curve and Cox proportional hazards model were used to assess the survival. Results: Of the 229 gastric cancer samples, 14.85% were positive for HER-2/neu protein expression that was closely correlated to the Lauren type, degree of differentiation, tumor size, lymph node metastasis and overall survival. Overall, 11.79% of the 229 gastric cancers were positive for amplification of HER-2/neu, which was also closely correlated to the Lauren type, degree of differentiation, tumor size and overall survival. Moreover, Cox proportional hazards model showed that positive expression of HER-2/neu, Lauren type, tumor size, vessel invasion, TNM stage were independent prognostic factor. Both IHC and FISH assays provide an important prognostic factor for gastric cancer with a concordance rate of 96.9%, but IHC was a stronger independent prognostic factor. Conclusions: Expression of the HER-2/neu protein, compared with its gene amplification, was an independent and more sensitive prognostic factor for curatively resected gastric cancer patients.

A multicenter prospective study of image-guided radiofrequency ablation for small breast carcinomas.

TPS1147 Background: As the management of breast carcinoma evolves toward less invasive treatments, the next step is the possibility of removing the primary tumor without surgery. The most promising noninvasive ablation technique is radiofrequency ablation (RFA), which can effectively kill tumor cells with a low complication rate. Our preliminary studies of RFA followed by standard surgical resection have indicated that this technique is effective for surgical ablation of small (≤ 2cm) breast tumors without extensive intraductal components (EIC). Methods: To determine if RFA is oncologically and cosmetically appropriate for the local treatment of primary breast carcinoma, this multi-center prospective study used RFA as the sole local treatment of breast tumors ≤ 1.5cm in size on ultrasound and MRI. Exclusion criteria include receiving of preoperative chemotherapy, or the presence of invasive lobular carcinoma or invasive ductal carcinoma with suspicious EIC. After confirmation that the standard baseline core biopsy for diagnosis and measurement of tumors markers (ER, PgR, HER-2/neu expression and the presence of the Ki-67 proliferative marker) have been obtained, consent will be obtained and the patient scheduled RFA. All patients received adjuvant radiation therapy. The use and choice of systemic therapy will be based on the information from the baseline core biopsy and imaging studies. The first primary endpoints of this study is successful tumor ablation, as evidenced by negative findings on vacuum-assisted or core biopsies and imaging studies after RFA. The second primary endpoints is the incidence of procedure related adverse events. Forty patients with small tumors that are clearly identifiable and measurable by ultrasound and MRI were enrolled. The response to ablation was evaluated with both vacuum-assisted or core biopsies and imaging studies every 3 months during the first year. The long-term outcomes were assessed using quality of life measurement scales and imaging studies every 6 months thereafter through year 5.

Docetaxel, carboplatin, trastuzumab, and bevacizumab (TCH+B) for early-stage HER2/neu(+) breast cancer and bone marrow micrometastases.

TPS655 Background: Bone marrow (BM) micrometastases confer a poor prognosis to early-stage breast cancer (BC) and HER-2/neu(+) BC is a high-risk phenotype. We have shown that BM-associated stromal cells support the survival of metastatic BC in microenvironmental niches and this activity is dependent on VEGF and CXCL-12. Therefore, the growth of nascent tumor cell clusters in BM might be impeded by disrupting stromal cells or their activating ligands, such as VEGF. There is also a positive association between HER-2/neu and VEGF expression in BC, thereby implicating VEGF in the aggressive phenotype of HER-2/neu overexpression. These observations support the use of combination therapies directed against both HER-2/neu and VEGF for the treatment of HER-2/neu(+) BC. We therefore hypothesize that an anti-VEGF agent (bevacizumab) given with docetaxel, carboplatin and trastuzumab (TCH) will eradicate the BM of HER-2/neu(+) BC micrometastases by disrupting stromal cell support within the micrometastatic BM niche. Methods: Subjects with AJCC Stage I-III HER2/neu(+) BC will undergo a single iliac-crest BM aspirate and biopsy. If the BM is positive for CK+ micrometastases, up to 17 patients will receive TCH+B therapy (docetaxel at 75 mg/m2 IV and carboplatin at AUC 6 IV given every 3 weeks for 6 cycles; trastuzumab at 4 mg/kg IV loading dose, then 2mg/kg IV every week; bevacizumab at 15 mg/kg IV every 3 weeks). Four weeks after the 6th cycle of therapy, a repeat BM aspiration and biopsy will be performed to score for response of BC micrometastases to therapy. Patients with a complete clinical response in BM will continue with trastuzumab every 3 weeks at 6 mg/kg to a total of 1 year. Patients with persistent micrometastases will receive both trastuzumab and bevacizumab every 3 weeks to a total of 1 year of therapy. These patients will then have a repeat BM aspirate and biopsy at the end of the 1 year to score for final response. The primary objective of this clinical trial is to determine clinical response against BC micrometastases in BM. The second objective is to investigate the specific contribution of VEGF and CXCL-12 signaling to BM support of micrometastatic BC cells.

