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Biliary tract cancers (BTC) are highly heterogeneous tumours. Currently, the global demand for advanced BTC treatment is far from being met, and the survival benefit from advanced chemotherapy is limited. In recent years, with the rise of precision treatment, there are more and more treatment options available for advanced BTC. Human epidermal growth factor receptor-2 (HER2) inhibitors, including monoclonal antibodies, tyrosine kinase inhibitors, antibody drug conjugates, and bispecific antibodies, have been explored in BTC. This article reviews the research progress and prospects of HER2 inhibitors in BTC in recent years, so as to provide a better clinical guidance.
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Objective:To study the amplification / overexpression of human epidermal growth factor receptor 2 (HER2) in patients with gallbladder cancer, and to analyze the correlation between amplification/overexpression of HER2 with clinicopathological features and survival in patients after R 0 resection. Methods:There were 14 males and 26 females, aged (60.3±8.7) years old and treated at the Cancer Hospital of Chinese Academy of Medical Sciences from January 2011 to December 2016 who met the inclusion criteria of the study. Immunohistochemistry and fluorescence in situ hybridization were used to detect amplification / expression of HER2 in resected tumor tissues. Patients were divided into two groups according to the HER2 gene expression: the HER2-negative group ( n=40) and the HER2-positive group ( n=10). The Chi-square test was used to analyze the relationship between amplification/expression of HER2 and clinicopathological parameters. Patients were followed up by telephone for prognosis. The Kaplan-Meier method was used for survival analysis. The Cox proportional hazard model was used to explore factors affecting prognosis of gallbladder cancer patients. Results:HER2 amplification/overexpression was found in 10 patients with gallbladder cancer, with a positive rate of HER2 being 20.0% (10/50). There was a significant difference in the proportion of patients with vascular tumor thrombus between the HER2 negative group and the HER2 positive group [7.5%(3/40) vs. 30.0%(3/10), P<0.05]. On follow-up, data of 46 patients was available. There were 36 patients in the HER2-negative group and 10 patients in the HER2-positive group. Compared with the HER2-negative group, the median recurrence-free survival (10.10 vs. 75.07 months) and the median overall survival (16.77 vs. 83.07 months) of the HER2-positive group were both significantly lower (both P<0.05) than the HER2-negative group. Univariate analysis showed HER2 positivity to be a risk factor for recurrence-free and overall survival in patients with gallbladder cancer after radical resection. Cox multivariable analysis revealed that lymph node metastasis was an independent risk factor for both recurrence-free ( HR=4.31, 95% CI: 1.92-9.68, P<0.001) and overall survival ( HR=3.44, 95% CI: 1.08-11.00, P=0.037). Conclusion:Amplification / overexpression of HER2 was associated with venous invasion and worse prognosis in patients with gallbladder cancer.
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RESUMEN Introducción: El carcinoma mamario negativo a la expresión de receptores hormonales (RH negativo) incluye los subtipos moleculares Her-2/neu y triple negativo, asociados ambos a una mayor actividad biológica del tumor y un pronóstico desfavorable. Objetivo: Determinar la incidenciade los carcinomas triples negativos y Her-2/neu en carcinomas mamarios y su relación con variables clínico-patológicas de valor pronóstico. Métodos: Se realizó unestudio descriptivo, de corte transversal, en el Hospital Celestino Hernández, Villa Clara, entre enero de 2017 a junio de 2019. Se incluyeron 293 mujeres con diagnóstico de carcinoma de mama infiltrante, a cuyas biopsias se les realizó estudio inmunohistoquímico determinando la incidencia de los subtipos moleculares triple negativo y Her2/neu y su relación con otras variables de valor pronóstico. Resultados: En la serie se determinó la incidencia de los subtipos moleculares triples negativo y Her2/neu. En ambos subtipos moleculares, más de las dos terceras partes de las pacientes fueron mayores de 50 años, presentaron tallas tumorales mayor de 2 cm en el momento del diagnóstico y tuvieron histología ductal. Destaca además la relación de ambos subtipos moleculares con formas histológicas moderada y pobremente diferenciadas del carcinoma mamario. De igual forma, en ambos subtipos, el índice de proliferación determinado por Ki67 fue alto en más de las dos terceras partes de las pacientes estudiadas. Conclusiones: La edad posmenopáusica, el tipo histológico ductal, el grado histológico alto, el alto índice de Ki67 y la talla tumoral mayor de 2 cm se asocian con frecuencia a subtipos moleculares del carcinoma mamario negativos a receptores hormonales.
