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Objective
To explore the relationship between TTF-1 and EGFR mutations in lung adenocarcinoma tissues to guide clinical treatment timely and effectively.Materials and Methods
we collected 664 tissue samples from patients with histologically confirmed lung adenocarcinoma from May 2010 to April 2013. All tumor tissues were collected prior to administering therapy. TTF-1 was detected byimmunohistochemistry and EGFR mutations by DNA direct sequencing. Finally, the correlation between TTF-1 expression and the presence of EGFR mutations was analyzed using χ2 test or Fisher’s exact test with SPSS software version 18.0.Results
Of the 664 lung adenocarcinoma tissue samples, 18 were partially positive for TTF-1 (+−), and 636 were positive for TTF-1 (+) resulting in a total positive rate of 98.49% (+,+−)(including partial positive). In only 10 cases was the TTF-1 negative (−); the negative rate was 1.51%. There were 402 cases without an EGFR mutation and 262 cases with EGFR mutations; the rate of mutations was 39.46%. The location of the EGFR mutation was exon 19 for 121 cases resulting in a mutation rate in exon 19 of 18.22%. The location of the EGFR mutation was exon 21 for 141 cases resulting in a mutation rate in exon 21 of 21.23%. Exon 18 and 20 detected by DNA direct sequencing no mutations.A Fisher’s exact test was used to determine the correlation between EGFR mutations and TTF-1 expression.for the whole, TTF-1 positive expression(including partial positive) has correlation with EGFR mutations (p<0.001),especially for Exon 21 expression,the correlation is significant (p = 0.008).Conclusion
In lung adenocarcinomas, positive and partial positive TTF-1 expression has a significant positive correlation with EGFR mutations(exon 19 and 21). In clinical practice, TTF-1 expression combine with EGFR mutations, especially exon 21 mutation can guide clinical treatment timely for lung adenocarcinomas. 相似文献3.
Katelin R Haynes Allison R Pettit Ran Duan Hsu-Wen Tseng Tibor T Glant Matthew A Brown Gethin P Thomas 《Arthritis research & therapy》2012,14(6):R253
Introduction
Ankylosing spondylitis (AS) is unique in its pathology where inflammation commences at the entheses before progressing to an osteoproliferative phenotype generating excessive bone formation that can result in joint fusion. The underlying mechanisms of this progression are poorly understood. Recent work has suggested that changes in Wnt signalling, a key bone regulatory pathway, may contribute to joint ankylosis in AS. Using the proteoglycan-induced spondylitis (PGISp) mouse model which displays spondylitis and eventual joint fusion following an initial inflammatory stimulus, we have characterised the structural and molecular changes that underlie disease progression.Methods
PGISp mice were characterised 12 weeks after initiation of inflammation using histology, immunohistochemistry (IHC) and expression profiling.Results
Inflammation initiated at the periphery of the intervertebral discs progressing to disc destruction followed by massively excessive cartilage and bone matrix formation, as demonstrated by toluidine blue staining and IHC for collagen type I and osteocalcin, leading to syndesmophyte formation. Expression levels of DKK1 and SOST, Wnt signalling inhibitors highly expressed in joints, were reduced by 49% and 63% respectively in the spine PGISp compared with control mice (P < 0.05) with SOST inhibition confirmed by IHC. Microarray profiling showed genes involved in inflammation and immune-regulation were altered. Further, a number of genes specifically involved in bone regulation including other members of the Wnt pathway were also dysregulated.Conclusions
This study implicates the Wnt pathway as a likely mediator of the mechanism by which inflammation induces bony ankylosis in spondyloarthritis, raising the potential that therapies targeting this pathway may be effective in preventing this process. 相似文献4.