Hormone replacement therapy and its effect on HER2 neu status in primary breast cancer.

e11057 Background: Controversy has developed over the use of hormone replacement therapy (HRT) and its association with the future risk of breast cancer. The biology of breast cancer diagnosed after the use of HRT is different than in non HRT users. One such pathologic feature that may be affected by the use of HRT is HER2 neu. While there is existing data illustrating the relationship between HRT and breast cancer, there is little data examining the relationship between HRT and HER2 neu. The purpose of this study is to investigate that relationship and determine whether or not the use of HRT has any effect on the HER2 neu status of primary breast cancers. Methods: A retrospective review of a prospective database identified 2,928 patients with primary breast cancer with a history of prior/current HRT use. Tumor specimens were evaluated for HER2 neu expression at the time of surgery using either IHC or FISH. Pearson’s χ² test along with evaluation of odds ratios were used to determine whether or not there was an association of HER2 neu expression with HRT use. Results: Table 1A illustrates the lack of a correlation between increasing HER2 expression and HRT. There was no significant change in odds of HRT use as HER2 expression increased. After confirming HER2 neu status using FISH, the odds of HER2 positivity among HRT users was OR= 1.05 times the odds of HER2 neu positivity among non-HRT users [C.I. 0.85, 1.29; p = 0.63] (Table 1B). Conclusions: Contrary to our expectation of an inverse relationship between HRT use and HER2 negative phenotype, we found no clear association between the two. Limitations of this study include the inability to discriminate from our data set between current and prior users, and between estrogen alone and combination estrogen/progesterone supplementation. Additionally, the definition of HER2 positivity by membranous staining has changed over the last decade, which may be contributory. We plan on determining the relationship between HER2 status and ER status as it relates to HRT use in future studies. [Table: see text] [Table: see text]

The correlations between the expression of FGFR4 protein and clinicopathological parameters as well as prognosis of gastric cancer patients

Fibroblast growth factor receptor 4 (FGFR4) was seldom investigated in gastric cancer (GC). The purpose of the study was to elucidate the expression of FGFR4 protein in GC and related clinical significance. Ninety-four paraffin-embedded tumor specimens were obtained from Cancer Hospital, Fudan University. The expression of FGFR4 as well as p53, p21, EGFR, neu, c-myc, and PCNA were detected by immunohistochemical method. Then, correlation analysis and survival analysis were performed. The expression rate of FGFR4 protein in GC tissues and normal stomach tissues was 93.6% and 30.8%, respectively (P = 0.000). The expression of FGFR4 was positively correlated with the expression of p21, neu and PCNA (P-value was 0.009, 0.012, and 0.018, respectively). Subgroup analysis showed that compared to low expression group, the prognosis of patients with III/IV stage and negative expression of p21 in high expression group of FGFR4 were worse (P = 0.048, 0.041, respectively). Multivariate analysis showed that TNM stage was the independent prognostic factor in high expression group (HR, 11.593; 95% CI, 3.532-18.058; P = 0.000). High expression of FGFR4 protein, accelerating the progression of advanced GC, might be associated with a poor prognosis in patients with advanced FC.

Abstract 328: The mitotic kinase Aurora-A promotes breast cancer metastases by inducing a CD24low/- basal-like stem cell phenotype

