Effect of human epidermal growth factor receptor 2 overexpression in metastatic colorectal cancer on standard chemotherapy outcomes.

Background: In metastatic colorectal cancer (mCRC), the prognostic relevance of the human epidermal growth factor receptor-2 (HER2) remains controversial. We evaluated the impact of HER2 overexpression on outcomes of standard chemotherapy in patients with mCRC. Methods: This retrospective study included patients with mCRC who received standard chemotherapy for mCRC and were tested for HER2 expression at Samsung Medical Center, Seoul, Korea, between January 15, 2017, and February 05, 2022. The HER2 test was performed using immunohistochemistry. We assessed the objective response rate (ORR), overall survival (OS), and progression-free survival (PFS) according to HER2 status. All statistical analyses were performed using SPSS® version 25 (IBM, Armonk, NY, USA). Results: In total, 108 patients were included; 10 (9.3%) had HER2-positive tumors. The ORR for patients with mCRC receiving standard chemotherapy did not differ for HER2-positive and HER2-negative tumors. The median PFS for patients with mCRC with HER2-positive or HER2-tumors after receiving first-line chemotherapy was 18.52 months [95% confidence interval (CI): 4.355-32.695] or 10.95 months (95% CI: 9.317-12.585; P=0.417), respectively, and that after second-line chemotherapy was 7.08 months (95% CI: 6.801-7.363) or 5.34 months (95% CI: 4.433-6.255; P=0.837), respectively. Likewise, OS did not differ according to HER2 expression (median OS: HER2-positive tumors, 49.1 months (95% CI: 0.000-98.365); HER2-negative tumors, 37.7 months (95% CI: 27.111-48.366; P=0.410). Conclusions: The tumor response and survival of patients with mCRC after standard chemotherapy did not differ by HER2 expression. These findings suggest that the status of HER2 expression need not be considered when choosing regimens as the current first- and second-line treatments.

Effect of silencing C-erbB-2 on esophageal carcinoma cell biological behaviors by inhibiting IGF-1 pathway activation.

OBJECTIVE: C-erbB-2 has been confirmed to be an oncogene that participates in cell growth, differentiation and division of tumors. We are wondered if its silenced expression can exert an anti-tumor effect. Therefore, this study is conducted to investigate the mechanism of C-erbB-2 silencing and IGF-1 pathway on esophageal carcinoma (EC) cell biological behaviors. METHODS: The objects of study were 84 EC patients from Heping Hospital Affiliated to Changzhi Medical College, with the collection of EC tissue and adjacent normal tissue (> 5 cm away from cancer tissue). C-erbB-2 protein expression in EC tissues was detected by immunohistochemistry. Human EC cell line Eca-109 was purchased from Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences. Based on different transfection protocols, EC cells with logarithmic growth phase of 3-5 passages were divided into blank control group, oe-C-erbB-2 NC group, siRNA C-erbB-2 NC group, oe-C-erbB-2 group, siRNA C-erbB-2 group, OSI-906 group, Rg5 group, Rg5 + siRNA C-erbB-2 NC group and Rg5 + siRNA C-erbB-2 group. Cell proliferation was detected by MTT assay; cell cycle distribution and apoptosis by flow cytometry; C-erbB-2, IGF-1, IGF-1R and Akt mRNA and protein expressions by qRT-PCR and western blot; and cell invasion and migration by Transwell assay and scratch test. Tumor growth was observed in male BALB/c nude mice (Shanghai Experimental Animal Center) based on Eca109 cell implantation, raising, and measurement. RESULTS: C-erbB-2, IGF-1, IGF-1R and Akt expression were higher in EC tissues than those in adjacent tissues (all P < 0.05). Compared with blank control group, both si-C-erbB-2 and OSI-906 groups had decreased IGF-1, IGF-1R and Akt mRNA and protein expressions, decreased cell proliferation, migration and invasion, prolonged G0/G1 phase, shortened S phase, increased cell apoptosis, and inhibited tumor growth (all P < 0.05); while opposite trends were detected in C-erbB-2 vector and Rg5 groups (all P < 0.05), without statistical differences in siRNA C-erbB-2 + Rg5 group (all P > 0.05). CONCLUSION: Silencing C-erbB-2 expression may inhibit EC cell proliferation, promote cell apoptosis and block cell cycle progression by inhibiting IGF-1 pathway activation. The beneficial effect of silencing C-erbB-2 expression can be reversed by promoting the activation of IGF-1 pathway. Findings in our study may provide potential reference for understanding the molecular mechanism of EC and supply possible axis for preventing the development of EC from the perspective of molecular biology.