ABSTRACT Introduction: The breast carcinoma which is negative to the expression of hormonal receptors (negative RH) includes the molecular subtypes Her2/neu and triple negative, that are both associated to higher biological activity and a worse forecast. Objective: To determine the real incidence of the subtypes triple negative and Her2/neu in breast carcinoma and its correlation with prognostic value clinic-pathological variables. Methods: A descriptive, cross-sectional study was done in the Hospital Celestino Hernández, Villa Clara, from January 2017 to June 2019. It was included 293 women with diagnosis of infiltrating breast carcinoma, whose biopsies were studied by immunohistochemistry, determining the incidence of the molecular subtypes triple negative and overexpression of Her-2 and its correlation with others prognostic value variables. Results: In the series it was determined the incidence of the molecular subtypes triple negative and Her2/neu. In both molecular subtypes more two third of patients were older than 50 years old, had tumor size larger than 2 cm at the moment of diagnosis and had ductal histology. The correlation of the both molecular subtypes with moderately and poorly histological types of breast carcinoma stands out. In the same way the proliferation index determined by Ki67 was high in more two third of the studied patients. Conclusions: The post-menopausal age, the ductal histologic type, high histologic grade, high index of Ki67 and tumor size larger than 2 cm are often associated to molecular subtypes of breast carcinomas which are negative to the expression of hormonal receptors.
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Several studies have shown that human epidermal growth factor receptor 2 (HER2) amplification could be a predictive biomarker of resistance to anti-epidermal growth factor receptor monoclonal antibodies in patients with RAS wild-type metastatic colorectal cancer (mCRC). Dual HER2 inhibition with trastuzumab plus lapatinib or pertuzumab has shown promising preliminary anti-tumoral efficacy in RAS wild-type mCRC. HER2-targeted therapeutic strategies have the potential to change the treatment paradigm for a clinically relevant subgroup of patients with mCRC.
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Objective:To investigate the correlation of PELP1/MNAR expression with expressions of estrogen receptor (ER), Ki-67, human epidermal growth factor receptor 2 (HER2) and PIK3CA gene mutation.Methods:A total of 80 paraffin-embedded tissue specimens of primary invasive breast cancer patients in the Fifth People's Hospital of Datong in Shanxi Province from January 2008 to December 2018 were collected. The expression of PELP1/MNAR was examined by immunohistochemistry EliVision tow-step method. The polymerase chain reaction (PCR)-Sanger sequencing method was used to detect the mutation of PIK3CA gene. The expressions of PELP1/MNAR among patients with different expression status of ER, Ki-67, HER2 and with or without PIK3CA gene mutation were compared, and the correlations between each index and the expression of PELP1/MNAR were analyzed.Results:The high expression rates of PELP1/MNAR protein in patients with ER-positive [86.1% (31/36) vs. 59.1% (26/44)], Ki-67 high expression [100.0% (13/13) vs. 65.7% (44/67)], HER2-positive [81.0% (34/42) vs. 60.5% (23/38)] were high, and the differences were statistically significant (all P<0.05). There was no significant difference in the high expression rate of PELP1/MNAR protein between patients with mutant and wild-type PIK3CA [60.0% (12/20) vs. 75.0% (45/60), P = 0.199]. The expression of PELP1/MNAR was negatively correlated with the expression level of ER ( r = -0.195, P < 0.05), positively correlated with the expression level of Ki-67 ( r = 0.198, P < 0.05), positively correlated with the expression level of HER2 ( r = 0.225, P < 0.05), and negatively correlated with lymph node metastasis ( r = -0.269, P < 0.05). Conclusions:The expression of PELP1/MNAR in invasive breast cancer is negatively correlated with the expression level of ER, and positively correlated with the expression level of Ki-67 and HER2. There is no correlation between PELP1/MNAR expression and PIK3CA gene mutation, and the two may play their own role in the PI3K-AKT-mTOR regulatory pathway of breast cancer.
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Objective@#To investigation HER2 status in gastric adenocarcinoma of Chinese and contributing factors to the HER2 expression. @*Methods@#HER2 status of 40 842 gastric adenocarcinomas and clinical data were retrospectively collected from 23 hospitals dated from 2013 to 2016. The association between HER2 positivity and clinicopathologic features was analyzed. @*Results@#Of the 40 842 patients the median age was 62 years, the male female ratio was 2.6∶1.0. The rate of HER2 positivity was 8.8% (3 577/40 842). HER2 expression was related to the tissue type, tumor location, Lauren classification and tumor differentiation (P values: 0.009, 0.001, <0.01 and <0.01, respectively). Different HER2 expression status was observed between primary and recurrent tumors in 7.6% (48/635) cases. The rates of HER2 positivity ranged from 2% to 10% among different institutions. The rates of HER2 FISH amplification were dramatically different among the 23 hospitals (0-100%) with an average rate of 10% (810/8 156) in patients with HER2 IHC 2+ . @*Conclusions@#HER2 expression is associated with clinicopathologic characteristics. HER2 re-assessment of tumor tissue and use of in situ hybridization techniques increase HER2 positivity. The current retrospective study should reflect the HER2 status in gastric adenocarcinoma of Chinese patients.