Abstract In this study we demonstrate that gain of HER-2/Neu expression in human breast cancer xenografts harboring constitutive active Raf-1 induces Aurora-A over-expression that ultimately drives the transition from a luminal to a highly invasive basal-like phenotype. Over-expression of Aurora-A was induced by phosphorylation and protein stabilization by HER-2/Neu rather than increased Aurora-A gene expression. Moreover, Aurora-A stabilization induced an increase of HER-2/Neu expression in breast cancer cells defining a novel positive feed-back loop between Aurora-A and HER-2/Neu oncogenic signaling pathways. Basal-like tumor cells over-expressing Aurora-A and HER-2/Neu underwent to loss of CD24 surface receptor, expressed epithelial to mesenchymal transition (EMT) markers and acquired stem cell-like properties such as mammospheres formation and self-renewal. Pharmacologic inhibition of HER-2/Neu signaling pathway with lapatinib in cancer cells over-expressing Aurora-A demonstrated that Aurora-A was downstream to HER-2/Neu in the development of EMT and stemness. To determine whether Aurora-A induced a cancer stem cell-like phenotype through development of chromosomal instability and tumor cell phenotypic heterogeneity, we performed a SKY analysis on the breast cancer cell lines employed in this study. Our results demonstrate that invasive breast cancer cells harboring a basal-like phenotype did not develop higher chromosomal instability compared to luminal non-invasive cancer cells, signifying that Aurora-A has a direct effect on the development of basal-like breast cancer cells with stemness properties. Importantly, pharmacologic inhibition of Aurora-A kinase activity with the small molecule MLN8237 restored CD24 expression and reversed EMT leading to the re-establishment of a luminal phenotype and suppression of distant metastases. Our findings implicate for the first time the mitotic kinase Aurora-A in the development and maintenance of CD24 negative basal-like tumor stem cells responsible for breast cancer recurrence and progression. These observations have also important implications for the development of molecular targeted therapies to inhibit Aurora-A kinase activity and stemness improving the overall survival of breast cancer patients. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 328. doi:1538-7445.AM2012-328

Abstract LB-325: Characterization of triple negative breast cancer patients among Hispanics in Puerto Rico

Abstract Introduction: Hormone receptor status had been correlated with prognosis in breast cancer patients. Breast cancer patients with no expression of estrogen receptor (ER), progesterone receptor (PR) and her-2 neu (her-2) have been grouped in the Triple Negative Breast Cancer (TNBC) category. At present, these patients have very limited adjuvant therapy alternatives. TNBC has been correlated with poor prognosis among African-American and Hispanic populations. However, there is very few data regarding the prevalence and characterization of TNBC among Hispanics groups (e.g. Puerto Ricans, Cubans, etc.). The objective of this study is to characterize the TNBC population among the Puerto Rican population and to assess whether expression of ER changes the characteristics of the disease in this group. We hypothesize that expression of ER+ in her-2 negative breast cancer tumors will change the initial presentation of the disease. Methods: This cross-sectional study analyzed data from female patients with breast cancer diagnosed between 2000 and 2005, at the I. Gonzalez Martinez Hospital and the Auxilio Mutuo Hospital (n=1,082) in San Juan, Puerto Rico. Information on Her-2 status and other clinical characteristics were retrieved from the hospital's cancer registries and from medical record review. This study was approved by the Institutional Review Boards of the participating hospitals. Logistic regression models were used to evaluate the associations between relevant clinical characteristics and TNBC. We also evaluated whether there were any interaction between age, tumor size and receptor status. Results: The prevalence of TNBC in our study was 16.3% and 58.7% for the Her-2-ER+s phenotype. Patients in the TNBC group have a younger age (<50 yr.) at diagnosis (24.3% vs 75.7%), larger tumor size (>2cm) (70.3% vs 45.6%), invasive ductal histology (87.3% vs 68.7%), and higher tumor grades (III-IV) (49.7% vs 13.2%) compared to Her-2-ERs+. Using multinomial models, we found that, compared to TNBC, women with Her-2-ER+PR- and those with Her-2-ER+PR+ were 1.99 (CI95%=1.15,3.44) and 1.66 (CI95%= 1.11, 2.46) times more likely to have > 50 years at diagnosis as compared to those with <50 years. This relationship is not seen in women with Her-2-ER-PR+ tumors. Furthermore, compared to TNBC, women with Her-2-ER+PR- are 0.4 (IC95%=0.24-0.67) times more likely to have tumors > 2cm. There was no interaction between receptor status, age and tumor size (p=0.582). Conclusions: TNBC in Hispanics from Puerto Rican origin showed the same prevalence of Hispanic women in California. Furthermore, disease characteristics (early age at diagnosis, tumor size, histology and tumor grade) were also similar, suggesting that race has a significant effect in the presentation of TNBC in Hispanic women. In addition, the expression of ER, but not PR in Her-2 negative patients dramatically changes the initial presentation of the disease. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr LB-325. doi:1538-7445.AM2012-LB-325