Treatment Landscape and Prognosis After Treatment with Trastuzumab Emtansine.

Purpose Pertuzumab and T-DM1 are two efficient anti-HER2 treatments for patients with HER2-positive advanced breast cancer. While pertuzumab is usually given in first-line treatment and T-DM1 in second-line treatment, standard therapy options seem to be exhausted up to now after the treatment of patients with these two therapy options. Therefore, it is important to have data that describes the therapy situation and prognosis after T-DM1 treatment. Methods The PRAEGNANT metastatic breast cancer registry (NCT02338167) is a prospective registry for breast cancer patients with a focus on molecular biomarkers. Patients of all therapy lines with any kind of treatment are eligible. Collected data comprises therapies, adverse events, quality of life and other patient reported outcomes. Here we report on the patient characteristics and descriptive prognostic data for HER2-positive patients who have completed a treatment with T-DM1. Therapy patterns after T-DM1 and progression-free survival are reported as well as overall survival. Results A total of 85 patients were identified for the study who were prospectively observed during therapy after the termination of T-DM1. The main reason for T-DM1 termination was progress. Following T-DM1, lapatinib, trastuzumab and chemotherapy were the main therapy choices. Median progression-free survival was 4.8 months (95% CI: 3.2 - 6.3) and median overall survival was 18.4 months (95% CI: 15.5 - 21.3). Conclusions Therapy options after T-DM1 in a real-world setting seem to exhibit a relevant clinical efficacy, supporting the concept of continuous anti-HER2 treatments in the advanced therapy setting for breast cancer patients. Novel therapies are needed to improve the rather short median progression-free survival.

Impact of the Updated Guidelines on Human Epidermal Growth Factor Receptor 2 (HER2) Testing in Breast Cancer.

PURPOSE: In 2007, the American Society of Clinical Oncology and the College of American Pathologists had established a human epidermal growth factor receptor 2 (HER2) testing guideline, which was updated in 2013 and subsequently in 2018. We assessed the clinical impact of the recent update by comparing the in situ hybridization (ISH) results based on the 2007, 2013, and 2018 guidelines. METHODS: We assessed 2 cohorts. The first cohort included 1,161 primary invasive breast cancer (IBC) samples including 18 bilateral IBC cases, with both immunohistochemistry (IHC) and silver-enhanced ISH (SISH) results available for the HER2 status. The second cohort included 160 IBC cases with equivocal HER2 IHC, assessed using SISH. We retrospectively evaluated and compared the HER2 SISH results. RESULTS: There were 22 (1.9%) and 20 (12.5%) cases with altered SISH results according to the 2013 guidelines in cohorts 1 and 2, respectively. As per the 2018 guidelines, final HER2 statuses of 16 (1.4%) and 14 (8.5%) cases changed in cohorts 1 and 2, respectively. The 2013 guidelines increased the positive rate compared to the 2007 guidelines, in both cohorts (0.6% and 6.2%, respectively). Most equivocal cases in cohorts 1 (92.3%) and 2 (100%) as per the 2013 guidelines were reclassified as HER2-negative according to the 2018 guidelines. The 2018 guidelines increased the negative rates (1.3% in cohort 1 and 8.7% in cohort 2) and slightly decreased the positive rates (-0.2% in cohort 1 and -3.1% in cohort 2), compared to the 2013 guidelines. With each update, minor changes in the positive and negative rates were observed in whole breast cancer samples (cohort 1). However, the 2018 guidelines affected previously defined HER2-positive IBC with equivocal IHC results. CONCLUSION: Under the 2013 guidelines, the positive and equivocal cases increased. However, the 2018 guidelines eliminated ambiguous cases by reclassifying them as HER2-negative.

Progression-Free Survival and Overall Survival in Patients with Advanced HER2-Positive Breast Cancer Treated with Trastuzumab Emtansine (T-DM1) after Previous Treatment with Pertuzumab.