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Chantal C. H. J. Kuijpers Cathy B. Moelans Henk-Jan van Slooten Anja Horstman John W. J. Hinrichs Shaimaa Al-Janabi Paul J. van Diest Mehdi Jiwa 《PloS one》2013,8(12)
Background
HER-2 is a prognostic and predictive marker, but as yet no technique is perfectly able to identify patients likely to benefit from HER-2 targeted therapies. We aimed to prospectively assess the added value of first-line co-testing by IHC, and multiplex ligation-dependent probe amplification (MLPA) and chromogenic in situ hybridization (CISH).Methods
As local validation, HER-2 MLPA and CISH were compared in 99 breast cancers. Next, we reviewed 937 invasive breast cancers, from 4 Dutch pathology laboratories, that were prospectively assessed for HER-2 by IHC and MLPA (and CISH in selected cases).Results
The validation study demonstrated 100% concordance between CISH and MLPA, if both methods were assessable and conclusive (81.8% of cases). Significant variation regarding percentages IHC 0/1+ and 2+ cases was observed between the laboratories (p<0.0001). Overall concordance between IHC and MLPA/CISH was 98.1% (575/586) (Kappa = 0.94). Of the IHC 3+ cases, 6.7% failed to reveal gene amplification, whereas 0.8% of the IHC 0/1+ cases demonstrated gene amplification. Results remained discordant after retrospective review in 3/11 discordant cases. In the remaining 8 cases the original IHC score was incorrect or adapted after repeated IHC staining.Conclusions
MLPA is a low-cost and quantitative high-throughput technique with near perfect concordance with CISH. The use of MLPA in routinely co-testing all breast cancers may reduce HER-2 testing variation between laboratories, may serve as quality control for IHC, will reveal IHC 0/1+ patients with gene amplification, likely responsive to trastuzumab, and identify IHC 3+ cases without gene amplification that may respond less well. 相似文献6.
Eoghan de Barra Susanne H. Hodgson Katie J. Ewer Carly M. Bliss Kerrie Hennigan Ann Collins Eleanor Berrie Alison M. Lawrie Sarah C. Gilbert Alfredo Nicosia Samuel J. McConkey Adrian V. S. Hill 《PloS one》2014,9(12)
Background
Plasmodium falciparum (P. falciparum) malaria remains a significant cause of mortality and morbidity throughout the world. Development of an effective vaccine would be a key intervention to reduce the considerable social and economic impact of malaria.Methodology
We conducted a Phase Ia, non-randomized, clinical trial in 24 healthy, malaria-naïve adults of the chimpanzee adenovirus 63 (ChAd63) and modified vaccinia virus Ankara (MVA) replication-deficient viral vectored vaccines encoding the circumsporozoite protein (CS) of P. falciparum.Results
ChAd63-MVA CS administered in a heterologous prime-boost regime was shown to be safe and immunogenic, inducing high-level T cell responses to CS. With a priming ChAd63 CS dose of 5×109 vp responses peaked at a mean of 1947 SFC/million PBMC (median 1524) measured by ELIspot 7 days after the MVA boost and showed a mixed CD4+/CD8+ phenotype. With a higher priming dose of ChAd63 CS dose 5×1010 vp T cell responses did not increase (mean 1659 SFC/million PBMC, median 1049). Serum IgG responses to CS were modest and peaked at day 14 post ChAd63 CS (median antibody concentration for all groups at day 14 of 1.3 µg/ml (range 0–11.9), but persisted throughout late follow-up (day 140 median antibody concentration groups 1B & 2B 0.9 µg/ml (range 0–4.7).Conclusions
ChAd63-MVA is a safe and highly immunogenic delivery platform for the CS antigen in humans which warrants efficacy testing.Trial Registration
ClinicalTrials.gov NCT01450280相似文献7.