Variability in hormone and growth factor receptor expression in primary versus recurrent, metastatic, and post-neoadjuvant breast carcinoma

The introduction of selective molecular targeted therapy, specifically tamoxifen and trastuzumab, has significantly altered the clinical behavior of breast carcinoma. Several questions remain, however, regarding potential phenotypic drifts in estrogen receptor (ER), progesterone receptor (PR), and epidermal growth factor receptor (Her-2/neu) expression between the primary and metastatic site. Whether patients should be tested for ER, PR, and Her-2/neu expression in the nodal or distant metastatic site, local recurrence and following neoadjuvant therapy, and whether this has an effect on prognosis remains elusive. A review of 45 studies addressing ER, PR, and Her-2/neu expression in lymph node metastasis, distant metastasis, local recurrence, and post-neoadjuvant therapy revealed the following average phenotypic drift in ER, PR, and Her-2/neu expression, respectively: 13.1 % (median = 10.0 %), 13.8 % (median = 16.0 %), and 7.7 % (median = 5.0 %) for lymph node metastasis; 21.8 % (median = 19.5 %), 30.8 % (median = 33.5 %), and 7.6 % (median = 6.1 %) for distant metastasis; 19.8 % (median = 13.4 %), 27.1 % (median = 28.6 %), and 6.6 % (median = 1.6 %) for local recurrence; and 12.9 % (median = 8.0 %), 32.0 % (median = 20.0 %), and 8.9 % (median = 0 %) post-neoadjuvant therapy. The above findings support the notion of re-evaluating ER, PR, and Her-2/neu expression in distant metastasis, lymph node metastasis and to a lesser extent local recurrence. The effects of neoadjuvant therapy on receptor expression are more pronounced for PR, which may have a prognostic role in therapy efficacy.

HER2/neu expression in locally advanced rectal cancer cUICC II/III and its correlation with long-term prognosis.

493 Background: With the implementation of multimodal treatment strategies including neoadjuvant radiochemotherapy (RCT), the prognosis of locally advanced rectal cancer has been improved over the last two decades. Most actual clinical trials aim to further develop therapy by intensification of agents administered. We examined Her2/neu in rectal cancer patients to evaluate its expression as a potential drug target as well as its capacity as predictive and prognostic biomarker. Methods: Two-hundred-seventy-seven patients (205 male, 72 female; median age 63.5 years) with locally advanced rectal cancer (cUICC-II/III) were included in this study. Preoperative RCT (50.4 Gy and concomitant either 5-FU or 5-FU and oxaliplatin) was administered in 236 patients followed by surgical resection with total mesorectal excision (TME). Another 41 patients received postoperative RCT. All patients were treated within phase-II/-III-trials of the German Rectal Cancer Study Group or analogous to these standardized protocols. Her2-/neu expression from pre-treatment biopsies and corresponding resection specimens were assessed by immunohistochemical staining and SISH-analysis. Results: A positive Her-2/neu expression was found in 12.3% of all pre-treatment tumor biopsy samples and in 28.7% of the resection specimens. The correlation of the pre-treatment Her-2/neu status did not show a significant correlation with the grade of tumor regression. However, patients with a higher Her-2/neu protein expression as measured in the resection specimen showed a significant survival benefit (p=0.0277) compared with patients having low intratumoral Her-2/neu expression during the follow-up (median 43 months). The 10-year survival rate was 73.2% (Her-2/neu positive) versus 60.1% (Her-2/neu negative). Conclusions: The proportion of patients with a positive Her-2/neu status is relevant in rectal cancer. Her-2/neu might potentially serve as a promising drug target in rectal cancer and should be further assessed within prospective clinical trials. Furthermore the Her-2/neu status seems to be a valuable prognostic marker within the multimodal treatment of advanced rectal cancer.