The approval of trastuzumab emtansine (T-DM1) was conducted without pertuzumab as previous therapy. Efficacy data on T-DM1 following pertuzumab treatment are therefore limited. This study explores this issue in a real-world setting. Within the prospective PRAEGNANT (Prospective Academic Translational Research Network for the Optimization of the Oncological Health Care Quality in the Advanced Setting) metastatic breast cancer registry (NCT02338167), patients in all therapy lines receiving any kind of treatment were eligible for inclusion. This report describes patient characteristics and progression-free survival (PFS) in human epidermal growth factor receptor 2 (HER2)-positive patients receiving T-DM1 after pertuzumab treatment. Seventy-six patients were identified, 39 of whom received T-DM1 as second-line therapy, 25 as third-line, and 12 as fourth-line therapy or higher. Pertuzumab was mostly administered as a first-line treatment (n = 61; 80.3%). The median PFS in all patients was 3.5 months (95% CI: 2.8-7.8); in second-line treatment, 7.7 months (95% CI: 2.8-11.0); in third-line, 3.4 months (95% CI: 2.3-not reached (NR)); and in fourth-line therapy or higher, 2.7 months (95% CI: 1.2-NR). T-DM1 was mainly administered second-line after pertuzumab, but also in more heavily pretreated patients. The PFS in higher therapy lines appears to be shorter than in second-line.

Detection and analysis of multiple biomarkers in ovarian cancer: clinical significance in diagnosis, treatment, and prognosis evaluation.

BACKGROUND: The purpose of this study was to explore the clinical significance of CA125, CK7, CK20, ER, PR, C-erbb2, and P-gp in ovarian cancer. METHODS: Ovarian cancer patients were recruited from Nantong Cancer Hospital between March 2006 and July 2011. The expressions of CA125, CK7, CK20, ER, PR, C-erbb2, and P-gp were determined by immunohistochemistry (IHC).The chi-square test (χ2) was used to analyze the correlation between each index and the clinical characteristics of the patients. The patients were followed up to record the cancer recurrence time. The Kaplan-Meier method was used to map the cumulative recurrence-free survival (RFS) rate, and COX regression analysis was established for multivariate analysis. RESULTS: The results of IHC showed that the positive expression rates of CA125, CK7, ER, C-erbb2, and P-gp in malignant ovarian cancer tissues were significantly higher than those in benign ovarian cancer tissues. CA125 expression in malignant ovarian cancer was significantly correlated with the age of patients and the Federation of International Gynecology and Obstetrics (FIGO) stage. CK7 expression in malignant ovarian cancer was significantly correlated with the age, tissue differentiation, and number of residual lesions. CK20 expression in malignant ovarian cancer was significantly correlated with the age and tissue differentiation of the patients. ER expression in malignant ovarian cancer was significantly correlated with the age of patients and FIGO stage. PR expression in malignant ovarian cancer was significantly correlated with the age of the patients. C-erbb2 expression in malignant ovarian cancer was significantly correlated with the age of the patients. P-gp expression in malignant ovarian cancer was significantly correlated with the patient age, pathological type, and tissue differentiation. The expression of CA125, CK7, CK20, C-erbb2, and P-gp had significant effects on the prognosis of patients with ovarian cancer. The COX regression analysis showed that P-gp was an independent risk factor for ovarian cancer. CONCLUSIONS: In malignant ovarian cancer tissues, CA125, CK7, CK20, ER, PR, C-erbb2, and P-gp are over-expressed. The expression of P-gp is an independent risk factor for ovarian cancer, and it can be an important target for the treatment of malignant ovarian cancer.

Ultrasound microbubble-mediated CRISPR/Cas9 knockout of C-erbB-2 in HEC-1A cells.

OBJECTIVE: Epidermal growth factor receptor 2 (C-erbB-2) is one of the most frequently mutated oncogenes in human tumors. We aimed to evaluate the knockout efficiency of clustered regularly interspaced short palindromic repeat (CRISPR) technology using ultrasound microbubble transfection to target C-erbB-2 in human endometrial cancer (HEC)-1A cells. METHODS: Three single guide RNAs (sgRNAs) targeting C-erbB-2 were designed and used to construct CRISPR/CRISPR-associated (Cas)9-C-erbB-2 plasmids. The constructed plasmids were transfected into HEC-1A cells using ultrasound microbubbles. C-erbB-2 knockout cloned cells were identified by green fluorescence. C-erbB-2 mRNA and protein expression was measured by reverse transcription (RT)-PCR and western blotting, respectively. RESULTS: RT-PCR showed that C-erbB-2 mRNA expression was significantly lower in sgRNA1-transfected cells (0.57 ± 0.06) than in blank (1.00 ± 0.09) and negative-control groups (1.02 ± 0.12). Western blotting revealed C-erbB-2 protein expression to be significantly lower in sgRNA1-transfected cells (0.269 ± 0.033) than in blank (0.495 ± 0.059) and negative-control groups (1.243 ± 0.281). However, there was no significant difference in C-erbB-2 protein and mRNA expression in sgRNA2- and sgRNA3-transfected cells compared with controls. CONCLUSION: Ultrasound microbubbles can mediate plasmid transfer into HEC-1A cells to interfere with gene expression and knockout C-erbB-2.