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Objective@#To investigate human epidermal growth factor 2 (HER2) gene status and in situ mRNA expression in breast cancers with immunohistochemistry(IHC) 1+ , and to reveal HER2 positive rate in these patients to provide reference data for obtaining precise HER2 results and modifying relevant clinical strategy to breast cancer.@*Methods@#Sixty-five IHC 1+ formalin-fixed and paraffin-embedded samples of invasive breast carcinoma of no special type (IBC-NST) were collected by surgical operation at Peking Union Medical College Hospital during 2011 to 2013. HER2 status and in situ mRNA expression were tested by fluorescence in situ hybridization (FISH) and RNAscope, respectively, by using tissue microarray. Metastatic lymph node was re-tested by FISH if HER2 status was equivocal or negative and with high expression of mRNA in the primary lesion.@*Results@#Four of 65 samples (6.2%) were FISH positive, which included 2 cases of HER2/CEP17>2 and average HER2 copy number>4 and 2 cases of HER2/CEP17<2 and average HER2 copy number>6. In the 4 samples of HER2 positive, 2 patients showed high in situ mRNA expression (3 scores by RNAscope), 2 patients showed moderate in situ mRNA expression (2 scores by RNAscope). In addition, 3 specimens with HER2/CEP17>2 and average HER2 copy number<4 were found in all patients, which included 2 cases of high in situ mRNA expression (3 and 4 scores by RNAscope) and 1 cases of moderate in situ mRNA expression (2 scores by RNAscope). There was no significant association between HER2 status or mRNA expression and clinicopathological characteristics, including tumor size, histopathological differentiation, lymph node metastasis and lymphovascular invasion (P>0.05).@*Conclusions@#A small number of HER2 IHC 1+ patients exist mRNA expression by using FISH method, which suggested that these patients might benefit from anti-HER2 therapy potentially. Since the importance for patients with breast cancers to develop diagnostic and therapeutic strategies from accurate molecular typing, further studies based on a larger cohort are needed to validate our findings.
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Objective@#To construct the third generation chimeric antigen receptor based on a novel humanized anti-HER2 H1-2 scFv, and to investigate the specific cytotoxicity of H1-2 CAR modified T lymphocytes(CAR-T) against HER2+ tumor cells.@*Method@#The expression cassette of the third generation CAR gene and anti-HER2 H1-2 scFv were constructed and cloned into lentivirus transfer plasmid, and then the third generation H1-2 CAR was transduced into human T lymphocytes using lentivirus.Enzyme linked immunosorbent assay was used to detect the expression of cytokines IL2, and LDH release assay was used to detect the cytotoxic effect of the H1-2 CAR-T.Finally, NOD/SCID mice and HER2+ breast cancer cell line SKBR3 were used to detect the anti-tumor effect of H1-2 CAR-T in vivo.@*Results@#The third generation H1-2 CAR was successfully constructed.H1-2 CAR-T secreted high dose of IL2 after confrontation with HER2+ breast cancer cells.In vitro, the cytolytic rate of H1-2 CAR-T on high expression HER2+ tumor cells was significantly higher than that in low expression HER2 or non-expression HER2 tumor cells. At the efficacy to target ratio of 20, the cytolytic rate of H1-2 CAR-T against breast cancer cell SK-BR-3 could reach (90.1±2.8)%, while the cytolytic rate of H1-2 CAR-T against HER2- breast cancer cell MDA-MB-231 was only (13.5±4.7)%. In the mouse xenograft tumor model, H1-2 CAR-T cells inhibited breast cancer growth in vivo.At the end of the experiments, the average tumor weight in the H1-2 CAR-T cell treatment group was (0.7±0.1) g, the non-transfected T cell therapeutic group was (1.2±0.2) g, and the PBS group was (1.2±0.2) g. There was significant difference between the H1-2 CAR-T therapeutic group and the non-transfected T cell therapeutic group (P<0.05). However, there was no significant difference between the non-transfected T cell therapeutic group and the PBS treatment group (P>0.05).@*Conclusion@#The HER2-sepcific H1-2 CAR-T cells specifically kill HER2 positive cells, and further studies on CAR-T cells for the treatment of HER2+ cancers are useful.