HER‐2 pulsed dendritic cell vaccine can eliminate HER‐2 expression and impact ductal carcinoma in situ

HER-2/neu overexpression plays a critical role in breast cancer development, and its expression in ductal carcinoma in situ (DCIS) is associated with development of invasive breast cancer. A vaccine targeting HER-2/neu expression in DCIS may initiate immunity against invasive cancer. A HER-2/neu dendritic cell vaccine was administered to 27 patients with HER-2/neu-overexpressing DCIS. The HER-2/neu vaccine was administered before surgical resection, and pre- and postvaccination analysis was conducted to assess clinical results. At surgery, 5 of 27 (18.5%) vaccinated subjects had no evidence of remaining disease, whereas among 22 subjects with residual DCIS, HER-2/neu expression was eradicated in 11 (50%). When comparing estrogen receptor (ER)(neg) with ER(pos) DCIS lesions, vaccination was more effective in hormone-independent DCIS. After vaccination, no residual DCIS was found in 40% of ER(neg) subjects compared with 5.9% in ER(pos) subjects. Sustained HER-2/neu expression was found in 10% of ER(neg) subjects compared with 47.1% in ER(pos) subjects (P = .04). Postvaccination phenotypes were significantly different between ER(pos) and ER(neg) subjects (P = .01), with 7 of 16 (43.8%) initially presenting with ER(pos) HER-2/neu(pos) luminal B phenotype finishing with the ER(pos) HER-2/neu(neg) luminal A phenotype, and 3 of 6 (50%) with the ER(neg) HER-2/neu(pos) phenotype changing to the ER(neg) HER-2/neu(neg) phenotype. Results suggest that vaccination against HER-2/neu is safe and well tolerated and induces decline and/or eradication of HER-2/neu expression. These findings warrant further exploration of HER-2/neu vaccination in estrogen-independent breast cancer and highlight the need to target additional tumor-associated antigens and pathways.

HER-2/neu and TOPIIα Expression in Gastric Cancer Reflect Disease Severity

Gastric cancer is associated with high morbidity and mortality, but reliable diagnostic and prognostic markers have not been established. Here we explored the clinical significance of two proteins, HER-2/neu and TOPIIa-associated with development and progression of various tumor types-in gastric cancer. We also analyzed the correlation between expression of these proteins and clinicopathological parameters of gastric tumors. Tumor and adjacent normal tissue samples were collected from 62 patients with gastric cancer and subjected to immunohistochemistry with anti-HER-2/neu and -TOPIIa antibodies. HER-2/neu (21.0%) and TOPIIa (80.6%) were expressed more commonly in gastric cancer than in normal gastric tissue (9.7% and 60.3%, respectively; p<0.05). However, there was no correlation between HER-2/neu and TOPIIa expression in gastric tumors. Further analysis showed a correlation between HER-2/neu expression and lymph node metastasis, distant metastases and tumor stage (p<0.05); TOPIIa was correlated with infiltration depth, distant metastases and tumor stage (p<0.05). HER-2/neu and TOPIIa are over expressed in gastric tumors and may promote disease progression. These proteins may therefore be useful as prognostic markers in evaluation of patients with gastric cancer.

The Frequency of K-ras Mutation in Colorectal Adenocarcinomas with Absence of Distant Metastasis at Diagnosis

Purpose: K-ras mutations were reported to be in 40% - 60% of patients with sporadic colorectal cancers (CRCs). HER-2/neu oncogene that is important in breast carcinoma was reported in CRCs in several studies. The aims of our study are to determine; the frequency of K-ras mutation in CRC and positivity of HER-2/neu, the relation between K-ras mutation and HER-2/neu positivity, and also the relation between clinicopathological findings with K-ras mutation and HER-2/neu expression. Methods: Total of 35 colon resection specimen from patients without distant metastasis who were operated due to colorectal adenocarcinoma were included in the study. The sections were examined with light microscopy. Vascular and perineural invasions and pericolonic tumor deposits (PCTD) were investigated. HER-2/neu was applied immunohistochemically. DNA sample obtained from tumor paraffin block was screened for presence of 20 mutations in K-ras gene-codon 12, 13, 61 by AutoGenomics and Infinity Analyzer. Results: K-ras gene mutation was detected in 14 of 35 patients (40%). HER-2/neu positivity was detected in 7 cases (28.57%). There was not any significant correlation between HER-2/neu positivity, K-ras gene mutation and clinicopathological findings. There was direct correlation between PCTD and vascular invasion. Conclusions: There was not correlation between K-ras mutation and clinicopathological findings similar to several other studies. The relation between HER-2/neu expression and clinicopathological findings was not found.