Expression of HER2/c-erbB-2, EGFR Protein in Gastric Carcinoma and its Clinical Significance.

OBJECTIVE: To investigate the HER2/c-erbB-2, epidermal growth factor receptor (EGFR) protein expression in gastric cancer and association with patients' clinical pathology characteristics and prognosis. METHODS: HER2/c-erbB-2 and EGFR protein expression was examined by immunohistochemical assay in gastric cancer tissue and corresponding paired normal gastric tissue of 67 patients of gastric carcinoma. The HER2/c-erbB-2, EGFR protein positive expression rate in cancer tissue and normal gastric tissue were compared. The correlation between HER2/c-erbB-2, EGFR protein positive expression and patients' clinical pathology characteristics and survival was evaluated. RESULTS: The positive expression rate of HER2/c-erbB-2 in the cancer and paired normal gastric tissues were 32.8% (22/67) and 4.5% (3/67), respectively with statistical difference (p<0.05). And the positive expression rate of EGFR in cancer and paired normal gastric tissues were 41.8% (28/67) and 5.9 (4/67), respectively, with statistical difference (p<0.05). HER2/c-erbB-2 positive expression in cancer tissue was significant correlated with the pathology grading (p<0.05), tumor invasion depth (p<0.05) and local regional lymph node metastasis (p<0.05); EGFR positive expression in cancer tissue was significant correlated with the tumor invasion depth (p<0.05) and local regional lymph node metastasis (p<0.05). The median survival time was 13.14 and 23.6 months respectively for HER2/c-erbB-2 positive and negative expression groups respectively with statistical difference ( HR=2.26, 9%CI:1.06-4.80, p<0.05). However, the median survival time was 15.47 and 22.87 months for EGFR positive and negative expression groups respectively, without statistical difference (HR=1.78, 9%CI:0.96-3.29, p>0.05). CONCLUSION: Positive expression of HER2/c-erbB-2 and EGFR proteins in cancer tissue was significant higher than normal gastric tissue and have significant correlation with prognosis.

Therapy Landscape in Patients with Metastatic HER2-Positive Breast Cancer: Data from the PRAEGNANT Real-World Breast Cancer Registry.

This study presents comprehensive real-world data on the use of anti-human epidermal growth factor receptor 2 (HER2) therapies in patients with HER2-positive metastatic breast cancer (MBC). Specifically, it describes therapy patterns with trastuzumab (H), pertuzumab + trastuzumab (PH), lapatinib (L), and trastuzumab emtansine (T-DM1). The PRAEGNANT study is a real-time, real-world registry for MBC patients. All therapy lines are documented. This analysis describes the utilization of anti-HER2 therapies as well as therapy sequences. Among 1936 patients in PRAEGNANT, 451 were HER2-positive (23.3%). In the analysis set (417 patients), 53% of whom were included in PRAEGNANT in the first-line setting, 241 were treated with H, 237 with PH, 85 with L, and 125 with T-DM1 during the course of their therapies. The sequence PH → T-DM1 was administered in 51 patients. Higher Eastern Cooperative Oncology Group (ECOG) scores, negative hormone receptor status, and visceral or brain metastases were associated with more frequent use of this therapy sequence. Most patients received T-DM1 after treatment with pertuzumab. Both novel therapies (PH and T-DM1) are utilized in a high proportion of HER2-positive breast cancer patients. As most patients receive T-DM1 after PH, real-world data may help to clarify whether the efficacy of this sequence is similar to that in the approval study.

Correlation between ultrasonic features and expression levels of C-erbB-2, VEGF and nm23 in breast cancer.