Yeong-Shiau Pu Chao-Yuan Huang Jyue-Yu Chen Wang-Yi Kang Ying-Chu Lin Yu-Shiang Shiu Shu-Ju Chuang Hong-Jeng Yu Ming-Kuen Lai Yu-Chieh Tsai Wen-Jeng Wu Tzyh-Chyuan Hour 《Journal of biomedical science》2012,19(1):39
Background
Metastatic renal cell carcinoma (RCC) is highly resistant to systemic chemotherapy. Unfortunately, nearly all patients die of the metastatic and chemoresistant RCC. Recent studies have shown the atypical PKCζ is an important regulator of tumorigenesis. However, the correlation between PKCζ expression and the clinical outcome in RCC patients is unclear. We examined the level of PKCζ expression in human RCC.Methods
PKCζ mRNA and protein expressions were examined by real-time polymerase chain reaction (PCR) and immunohistochemistry (IHC) respectively in RCC tissues of 144 patients. Cellular cytotoxicity and proliferation were assessed by MTT.Results
PKCζ expression was significantly higher in normal than in cancerous tissues (P < 0.0001) by real-time PCR and IHC. Similarly, PKCζ expression was down-regulated in four renal cancer cell lines compared to immortalized benign renal tubular cells. Interestingly, an increase of PKCζ expression was associated with the elevated tumor grade (P = 0.04), but no such association was found in TNM stage (P = 0.13). Tumors with higher PKCζ expression were associated with tumor size (P = 0.048). Expression of higher PKCζ found a poor survival in patients with high tumor grade. Down-regulation of PKCζ showed the significant chemoresistance in RCC cell lines. Inactivation of PKCζ expression enhanced cellular resistance to cisplatin and paclitaxel, and proliferation in HK-2 cells by specific PKCζ siRNA and inhibitor.Conclusions
PKCζ expression was associated with tumorigenesis and chemoresistance in RCC. 相似文献8.
Huan-Xin Lin Hui-Juan Qiu Fei Zeng Hui-Lan Rao Guo-Fen Yang Hsiang-Fu Kung Xiao-Feng Zhu Yi-Xin Zeng Mu-Yan Cai Dan Xie 《PloS one》2013,8(4)
Background
It has been suggested that autophagy-related Beclin 1 plays a critical role in the regulation of tumor development and/or progression, but its prognostic significance and relationship with Bcl-xL expression in ovarian carcinoma are unclear.Methodology/Principal Findings
In the present study, the methods of Western blotting and immunohistochemistry (IHC) were utilized to investigate the expression status of Beclin 1 and Bcl-xL in fresh ovarian tissues and paraffin-embedded epithelial ovarian tumor tissues. Decreased expression of Beclin 1 was examined by IHC in 8.3% of normal ovaries, in 15.4% of cystadenomas, in 20.0% of borderline tumors, and in 55.6% of ovarian carcinomas, respectively. In ovarian carcinomas, decreased expression of Beclin 1 was correlated closely with ascending histological grade, later pT/pN/pM status and/or advanced clinical stage (P<0.05). In univariate survival analysis, a highly significant association between low-expressed Beclin 1 and shortened patient survival was evaluated in ovarian carcinoma patients (P<0.01), and Beclin 1 expression was an independent prognostic factor as evidenced by multivariate analysis (P = 0.013). In addition, decreased expression of Beclin 1 was inversely correlated with altered expression of Bcl-xL in ovarian carcinoma cohort, and combined analysis further showed that the low Beclin 1/high Bcl-xL group had the lowest survival rate.Conclusions/Significance
Our findings suggest that Beclin 1 expression, as examined by IHC, could be served as an additional tool in identifying ovarian carcinoma patients at risk of tumor progression, and predicting patient survival in ovarian carcinomas with increased expression of Bcl-xL. 相似文献9.