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Objective@#To study the clinical significance of HER2 overexpression and/or amplification in gallbladder adenocarcinoma.@*Methods@#HER2 staining was performed on 123 cases of gallbladder adenocarcinoma specimens by IHC using scoring criteria for gastric cancer. FISH test was performed on the IHC score 2+ and 3+ cases and the results were correlated with clinicopathological findings.@*Results@#In total of 123 cases of gallbladder adenocarcinomas, HER2 amplification detection rate was 22.0%(27/123). Among 27 cases with HER2 gene amplification, 5 cases were IHC 2+ (5/12) and 22 cases were IHC 3+ (91.7%, 22/24), and the concordance rates between IHC and FISH were 41.7%and 91.7% respectively. The heterogeneity of HER2 expression was observed in 3 cases with complete strong cell membrane staining but the number of stained cells of<10%.Among them, 1 case showed HER2 gene amplification. The difference of HER2 gene amplification in well, moderately and lowly differentiated tumors has statistical significance(χ2=24.4, P<0.01), and its detection rate was related to the degree of tumor differentiation (C=0.45).@*Conclusions@#About 20% gallbladder adenocarcinomas have HER2 positivity, providing the targeted therapy implicationfor these patients.IHC HER2 scoring system for gastric carcinoma is suitable for gallbladder carcinoma. However, the cases with complete strong membrane staining but in <10% tumor cells should be included in the 2+ score IHC group.
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Purpose To explore the correlation between quantitative parameters from intravoxel incoherent motion (IVIM) with prognostic factors of rectal adenocarcinoma.Materials and Methods Eighty-six patients with rectal adenocarcinoma who were underwent surgery without neoadjuvant therapy in our hospital between September 2015 and July 2016 were selected in this retrospective study.The image data included multiple b-values diffusion weighted imaging (DWI) examination and the corresponding D,D* and f values of the lesions.Relationships between the quantitative parameters and tumor pathology indexes including histological differentiation grade,tumor T/N stage,lymphangiovascular invasion state,the expression level of epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor-2 (Her-2) were assessed.Results The average D values of different differentiation degree (high,middle and low) of rectal adenocarcinoma were (0.541±0.093)×10 3mm2/s,(0.490±0.156)×10-3mm2/s and (0.342 ± 0.147)× 10-3 mm2/s,and the difference was statistically significant (P＜0.05).TheD values were significantly different between the lymphangiovascular invasion and non invasion state [(0.511 ±0.154)× 10-3 mm2/s vs (0.387±0.130)×10-3 mm2/s,P＜0.05)].However,there were no significant differences in the mean D,D* and f values among different tumor T/N stage (P＞0.05).The average f value of EGFR or Her-2 high expression group was higher than that of low expression group (0.379±0.076 vs 0.298±0.099,P＜0.01;0.356±0.097 vs 0.298±0.098,P＜0.05,respectively).Conclusion Quantitative parameters of IVIM in rectal adenocarci-noma can be used as noninvasive imaging biomarkers to predict the biologic behavior of tumor and the prognosis of the patients.
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Objective To investigate the expression differences of β‐catenin ,Her‐2/Neu and ki‐67 in different pathological features of gastric cancer and their role in the occurrence ,progression ,invasion and metastasis of gastric cancer invasion and metas‐tasis .Methods The expression of β‐catenin ,ki‐67 and Her‐2/Neu in 150 gastric cancer tissue samples(observation group) and 70 normal gastric mucosal samples were detected by adopting the immunohistochemistry method ,and the relationship between the ex‐pression of β‐catenin ,ki‐67 and Her‐2/Neu with the pathological features of gastric cancer was analyzed .Results Theβ‐catenin ,ki‐67 and Her‐2/Neu positive rate in the observation group was significantly higher than that in the control group (χ2 =30 .51 ,63 .74 , 11 .38 ,P<0 .01);the differentiation degree affected the expression of β‐catenin ,ki‐67 and Her‐2/Neu expression (χ2 =15 .82 ,8 .61 , 8 .11 ,P<0 .01);the lymph node metastasis affected the expression of ki‐67 and β‐catenin (χ2 = 6 .26 ,P< 0 .05;χ2 = 7 .36 ,P<0 .01);the invasion depth affected the expression of β‐catenin and ki‐67(χ2 =11 .34 ,P<0 .01);TMN affected the expression of ki‐67 and Her‐2/Neu(χ2 = 10 .85 ,14 .24 ,P< 0 .01);the β‐catenin and ki‐67 expression showed positive correlation .Conclusion β‐catenin ,ki‐67 and Her‐2/Neu may reflect the proliferation ,invasion and metastasis situation of tumor cells and their detection con‐duces to the judgment of prognosis .
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Purpose To explore the expressional differences of immunohistochemical indicators between the non-mass-like and mass-like breast cancers,and to identify the biological characteristics of non-mass-like breast cancer.Material and Methods Various immunohistochemical indicators (HER2,ER,PR,Ki-67) were analyzed in 19 cases non-mass-like cancer and 18 cases mass-like breast cancer retrospectively,and the expressional differences of the two groups were compared.Results 12 cases (63.2％) were diagnosed DCIS in the non-mass-like breast cancer group,but in the mass-like breast cancer group,the majority (12 cases,66.7％) were invasive cancer.HER2,ER,PR expression had no statistical difference between the two types (P＞0.05).But the Ki-67 positive rate expressed in non-mass-like breast cancer was lower significantly (P＜0.05).Conclusion The HE immunohistochemical characteristics of non-mass-like breast cancer are overlapped with that of mass-like breast cancer,but Ki-67 expression has significant difference between the two groups.There are some differences in biological characteristics of these two kinds of breast cancers.