Breast cancer is one of the most common female malignancies in clinical practice, which ranks number one in terms of its high incidence. We investigated the relevance of ultrasonic features of breast cancer and expression levels of C-erbB-2, vascular endothelial growth factor (VEGF) and nm23 and its clinical significance. A total of 76 patients with breast cancer were recruited who were admitted to The Affiliated Hospital of Qingdao University from January, 2016 to August, 2017. All patients underwent color Doppler ultrasonic imaging, and expression levels of C-erbB-2, VEGF and nm23 in their tumor tissues were measured by immunohistochemistry. The ultrasonic features were evaluated and compared with the expression levels of C-erbB-2, VEGF and nm23 for each patient. Ultrasonography showed a tumor mass with spiculated margins, abnormal vasculature, and a diameter no less than 3 cm, as well as lymph node metastasis. The above signs were associated with high expression of C-erbB-2, VEGF and nm23 (p<0.05), but calcification was not associated with high expression of these biomarkers (p>0.05). For patients with highly expressed C-erbB-2 and VEGF, the time to peak (TTP) of the time-intensity curve obtained by contrast enhanced ultrasound was shorter, while the peak intensity (PI) was higher. On the contrary, for patients with highly expressed nm23, the TTP was apparently longer, while the PI was lower (p<0.05). The ultrasonic features of breast cancer were relevant to the expression levels of C-erbB-2, VEGF and nm23. Thus, the expression levels of C-erbB-2, VEGF and nm23 were predictable indirectly according to the ultrasonic features of the patient, which can be used as a reference for breast cancer treatment and prognosis prediction.

Expression of p53, epidermal growth factor receptor, c-erbB2 in oral leukoplakias and oral squamous cell carcinomas.

BACKGROUND: Oral cancer is a leading cause of cancer in India and contributes to 12% deaths worldwide. The identification of high-risk oral premalignant lesions such as leukoplakia and intervention at premalignant stages could result in significant loss of mortality and morbidity among these patients. The most frequently observed genetic aberrations in these lesions are of mutations in p53, c-erbB2, and epidermal growth factor receptor (EGFR). No specific tumor markers have been identified consistently in oral leukoplakias and the available studies show wide variations in their expression. MATERIALS AND METHODS: A total of eighty cases were taken up for study which included forty cases of leukoplakia and forty cases of squamous cell carcinomas (SCCs). RESULTS: There was a significant correlation between the expression of markers p53 and EGFR in leukoplakia and SCC. The expression of p53 was correlated between leukoplakia, SCC, and control and was found to be significant (P ≤ 0.001). Similarly, EGFR expression was significant (P ≤ 0.001) between cases of leukoplakia, SCCs, and controls. c-erbB2 was found to be negative though cytoplasmic positivity was observed in a few cases. Similarly, in SCCs, it was observed that lesser the differentiation, more is the expression of both p53 and EGFR. Similarly, a definite correlation was observed between p53 and EGFR (P ≤ 0.001) but not with c-erbB2 (P ≤ 1.000). CONCLUSION: Thus, the author concludes that p53 and EGFR are useful biomarkers for the diagnosis of leukoplakia and their risk of malignant transformation.

Expression of EGF receptors in canine prostate with proliferative inflammatory atrophy and carcinoma / Expressão de receptores EGF na próstata canina com atrofia inflamatória proliferativa e carcinoma

ABSTRACT: Gene expression of ErbB1 and ErbB2, and immunostaining of EGFR (Her1) and Her2 (c-erbB-2) were evaluated in this study to ascertain whether these receptors are involved in the evolution of canine premalignant and malignant prostatic lesions, as proliferative inflammatory atrophy (PIA) and prostatic carcinoma (PC). With regards to the intensity of EGFR immunostaining, there was no difference between normal prostatic tissue and tissues with PIA or PC. In relation to Her2 immunostaining, there were differences between normal prostatic tissue and those with PIA and PC, as also differences between prostates with PIA and PC. There was no correlation between EGFR and Her2 immunostaining. ErbB1 gene product was detected in two normal tissue samples, in one with PIA, and in all samples with PC. ErbB2 mRNA was recorded in two canine samples with PIA, in all with PC, but was not detected in normal prostatic tissue. It was concluded that EGFR and Her2 play roles in canine PIA and PC, suggesting that those receptors may be involved in canine prostatic carcinogenesis.