Gloria B. Roldán Urgoiti Karla Gustafson Alexander C. Klimowicz Stephanie K. Petrillo Anthony M. Magliocco Corinne M. Doll 《PloS one》2014,9(10)
Background
In anal cancer studies, the detection frequency of high-risk HPV (human papillomavirus) is variable, depending on the method used. There are limited data reporting results of different HPV detection techniques in the same clinical series, and very few correlating results with clinical outcome.Objectives
To evaluate tumor expression of p16/HPV16 using three different methods, and to determine their association with clinical outcome in patients with anal canal squamous cell carcinomas (SCC).Design
This retrospective study included patients with anal canal SCC treated with definitive radiotherapy or chemoradiotherapy at a single institution between 1992 and 2005. Formalin-fixed paraffin–embedded tumor samples from 53 of the 89 (60%) patient pre-treatment biopsies were adequate for tissue microarray construction. HPV status was determined using: p16 expression by conventional immunohistochemistry (IHC) and quantitative IHC (AQUA), HPV genotype analysis by chromogenic in situ hybridization (CISH) and HPV linear array sub-typing. Expression status was correlated with clinical outcome.Results
80% (28/35) of patient tumors had high p16 expression using conventional IHC. HPV16 CISH was positive in 81% (34/42) of tumors, and 78% (28/36) of tumors were HPV subtype 16. HPV16 CISH correlated with p16 evaluated by conventional IHC (correlation coefficient 0.46; p = 0.01) and by p16 AQUA score (correlation coefficient 0.49; p = 0.001). A subset of cases (15%) had very high p16 quantitative IHC scores (>244) and were associated with a higher incidence of local or distant recurrence (p = 0.04).Conclusions
The vast majority (80%) of anal canal SCC in our series were positive for HPV16/p16, regardless of the testing method used. The exploratory analysis of automated quantitative IHC scoring was the only technique to define a subset of patients with a worse prognosis by p16 expression status on univariate analysis. Further exploration of the molecular mechanisms of treatment resistance in association with very high p16 expression is warranted. 相似文献10.
Javier Modrego Luis Azcona Naiara Martín-Palacios José J. Zamorano-León Antonio Segura Pablo Rodríguez Reddy Guerra Juan Tamargo Carlos Macaya Antonio J. López-Farré 《PloS one》2013,8(12)
Objective
To analyse if platelet responsiveness to aspirin (ASA) may be associated with a different ability of platelets to generate nitric oxide (NO).Patients/Methods
Platelets were obtained from 50 patients with stable coronary ischemia and were divided into ASA-sensitive (n = 26) and ASA-resistant (n = 24) using a platelet functionality test (PFA-100).Results
ASA-sensitive platelets tended to release more NO (determined as nitrite + nitrate) than ASA-resistant platelets but it did not reach statistical significance. Protein expression of nitric oxide synthase 3 (NOS3) was higher in ASA-sensitive than in ASA-resistant platelets but there were no differences in the platelet expression of nitric oxide synthase 2 (NOS2) isoform. The highest NOS3 expression in ASA-sensitive platelets was independent of the presence of T-to-C mutation at nucleotide position −786 (T−786→C) in the NOS3-coding gene. However, platelet content of phosphorylated NOS3 at Serine (Ser)1177, an active form of NOS3, was higher in ASA-sensitive than in ASA-resistant platelets. The level of platelet NOS3 Ser1177 phosphorylation was positively associated with the closure time in the PFA-100 test. In vitro, collagen failed to stimulate the aggregation of ASA-sensitive platelets, determined by lumiaggregometry, and it was associated with a significant increase (p = 0.018) of NOS3 phosphorylation at Ser1177. On the contrary, collagen stimulated the aggregation of ASA-resistant platelets but did not significantly modify the platelet content of phosphorylated NOS3 Ser1177. During collagen stimulation the release of NO from ASA-sensitive platelets was significantly enhanced but it was not modified in ASA-resistant platelets.Conclusions
Functional platelet responsiveness to ASA was associated with the platelet content of phosphorylated NOS3 at Ser1177. 相似文献11.