Correlation of hormone receptors with her-2 neu protein expression and the histological grade in invasive breast cancers in a cohort of saudi arabia

Data on Hormone Receptor and Her-2/neu expression in breast cancers from Saudi Arabia and Gulf Region is sparse. We undertook this study to describe the patterns of hormone receptor and Her-2/neu protein expression in breast carcinoma and compared them with the histological grade at a University Hospital in Riyadh. We conducted a retrospective study on 164 invasive ductal carcinoma of breast between the year 2002 and 2008. Immunohistochemical analysis for Estrogen and Progesterone Receptor and Her-2/neu was done in all the cases. Fluorescent in situ hybridization for Her-2/neu gene amplification was performed in all 2+ cases and few equivocal 1+ and 3+cases by immunohistochemistry. Correlation between Estrogen and Progesterone Receptor and Her-2/ neu amplification and grade of tumor was calculated. The expression of Estrogen Receptor, Progesterone Receptor were significantly correlated (p < 0.001). Also, there was a significant negative correlation between expression of hormone receptor and Her-2/neu amplification. The histologic grade of the tumor was significantly correlated to the expression of both Estrogen and Progesterone Receptor. However, the relationship between Her-2/ neu amplification and grade was not significant and many of the grade III tumor were Her-2/neu negative. In addition, Her-2/neu gene amplification by fluorescent in situ hybridization was observed in 84.6% of breast cancer that were 3+ and in 18.75 % cases that were 2+ by immunohistochemistry. Prevalence of Estrogen and Progesterone Receptor expression and Her-2/neu amplification in breast cancer in the Saudi Arabian population is similar to that reported internationally. There is a negative correlation between hormone receptors expression and Her-2/neu amplification. However not all of the high-grade breast cancers showed Her-2/neu positive status.

HER-2/neu oncogene and estrogene receptor expression in non small cell lung cancer patients

Non-small cell lung cancers are among the leading causes of cancer morbidity and mortality worldwide. The prognosis is usually based on traditional pathohistological parameters and clinical stage, but additional prognostic survival factors have also been sought. The aim of this retrospective study was to explore the membranous expression of HER-2/neu and estrogen receptors in nonsmall cell lung cancers and their relation to survival of patients with non-small cell lung cancers and to traditional prognostic factors. The sample consisted of 132 consecutive, surgically resected patient tissues of non-small cell lung cancers, and the following parameters were examined: HER-2/neu and estrogen receptor expression, as well as the related clinical and pathological features: tumor, nodes, and metastases stage, level of tumor necrosis, histological and nuclear grade, lymphocytic infiltrate, and number of mitoses. HER-2/neu was positive in 28.8% of tumor samples, and estrogen receptor expression was positive in 29.5% of tumors, but neither was significantly associated with the outcome of non-small cell lung cancers. There was a significant association between HER-2/neu and nuclear grade (P=0.01). In addition, the association between estrogen receptor expression and histological type of tumor (P=0.04) and mitotic rate (P=0.008) was found. Kaplan-Meier analysis showed a significant association of patients' overall survival with the tumor node metastasis stage (P<0.001) and the degree of tumor necrosis (P=0.02). Cox proportional hazard regression analysis showed that male gender (P=0.01), histological type (P=0.03), high degree of necrosis (P=0.006), and higher histological grade (P=0.037) were associated with the patients' survival. Our findings indicate that the expression of HER-2/neu and estrogen receptor is less reliable than traditional histological parameters in predicting the survival of patients with non-small cell lung cancers.

OT2-05-06: ACOSOG Z11101/ACRIN 6694: Effect of Preoperative Breast MRI on Surgical Outcomes, Costs and Quality of Life of Women with Breast Cancer.