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Background Worldwide, gastric cancer is the fourth cancer in incidence and the second most common cause of cancer death. Gastric cancer is asymptomatic in the early stages and very often diagnosed at advanced stages, determining a dismal prognosis. Expression of the HER2 gene has been identified in about 20% of gastric cancer cases, and its hyper-expression is associated with poor prognosis. Objective To investigate HER2 immunohistochemical expression in gastric adenocarcinoma and its relationship to the histological type and anatomic location. Methods A cross-sectional retrospective study analyzed the immunohistochemical expression of HER2 in a sample of 48 specimens of gastric cancer. Immunohistochemical analysis were performed using avidin-biotin-peroxidase method with C-erb B2 (clone EP1045Y), as a primary antibody (Biocare Medical, USA). Standardized gastric adenocarcinoma‘s HER2 expression criteria has been used in the analysis of samples. Results There were seven cases with reactivity for HER2. Five were of intestinal-type while two cases were of mixed-type in which the expression occurred in the intestinal component. It was identified a significant association of HER2 expression in the intestinal subtype of gastric adenocarcinoma (P=0.003). Regarding the anatomical site, HER2 was positive in only one (16.6%) of the six proximal cases and six (14.28%) of the 42 distal cases (P=0.88). Conclusion HER2 immunoexpression was identified in 14.6% of the samples, and the expression was significantly associated to Lauren’s intestinal subtype. .
Contexto O câncer gástrico ocupa o quarto lugar em incidência no mundo e é a segunda causa de óbito por neoplasia maligna. Por ser assintomático nas fases iniciais, na maioria das vezes, é diagnosticado em fases avançadas. A expressão do gene HER2 tem sido identificada em cerca de 20% dos casos de câncer gástrico e, sua hiper-expressão está associada a um pior prognóstico nestes pacientes. Objetivo Investigar a expressão imunoistoquímica do HER2 em espécimes de adenocarcinoma gástrico e sua relação com a classificação histológica e localização anatômica. Métodos Estudo transversal, retrospectivo, no qual foi analisada a expressão imunoistoquímica para o HER2, em uma amostra de 48 espécimes de câncer gástrico, através da técnica de imunoistoquímica, pelo método avidina-biotina-peroxidase utilizando anticorpo primário C-erb B2, clone EP1045Y (Biocare Medical, USA). Resultados Foram encontrados sete casos reativos para o HER2; destes, cinco eram casos de adenocarcinoma do tipo intestinal e dois eram casos do tipo misto, porém, nestes, a expressão ocorreu no componente intestinal, o que determinou uma associação significante da expressão de HER2 com o componente intestinal do adenocarcinoma gástrico (P=0,003). Em relação ao local anatômico, HER2 foi reativo em apenas um (16,6%) de seis casos proximais e seis (14,28%) dos 42 casos distais (P=0,88). Conclusão A expressão de HER2 ocorreu em 14,6% da amostra, associada significativamente ao subtipo intestinal de Lauren. .
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Aged , Female , Humans , Male , Middle Aged , Adenocarcinoma/metabolism , /analysis , Stomach Neoplasms/metabolism , Adenocarcinoma/pathology , Cross-Sectional Studies , Immunohistochemistry , Neoplasm Staging , Retrospective Studies , Stomach Neoplasms/pathologyABSTRACT
PURPOSE: To examine the expression of AKT and PTEN in a series of HER2-positive primary invasive breast tumors using immunohistochemistry, and to associate these expression profiles with classic pathologic features such as tumor grade, hormone receptor expression, lymphatic vascular invasion, and proliferation. METHODS: A total of 104 HER2-positive breast carcinoma specimens were prepared in tissue microarrays blocks for immunohistochemical detection of PTEN and phosphorylated AKT (pAKT). Original histologic sections were reviewed to assess pathological features, including HER2 status and Ki-67 index values. The associations between categorical and numeric variables were identified using Pearson's chi-square test and the Mann-Whitney, respectively. RESULTS: Co-expression of pAKT and PTEN was presented in 59 (56.7%) cases. Reduced levels of PTEN expression were detected in 20 (19.2%) cases, and these 20 tumors had a lower Ki-67 index value. In contrast, tumors positive for pAKT expression [71 (68.3%)] were associated with a higher Ki-67 index value. CONCLUSION: A role for AKT in the proliferation of HER2-positive breast cancers was confirmed. However, immunohistochemical detection of PTEN expression did not correlate with an inhibition of cellular proliferation or control of AKT phosphorylation, suggesting other pathways in these mechanisms of control. .