Introduction
Breast cancer is the most common malignancy affecting females worldwide but conventional risk factors are able to explain only a small proportion of these cases. A possible viral etiology for breast cancer has been proposed and Epstein-Barr Virus (EBV) is a widely researched candidate virus. The aim of the present study, first one of its kind from India, was to determine if there is a greater association of EBV infection with breast cancer patients as compared to patients with benign breast diseases.Methods
We looked for expression of Epstein-Barr Virus Nuclear Antigen-1 (EBNA-1) in breast cancer tissue specimens by employing immunohistochemistry (IHC). We also measured levels of anti-EBNA-1 Immunoglobulin (IgG) antibodies in stored sera of these patients using commercial Enzyme linked Immunosorbent Assay (ELISA) kit. Patients with benign breast diseases were used as a comparison group for both immunohistochemical and serological analysis.Results
58 cases of malignant breast disease and 63 of benign breast disease (controls) were included in the study. Using manufacturer determined cut-off of 3 IU/ml, 50/55 tested (90.9%) cases and 27/33 tested (81.8%) controls were seropositive for anti-EBNA-1 IgG. Mean antibody levels were significantly higher for cases (54.22 IU/ml) as compared to controls (18.68 IU/ml). IHC for EBNA-1 was positive in 28/51 cases (54.9%). No IHC positivity was noted in the tested 30 controls. Our results show that EBNA-1 expression is seen in a significant proportion of breast cancer tissue specimens from rural India and as compared to patients with benign breast diseases these patients also have a higher immunological response against EBNA-1. 相似文献12.
Background
Cyclooxygenase-2 (COX-2) is believed to be an important enzyme in the pathogenesis of colorectal cancer (CRC). Correlations between the expression of COX-2 with tumor growth and distant metastasis have become an issue; thus, attention has been paid to COX-2 as a prognostic factor. Various studies examined the relationship between COX-2 immunohistochemistry (IHC) overexpression with the clinical outcome in patients with colorectal cancer, but yielded conflicting results. The prognostic significance of COX-2 overexpression in colorectal cancer remains controversial.Methods
Electronic databases updated to October 2012 were searched to find relevant studies. A meta-analysis was conducted with eligible studies which quantitatively evaluated the relationship between COX-2 overexpression and survival of patients with colorectal cancer. Survival data were aggregated and quantitatively analyzed.Results
We performed a meta-analysis of 23 studies (n = 4567 patients) that evaluated the correlation between COX-2 overexpression detected by IHC and survival in patients with colorectal cancer. Combined hazard ratios suggested that COX-2 overexpression had an unfavorable impact on overall survival (OS) (HR [hazard ratio] = 1.193, 95% CI [confidence interval]: 1.02 ∼ 1.37), but not disease free survival (DFS) (HR = 1.25, 95% CI: 0.99 ∼ 1.50) in patients with colorectal cancer.Conclusions
Cox-2 overexpression in colorectal cancer detected by IHC appears to have slightly worse overall survival. However, the prognostic value of COX-2 on survival in colorectal cancer still needs further large-scale prospective trials to be clarified. 相似文献13.
Lars Knudsen Elena N. Atochina-Vasserman Chang-Jiang Guo Pamela A. Scott Beat Haenni Michael F. Beers Matthias Ochs Andrew J. Gow 《PloS one》2014,9(1)
Rationale
Surfactant protein D (SP-D) has important immuno-modulatory properties. The absence of SP-D results in an inducible NO synthase (iNOS, coded by NOS2 gene) related chronic inflammation, development of emphysema-like pathophysiology and alterations of surfactant homeostasis.Objective
In order to test the hypothesis that SP-D deficiency related abnormalities in pulmonary structure and function are a consequence of iNOS induced inflammation, we generated SP-D and iNOS double knockout mice (DiNOS).Methods
Structural data obtained by design-based stereology to quantify the emphysema-like phenotype and disturbances of the intracellular surfactant were correlated to invasive pulmonary function tests and inflammatory markers including activation markers of alveolar macrophages and compared to SP-D (Sftpd−/−) and iNOS single knockout mice (NOS2−/−) as well as wild type (WT) littermates.Measurements and Results
DiNOS mice had reduced inflammatory cells in BAL and BAL-derived alveolar macrophages showed an increased expression of markers of an alternative activation as well as reduced inflammation. As evidenced by increased alveolar numbers and surface area, emphysematous changes were attenuated in DiNOS while disturbances of the surfactant system remained virtually unchanged. Sftpd−/− demonstrated alterations of intrinsic mechanical properties of lung parenchyma as shown by reduced stiffness and resistance at its static limits, which could be corrected by additional ablation of NOS2 gene in DiNOS.Conclusion
iNOS related inflammation in the absence of SP-D is involved in the emphysematous remodeling leading to a loss of alveoli and associated alterations of elastic properties of lung parenchyma while disturbances of surfactant homeostasis are mediated by different mechanisms. 相似文献14.