Abstract Background Surgical planning and local-regional treatment of breast cancer relies on accurate assessment of disease extent including the primary tumor size and the presence/absence of multiple tumor foci. As a staging modality for breast cancer, MRI has shown high sensitivity for detection of additional foci of diseases within the index breast. However, the impact of preoperative breast MRI on reducing re-excision rates and improving local control is less clear. Data from the COMICE trial in the UK suggested that routine use of pre-operative breast MRI did not alter rates of re-excision; however issues have been raised about the lack of quality standards for the MR imaging that may have resulted in the negative results of this trial. Retrospective data suggest that local recurrence is not impacted by use of breast MRI. In concert with data showing no improvement in clinical outcomes of breast cancer patients, concerns have been raised that routine use of preoperative breast MRI is associated with increased rates of mastectomy and delays to surgery. Therefore, the application of MRI for preoperative surgical staging remains controversial. In order to address this ongoing controversy, a joint effort has been launched by ACOSOG and ACRIN for a prospective clinical trial focused on evaluating the impact of preoperative breast MRI on clinically relevant patient outcomes. An important part of this collaboration is implementation of standards of how MRI findings should be clinically managed and used to direct localization methods and surgical planning, thereby creating guidelines for subsequent patient intervention. Trial design/eligibility criteria: A prospective multicenter trial will include women eligible for BCT by standard criteria and randomized between current standard of care, clinical examination and mammography (+/− ultrasound) and the same plus preoperative breast MRI. The study will focus on women at the highest risk of local recurrence: ER/PR/HER-2 negative (triple negative) and HER-2 amplified breast cancers. Specific aims: To compare the rates of local recurrence following breast conserving therapy in a cohort randomized to preoperative staging with mammography or mammography plus breast MRI. Additionally, a comparison of rates of re-operation, time to local recurrence, survival outcomes, contralateral breast cancer rates, rates of multicentric disease and other secondary aims will be performed. Costs and quality of life measures will also be investigated. Statistical methods: A stratified logrank test and Cox partial likelihood score test will be used to assess whether the distribution of LR times differs with respect to diagnostic work-up approach having adjusted for tumor stage. Cox modeling with the Cox partial likelihood score test will be used to examine the strength of association between these time to event distributions and such additional potential prognostic factors as menopausal status, chemotherapy, radiation therapy, ER, PR, number of positive lymph nodes, HER-2/neu expression, Nottingham grade, and Ki-67 expression. Target Accrual: 556 patients Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr OT2-05-06.

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.

Absence of caveolin-1 alters heat shock protein expression in spontaneous mammary tumors driven by Her-2/neu expression

In a previous study, we measured caveolin-1 protein levels, both in the normal breast and in breast cancer. The study revealed no association between caveolin-1 expression in the epithelial compartment and clinical disease outcome. However, high levels of caveolin-1 in the stromal tissue surrounding the tumor associated strongly with reduced metastasis and improved survival. Using an animal model, we found that the onset of mammary tumors driven by Her-2/neu expression was accelerated in mice lacking caveolin-1. We have analysed the heat shock protein (Hsp) response in the tumors of mice lacking caveolin-1. In all cases, the mammary tumors were estrogen and progesterone receptor negative, and the levels of Her-2/neu (evaluated by immunohistochemistry) were not different between the caveolin-1 +/+ (n=8) and the caveolin-1 -/- (n=7) tumors. However, a significant reduction in the extent of apoptosis was observed in mammary tumors from animals lacking caveolin-1. While Bcl-2, Bax, and survivin levels in the tumors were not different, the amount of HSPA (Hsp70) was almost double in the caveolin-1 -/- tumors. In contrast, HSPB1 (Hsp27/Hsp25) levels were significantly lower in the caveolin-1 -/- tumors. The mammary tumors from caveolin-1 null mice expressed more HSPC4 (gp96 or grp94), but HSPC1 (Hsp90), HSPA5 (grp78), HSPD1 (Hsp60), and CHOP were not altered. No significant changes in these proteins were found in the stroma surrounding these tumors. These results demonstrate that the disruption of the Cav-1 gene can cause alterations of specific Hsps as well as tumor development.

HER-2/neu Assessment for Gastric Carcinoma: Validation of Scoring System

Gastric cancer is the second leading cause of cancer mortality in the world. Amplification of HER-2/neu oncogene has become an important biomarker for identifying patients who respond to HER-2 targeting therapy. A number of studies have analyzed HER-2/neu overexpression in gastric carcinoma, and the rate of HER2 positivity is variable, ranging from 6% to 35%. In our study HER-2/neu expression was assessed on 73 samples of primary gastric cancer, using immunohistochemistry. For 19 patients preoperative biopsy samples and resected specimens were available. Additionally, internal ring study was performed to estimate intraobserver variability of IHC scoring among pathologists at our department. HER-2/neu overexpression was found in 10 (13.6%) of the tested samples, and it was more common in intestinal (22.5%) than the diffuse type (3.7%). Not one of the 6 analyzed mixed type tumors showed HER-2/neu expression. For the paired samples (preoperative biopsy samples and resected specimens) the concordance rate for HER-2/neu expression was 94.7%. According to high concordance rate in paired samples we consider it appropriate to evaluate HER2 expression on biopsy specimens, especially in unresectable cases, and to re-evaluate it on resected specimens if available, due to high heterogeneity of a gastric cancer.