RESUMO: A expressão gênica de ErbB1 e ErbB2 e a imunomarcação de EGFR (Her1) e Her2 (c-erbB-2) foram avaliadas para verificar o envolvimento desses receptores em lesões pré-malignas e malignas da próstata canina, como a atrofia proliferativa inflamatória (PIA) e o carcinoma prostático (PC). Em relação à intensidade de imunomarcação para EGFR, não houve diferença entre o tecido prostático normal e com PIA e PC. Em relação a Her2, observou-se diferença de imunomarcação entre o tecido prostático normal e aqueles com PIA e PC e entre os com PIA e PC. Não houve correlação entre EGFR e Her2. O gene ErbB1 foi detectado em duas amostras normais, uma de PIA e em todas as amostras de PC. O gene ErbB2 foi detectado em duas amostras de PIA e em todas as amostras de PC, não sendo detectado no tecido prostático normal. Conclui-se que EGFR e Her2 atuam nas lesões de PIA e PC, sugerindo o envolvimento destes na carcinogênese da próstata canina.

C-erbB-2 expression is related with pathological progression of gastric cancer: results of a non-radioactive in situ hybridization.

OBJECTIVE: To study the relationship of c-erbB-2 oncogene expression with major pathological characteristics of gastric cancer (GC) progression. METHODS: Eighty-one GC specimens were studied for c-erbB-2 oncogene amplification using non-radioactive in situ hybridization method. The c-erbB-2 overexpression status was correlated with tumor differentiation, tumor invasion and lymph node metastasis. RESULTS: Among the 81 pathology confirmed GC patients, 41 (50.6%) were found to have c-erbB-2 overexpression in cancer tissues. The rate of c-erbB-2 overexpression was significantly higher in those with poor tumor differentiation (63.0%, 29/46) than in those with well differentiated tumor (34.3%, 12/35) (χ 2=6.576, P<0.001); significantly higher in those that invaded into deep muscle and beyond (55.7%, 39/70) than in those with tumors limited to the superficial muscle (18.2%, 2/11) (χ 2=5.357, P<0.025); and significantly higher in those with lymph node metastases (59.6%, 34/57) than in those without lymph node involvement (29.2%, 7/24) (χ 2=6.278, P<0.025). CONCLUSIONS: c-erbB-2 oncogene overexpression may indicate a more aggressive biological behavior of the tumor and could be used as a predictive marker for GC pathological progression.

Correlation between peripheral nutrient artery and expression of C-erbB-2 in breast invasive ductal carcinoma / 中华超声影像学杂志

Objective To evaluate the relation between peripheral nutrient artery and expression of C-erbB-2 in breast invasive ductal carcinoma(IDC) . Methods The peak systolic velocity(PSV) and resistive index ( RI ) of peripheral nutrient artery of tumor in 122 cases with breast IDC and 138 cases with fibroadenoma which proved by operation and pathology were analyzed retrospectively . The C-erbB-2 was measured by immunohistochemical test ,according to the results of immunohistochemical examination ,the masses were divided into negative group( -) ,weakly positive group( + ) ,positive group( + + ) and strong positive group( + + + ) . The relationship between the classification of C-erbB-2 expression and the two factors of peripheral nutrient artery in breast tumor mass were analysed . Results The PSV of trophoblastic artery in IDC group was ( 20 .99 ± 8 .14 ) cm/s , RI 0 .66 ± 0 .07 , the PSV of trophoblastic artery in fibroadenoma group was (15 .56 ± 3 .68)cm/s ,RI 0 .66 ± 0 .07 ,there was significant statistically difference in peripheral nutrient artery of tumor between the breast IDC and fibroadenoma( P < 0 .001) . The RI and PSV of the peripheral nutrient artery in IDC were correlated to the classification of C-erbB-2 expression ( r=0 .323 ,0 .360 ,respectively) ,there was no correlation between the RI and PSV of peripheral nutrient artery in fibroadenoma and the classification of C-erbB-2 expression ( r = 0 .001 ) . Conclusions The spectrum form of peripheral nutrient artery in IDC is high speed and high resistance . The RI and PSV of the peripheral nutrient artery in IDC are correlated to the classification of C-erbB-2 expression .

Expression of DOG-1 and C-erbB-2 in papillary thyroid carcinoma and their clinical significance / 临床与实验病理学杂志