OBJETIVOS: Avaliar a expressão imuno-histoquímica de AKT e PTEN em uma série de carcinomas mamários invasivos HER2-positivos, e associar seus padrões de expressão com variáveis anatomopatológicas clássicas, como grau histológico, expressão de receptores hormonais, embolização vascular linfática e atividade proliferativa. MÉTODOS: Um total de 104 amostras de carcinomas mamários invasivos HER2-positivos foram preparadas em blocos de microarranjos de tecido para detecção imuno-histoquímica de PTEN e AKT fosforilada (pAKT). Cortes histológicos originais foram revistos para avaliação das características anatomopatológicas, incluindo o estado do HER2 e a avaliação da expressão de Ki-67. As associações entre as variáveis categóricas e as numéricas foram feitas com o uso dos testes do chi-quadrado de Pearson e Mann-Whitney, respectivamente. RESULTADOS: Co-expressão de pAKT e PTEN foi identificada em 59 (56,7%) casos. Expressão reduzida de PTEN foi detectada em 20 (19,2%) casos, e esses 20 tumores mostraram menores valores de Ki-67. Por outro lado, tumores positivos para pAKT [71 (68,3%)] apresentaram células positivas para valores mais altos de Ki-67. CONCLUSÕES: O papel de AKT na proliferação de carcinomas mamários HER-2 positiva foi confirmada. Entretanto, a detecção imuno-histoquímica de PTEN não se correlacionou com inibição da proliferação celular ou controle da fosforilação de AKT, sugerindo outras vias nesses mecanismos de controle. .
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Adult , Aged , Aged, 80 and over , Female , Humans , Middle Aged , Breast Neoplasms/genetics , Gene Expression Regulation, Neoplastic , /genetics , Oncogene Protein v-akt/physiology , PTEN Phosphohydrolase/geneticsABSTRACT
Objective To investigate the relationship between expression of Her-2 gene and the transfer number of axillary lymph node and its influence on prognosis.Methods A total of 351 cases with primary breast cancer from January 2008 to January 2011 were selected.The expression of Her-2 gene was detected by immunohistochemical method,and analyzed the relationship between it and the transfer number of axillary lymph node and its influence on prognosis.Results The expression of Her-2-,+,++ had no correlation with the transfer number of axillary lymph node (x2 =3.757,1.650,2.379,P ＞ 0.05),while the expression of Her-2 +++ had correlation with the transfer number of axillary lymph node (x2 =8.681,P ＜ 0.05).The 2 years survival rates in the expression of Her-2-,+,++,+++ were 77.01％ (201/261),85.00％ (34/40),29.17％(7/24),1 1.54％ (3/26),and which in the expression of Her-2--+ was significantly higher than that in the expression of Her-2 ++-+++ (x2 =61.605,P ＜ 0.01).The transfer number of axillary lymph node was 0 and 1-3,the 2 years survival rate in the expression of Her-2--+ was significantly higher than that in the expression of Her-2 ++-+++,and there was significant difference (x2 =61.605,14.747,P ＜ 0.05).The transfer number of axillary lymph node was 4-9 and ≥ 10,there was no significant difference in the 2 years survival rate between the expression of Her-2--+ and Her-2 ++-+++ (x2 =3.691,3.482,P ＞ 0.05).Conclusions The expression of Her-2-,+,++ has no correlation with axillary lymph node metastasis,and the 2 years survival rate in the expression of Her-2--+ is higher than that in the expression of Her-2 ++-+++,while Her-2-has no difference with Her-2 + in prognosis.While the transfer number of axillary lymph node ≤ 3,the expression of Her-2 gene may be an important prognostic factor.
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Over-expression of human epidermal growth factor receptor 2 (HER-2) protein is available in 20% to 25% of patients with breast cancer, and it is associated with serious aggressiveness, high recurrence rate, and increased mortality of cancer. Trastuzumab, a humanized antibody against HER-2, has shown high efficacy in breast cancer through multiple mechanisms. Currently, trastuzumab is used in adjuvant therapy for breast cancer or in metastatic settings. Trials of trastuzumab in combination with chemotherapy suggest that patients with HER-2-positive breast cancer also may benefit from this neoadjuvant chemotherapy. This article reviews the efficacy and adverse effects of trastuzumab in neoadjuvant chemotherapy for breast cancer.