Purpose To investigate the expression and clinical significance of DOG-1 and C-erbB-2 in papillary thyroid carcinoma.Methods Immunohistochemical SP method was used to detect the expression of DOG-1 and C-erbB-2 protein in 48 cases of papillary thyroid carcinoma and 30 cases of benign thyroid lesions (15 cases of nodular goiter and 15 cases of Hashimoto's thyroiditis).Results The DOG-1 positive rate of thyroid papillary carcinoma (27.08％,13/48) was significantly higher than that of benign lesions (0,0/30),the difference was significant (P ＜ 0.05).The C-erbB-2 positive rate (39.58％,19/48) was significantly higher than that of benign lesions (3.33％,1/30),the difference was significant (P ＜ 0.05).Positive expression of DOG-1 as well as C-erbB-2 correlated with advanced TNM and presence of lymph node metastasis.The expression of DOG-1 and C-erbB-2 in patients with multifocal carcinomas combined with lymphatic metastasis showed a significant positive correlation(r =0.503,P =0.024).Conclusion The data suggest that DOG-1 and C-erbB-2 contribute to the pathogenesis and progress of thyroid papillary carcinoma.Our results introduce DOG-1 combined with C-erbB-2 as a promising biomarker for recurrence prediction and target therapy.

Immunohistochemistry Study of P53 and C-erbB-2 Expression in Trophoblastic Tissue and Their Predictive Values in Diagnosing Malignant Progression of Simple Molar Pregnancy.

BACKGROUND: Finding a tumor marker to predict the aggressive behavior of molar pregnancy in early stages has yet been a topic for studies. OBJECTIVES: In this survey we planned to study patients with molar pregnancy to 1) assess the p53 and c-erbB-2 expression in trophoblastic tissue, 2) to study the relationship between their expression intensity and progression of a molar pregnancy to gestational trophoblastic neoplasia, and 3) to determine a cut off value for the amount of p53 and c-erbB-2 expression which might correlate with aggressive behavior of molar pregnancy. PATIENTS AND METHODS: In a prospective cross sectional study by using a high accuracy technique EnVision Tm system for immunohistochemistry staining of molar pregnancy samples, we evaluated p53 and c-erbB-2 expression in cytotrophoblast and syncytiotrophoblast and the correlation of their expression with progression of molar pregnancy to gestational trophoblastic neoplasia (GTN). Normal prostatic tissue and Breast cancer tissue were used as positive controls. RESULTS: We studied 28 patients with simple molar pregnancy (SMP) and 30 with GTN. Cytotrophobalst had significantly higher expression of p53 and c-erbB-2 and syncytiotrophoblast had greater expression of p53 in GTN group as compared to SMP group. The cut off values for percentage of p53 positive immunostained cytotrophoblast and syncytiotrophoblast were 5.5% and 2.5%. In c-erbB-2 positive membranous stained cytotrophoblast the cut off was 12.5%. CONCLUSIONS: Our data suggests that over expression of p53 and c-erbB-2 is associated with malignant progression of molar pregnancy. We encountered that high expression of p53 and c-erbB-2 in trophoblastic cells could predict gestational trophoblastic neoplasia during the early stages.

Significance of serum c-erbB-2 oncoprotein, insulin-like growth factor-1 and vascular endothelial growth factor levels in ovarian cancer.

OBJECTIVES: Our aim was to determine the predictive values of serum levels of several growth factors in ovarian cancer, including soluble c-erbB-2 oncoprotein, insulin-like growth factor-1 (IGF-1) and vascular endothelial growth factor (VEGF). BACKGROUND: Previous studies have shown that growth factors play an important role in carcinogenesis. METHODS: Two groups were established. One of them was the malignant group which included 41 patients with ovarian carcinoma and the other was the control group that was made up of 28 healthy volunteers. Preoperative serum samples were obtained from the patients, and c-erbB-2, IGF-1 and VEGF levels were measured in these samples using ELISA. Serum CA-125 levels were also determined, by chemiluminescent microparticle immunoassay. RESULTS: VEGF levels of the malignant group were significantly higher than those of the control group (p < 0.01). CA-125 levels were also significantly higher than the in control group (p < 0.001). Area under the ROC curve (AUC) was 0.982 for CA-125, 0.780 for VEGF, 0.603 for c-erbB-2, and 0.467 for IGF-1 in differentiating cancers from controls. CONCLUSION: Serum VEGF levels might be a predictor for diagnosis in ovarian cancer patients, while serum c-erbB-2 and IGF-1 levels do not have a clinical significance in terms of ovarian cancer (Tab. 1, Fig. 1, Ref. 46).

Metabolic landscape of advanced gastric cancer according to HER2 and its prognostic implications.