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Objective To analyze and compare the fluorescence in situ hybridization(FISH) and immunohistochemical(IHC) for detecting HER-2 gene amplification and protein expression in breast cancer tissues .Methods 110 cases of breast cancer from Janu-ary 2008 to May 2012 receiving the modified radical mastectomy were selected .The resected breast cancer tissue was detected by FISH and IHC and the detected results were performed the comparative analysis .Results Among 110 cases of breast cancer tissue , 25 cases(22 .73% ) were the HER-2 protein expression(+ + + ) ,44 cases(40 .00% ) were(+ + ) ,26 cases(23 .64% ) were(+ ) and 15 cases(13 .64% ) were(-) .Among 110 cases ,the gene amplification was in 28 cases(25 .45% ) and no gene amplification was in 82 cases(74 .55% ) .The positive(+ + + ) of the IHC detection was coincident with that of FISH ,and the negative(+ /-) of the IHC detection was also coincident with that of FISH ,there was statistical difference between the suspicious positive of the IHC de-tection and the results of FISH (P<0 .05) .But the total coincidence of the IHC detection results and FISH test results was 89 .29%(25/28) ,and the two detection methods had the positive correlation (χ2 =84 .89 ,P<0 .01) .Conclusion The positive and negative expression of the IHC detection has better consistency with that of the FISH detection .However ,the coincidence of the IHC suspi-cious positive expression and the FISH results is poor ,indicating that the suspicious positive sample of the IHC detection needs to be detected by the FISH detection .
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Objetivos: Identificar a prevalência de HER-2 e do fator de crescimento do endotélio vascular (VEGF) em biópsias de osteossarcoma e correlacioná-los com possíveis fatores de prognóstico. Métodos: estudo retrospectivo realizado no Hospital de Câncer de Barretos-SP incluindo 27 biópsias de osteossarcoma imuno-histoquimicamente coradas para VEGF e HER-2. Características clínico-patológicas foram coletadas dos prontuários médicos dos pacientes para correlação com marcadores. Resultados: em 27 biópsias, quatro foram superexpressas para VEGF e três para HER-2. Dois terços dos pacientes eram não metastáticos. Quase todos pacientes com VEGF superexpresso apresentaram metástases. A superexpressão para HER-2 apresentou relação inversa à presença de metástases. Não houve associação significativa entre os marcadores e o prognóstico. Conclusão: identificamos baixa prevalência de VEGF e HER-2 na amostra. Não houve associação significativa entre superexpressão dos marcadores e características clínico-patológicas. A ampliação da amostra e do tempo de seguimento, além do emprego de novas técnicas laboratoriais pode determinar a real expressão de VEGF e HER-2 e seu papel em osteossarcomas. Nível de Evidência III, Estudo de Caso-controle.
Objectives: To identify the prevalence of erbB-2 and vascular endothelial growth factor (VEGF) in osteosarcoma biopsies and to correlate them with possible prognosis factors. Methods: retrospective study conducted at the Hospital do Câncer de Barretos-SP including 27 osteosarcoma biopsies immunohistochemically stained for VEGF and erbB-2. The pathological characteristics were collected from medical records of patients to correlate with markers. Results: In 27 biopsies, four overexpressed VEGF and three overexpressed erbB-2. Two thirds of patients had no metastases. Almost all patients with overexpression of VEGF showed metastases. Overexpression of erbB-2 was inversely related to the presence of metastases. There was no significant association between markers and prognosis. Conclusion: We identified a low prevalence of erbB-2 and VEGF in the sample. There was no significant association between overexpression of markers and pathological features. A larger sample and a longer follow-up, in addition to using new laboratory techniques can determine the real expression of VEGF and erbB-2 and its role in osteosarcoma. Level of Evidence III, Case-Control Study.
Subject(s)
Humans , Male , Female , Child, Preschool , Child , Adolescent , Young Adult , Immunohistochemistry , Bone Neoplasms/immunology , Oncogenes , Vascular Endothelial Growth Factor A , Biopsy , Medical RecordsABSTRACT
Introdução: A hipótese de que os efeitos do alumínio em células humanas podem ter implicações clínicas tem sido levantada há algum tempo, especialmente no que concerne ao câncer de mama. As evidências laboratoriais mostrando altos níveis de alumínio nos tecidos da mama e os efeitos biológicos conhecidos sobre esse metal não são suficientes para estabelecer uma relação causal entre a exposição ao alumínio e o risco aumentando para o desenvolvimento do câncer de mama. O objetivo deste estudo foi estabelecer a concentração de alumínio nas áreas centrais e periféricas de tumores de mama, assim como na área glandular normal da mama e correlacionar esses achados com a instabilidade dos genes ERBB2, C-MYC e CCND1 e a aneuploidia dos cromossomos que contêm estes genes. Métodos: Para este estudo foram incluídas 176 mulheres com diagnóstico de carcinoma invasor de mama, com tumores maiores de 1cm3, sem quimioterapia neoadjuvante, operadas enter 2008 e 2010 no Hospital da Mulher Prof. Dr. José Aristodemo Pinotti - Centro de Atenção Integral à Saúde da Mulher (CAISM) - UNICAMP. Para a análise da concentração de alumínio intracelular, amostras de 150 pacientes foram consideradas viáveis; para a análise da instabilidade genômica em função da concentração de alumínio, 118 amostras foram consideradas viáveis, definindo o espaço amostral de cada um dos artigos apresentados. As amostras das áreas centrais e periféricas dos tumores de mama e das áreas glandulares normais da mama foram obtidas. A quantificação do alumínio contido nos tecidos da mama foi feita através da técnica de Espectrometria de Absorção Atômica em Forno de Grafite (GFAAS). Uma lâmina de Tissue Microarray (TMA), contendo as amostras de tumor e tecido normal foi utilizado para a realização da técnica de FISH para acessar o status dos genes ERBB2, C-MYC e CCND1 e dos centrômeros dos seus respectivos cromossomos 17, 8 e 11. Os dados clínico-patológicos foram obtidos dos prontuários de pacientes...
Introduction: It has long been hypothesized if the effects of aluminum on human cells may have clinical implications, especially regarding to breast cancer. The current laboratorial evidence showing higher levels of aluminum in breast tissues and the known biological effects of this metal, are not sufficient to establish a causal relationship between aluminum exposure and increased risk of developing breast cancer. The objective of this study was to establish the aluminum concentration in the central and peripheral areas of breast tumors as well as in normal glandular area of the breast and to correlate these findings with the instability of ERBB2, C-MYC and CCND1, and aneuploidy of chromosomes harboring these genes. Methods: This study included 176 women diagnosed with invasive breast carcinoma with tumors larger than 1cm3 without neoadjuvant chemotherapy, operated between 2008 and 2010 at the Women's Hospital Professor. Dr. José Aristodemo Pinotti - Centro de Atenção Integral à Saúde da Mulher (CAISM) - UNICAMP. To analyze the intracellular concentration of aluminum, samples from 150 patients were considered viable; for the analysis of genomic instability as a function of the concentration of aluminum, 118 samples were considered viable. These figures define the sample of each of the two articles that this PhD thesis comprises. Evaluation of tissue aluminum content was carried out using Graphite Furnace Atomic Absorption Spectrometry (GFAAS). A TMA slide containing the tumor and normal samples was used in FISH assays to assess ERBB2, C-MYC and CCND1 and the respective chromosomes 17, 8 and 11 centromeres status. Clinicopathological data were obtained from patients' records. Results: The average aluminum content found in breast was 1.88 mg/kg in the central tumor areas, 2.10 mg/ kg in the peripheral tumor areas and 1.68 mg/ kg in the normal tissue areas...
Subject(s)
Humans , Female , Aluminum/adverse effects , Breast Neoplasms , Genomic Instability , Cyclin D1 , Genes, mycABSTRACT
Objective Based on real-time PCR technique and ring primers,to establish a simple,accurate,cost-effective and easily standardized quantitative assay for quantification of HER2 mRNA,and apply to provide medication guidance for clinical tumor personalized molecular targeted therapy.Methods Screening reference gene which was stable expression in breast cancer,and optimizing the PCR reaction system.Then a real-time PCR with Eva Green for quantification of the mRNA expression levels of HER2 gene was developed.The specificity,sensitivity and reproducibility of the method were evaluated 87 specimens including 55 liquid nitrogen-frozen breast cancer tissues and 32 normal tissues were detected by the real-time quantitative reverse transcription (FQ RT)-PCR and immunohistochemistry(IHC).Results The standard curve of the method indicated a good linear relationship between the Ct value and the template concentration with the correlation coefficient being 0.997.The linear range of the system was from 101 to 106 copies/μl and the lower detection limit was 101 copies/μl.It had a high sensitivity and good specificity.The inter-assay coefficients of variation of HER and RPL37A genes were (5.93 ± 0.57)％ and (5.11 ± 0.59)％,(2.49 ±0.81)％ and (2.98 ±0.97)％ respectively.The intra-assay coefficients of variation were (5.76 ±0.58)％and (7.71 ±0.61)％,(3.75 ±0.76)％ and (4.40 ±0.96)％ respectively.Using the optimized FQ RTPCR system,HER2 gene of 87 specimens was quantificated.The sensitivity of the assay was 96.36％ (53/55),the specificity was 78.13％ (25/32),the positive predictive value was 88.33％ (53/60),the negative predictive value was 92.59％ (25/27),and the total coincidence rate between FQ RT-PCR and IHC was 89.66％ (78/87).The correlation of the results between the FQ RT-PCR and IHC was good (Kappa =0.770,P ＞ 0.05).Conclusions The method can quantify the mRNA expression levels of HER2 gene rapidly and cost-effictively with high sensitivity and specificity.It can be applied to clinical molecular diagnosis with attractive prospect.