BACKGROUND: In advanced gastric cancer (AGC), HER2 is a validated therapeutic target. However, the metabolic landscape of AGC based on HER2 status has not been reported. Furthermore, the prognostic value of HER2 in AGC is under debate. The purpose of this study was to determine the metabolic landscape and prognosis on the basis of HER2 status in AGC. METHODS: We analyzed 866 AGC patients treated with palliative chemotherapy and whose HER2 status was evaluated. HER2 positivity was defined as HER2 IHC 3+ or HER2/CEP17 ratio ≥2. Among them, 363 patients were evaluated with (18)F FDG-PET before chemotherapy. We analyzed mSUV (maximal standardized uptake value) according to HER2 status and clinical outcomes. RESULTS: Among 866 patients, 225 (26.0 %) had HER2+ GC. The mSUV of HER2+ GC was significantly higher than that of HER2- GC (12.6 vs. 8.7, p < 0.001). Increased HER2 IHC positivity was correlated with increased mSUV (IHC-: 8.1, IHC 1+: 8.2, 2+: 11.4, 3+: 13.2, p < 0.001). Excluding HER2+ patients who received HER2-targeting agents, OS of patients was not different by HER2 status (12.5 vs. 11.9 months, p = 0.688). However, according to tumor metabolism, patients with higher mSUV showed worse OS regardless of HER2 positivity (mSUV < 12.8:14.8, ≥12.8:8.6 months, p < 0.001). CONCLUSION: Tumor metabolism of AGC adversely influenced OS under treatment with cytotoxic chemotherapy. Tumor metabolism was higher in HER2+ AGC than HER2-. However, HER2 was not a prognostic factor in patients who received chemotherapy without HER2-targeting agents.

Study of HB EGF,C-erbB-2 test in differential diagnosis of ovarian benign and malignant tumor and determine the meaning of a complex condition / 国际检验医学杂志

Objective To study HB‐EGF ,C‐erbB‐2 test in differential diagnosis of ovarian benign and malignant tumor and de‐termine the meaning of a complex condition .Methods Totally 80 cases of patients with ovarian tumors were collected from August 2014 to July 2015 ,including 20 cases benign ovarian tumor ,and 40 cases epithelial ovarian cancer ,13 cases of Ⅰ period ,Ⅱ period in 14 cases ,Ⅲ ~ Ⅳ period 13 cases .At the same time ,normal endometrium ovarian tissue from 30 cases volunteers were collected .HB EGF ,C‐erbB‐2 expression in ovarian tissue were detected by using flow cytometry .The immune histochemical method was used to detect C‐erbB‐2 expression from 40 examples carcinoma ,30 cases of normal endometrium intrauterine membrane .Results The rate of positive cells of HB‐EGF ,C‐erbB‐2 was significantly higher than that of benign ovarian tumor(P< 0 .05) ;C‐erbB‐2 for lower ex‐pression in normal endometrium ,endometrial carcinoma in content was higher than the normal uterus express ,the difference was statistically significant(P< 0 .05) ;Endometrial cancer of different pathological staging ,C‐erbB‐2 expression was different also ,in‐cluding C‐erbB‐2 expression in endometrial carcinoma of stage Ⅰ ,Ⅱ significantly below Ⅲ ,Ⅳ period ,the difference was statistical‐ly significant(P< 0 .05) .Conclusion The high expression of C‐erbB‐2 protein is associated with the occurrence and development of endometrial carcinoma ,C‐erbB‐2 testing could help to clinically evaluate the biological behavior and prognosis of endometrial carci‐noma .

Expression of C-erbB-2 in sinonasal squamous cell cancer cells and its significance / 军事医学

Objective To analyze the expressions and clinical significance of human epidermal growth factor receptor-2 (C-erbB-2) protein in sinonasal squamous cell cancer cells.Method Immunohistochemical and RT-PCR methods were used to detect the expression of C-erbB-2 in 62 cases of sinonasal squamous carcinoma tissues,30 cases of nasal polyps and 25 cases with normal nasal mucosa.The relationships between the expression of C-erbB-2 in sinonasal squamous carcinoma tissues and clinical pathological characteristics were analyzed.Results There was significant difference in the expression of C-erbB-2 in sinonasal squamous carcinoma tissues, nasal polyps and normal nasal mucosa tissues(P <0.05).The expression of C-erbB-2 was positively correlated with the clinicopathologic stage, tumor classification and lymph node involvement(P<0.05).Conclusion The expression of C-erbB-2 is correlated with tumorigenesis,invasion and metastasis of sinonasal squamous cell carcinoma.It can be used as an auxiliary diagnostic and prediction maker as well as a new therapeutic target of sinonasal squamous cell cancer.