Yun Lu Christopher Futtner Jason R. Rock Xia Xu Walter Whitworth Brigid L. M. Hogan Mark W. Onaitis 《PloS one》2010,5(6)
Background
SOX2 (Sry-box 2) is required to maintain a variety of stem cells, is overexpressed in some solid tumors, and is expressed in epithelial cells of the lung.Methodology/Principal Findings
We show that SOX2 is overexpressed in human squamous cell lung tumors and some adenocarcinomas. We have generated mouse models in which Sox2 is upregulated in epithelial cells of the lung during development and in the adult. In both cases, overexpression leads to extensive hyperplasia. In the terminal bronchioles, a trachea-like pseudostratified epithelium develops with p63-positive cells underlying columnar cells. Over 12–34 weeks, about half of the mice expressing the highest levels of Sox2 develop carcinoma. These tumors resemble adenocarcinoma but express the squamous marker, Trp63 (p63).Conclusions
These findings demonstrate that Sox2 overexpression both induces a proximal phenotype in the distal airways/alveoli and leads to cancer. 相似文献15.
Fen Zhu Weige Wang Yingyong Hou Jindong Shi Zilong Liu Deming He Chunxue Bai Shanqun Li Liyan Jiang 《PloS one》2014,9(4)
Introduction
Primary pulmonary mucoepidermoid carcinoma (PMEC) is an uncommon neoplasm with remarkable resemblance to mucoepidermoid carcinoma of the salivary glands. The latter has been shown to harbor t(11,19) resulting in MECT1-MAML2 fusion, which may be of diagnostic and prognostic values. However, the importance of such feature in PMEC has not been well studied.Methods
We detected MAML2 rearrangement using fluorescence in situ hybridization (FISH) in tissue samples from 42 cases of PMEC and 40 of adenosquamous carcinoma (ASC), and the expression of potential downstream targets of MECT1-MAML2, including HES1, FLT1 and NR4A2 with immunohistochemistry (IHC). The findings were then examined regarding the clinicopathological parameters and patient outcomes.Results
FISH analysis revealed MAML2 rearrangement in 50% of the PMEC cases, and such property was prominent in considerable younger patients (33 versus 60 years; p = 0.001) and restricted to cases of low and intermediate grades. IHC analysis showed that FLT1 and HES1 were expressed at lower level in MAML2 rearranged group than MAML2 non-rearranged group (p<0.001 and p = 0.023, respectively). Survival analysis showed significant correlation between MAML2 rearrangement and overall survival (p = 0.023) or disease-free survival (p = 0.027) as well as correlation between FLT1 and overall survival (p = 0.009).Conclusions
MAML2 rearrangement appears frequent in PMEC and specific with this tumor. Both the presence of MAML2 rearrangement and absence of FLT1 tend to confer a favorable clinical outcome. These findings suggest that molecular detection of MAML2 rearrangement combined with FLT1 may be of important clinical value for PMEC. 相似文献16.
Jakub Pazdrowski Pieńkowski Piotr Magdalena Kordylewska Anna Wegner Paweł Golusiński Wojciech Golusiński 《Reports of Practical Oncology and Radiotherapy》2010,15(3):60-63
Background
The exact assessment of a tonsil carcinoma''s size is often difficult because of the tumour''s submucosal extension and deep infiltration.Aim
The aim of the study is to assess the usefulness of intraoperative ultrasonography in tonsil cancer.Material
Twenty patients with carcinoma of the tonsil were included in the study (squamous cell carcinoma keratosis – 12, squamous cell carcinoma akeratosis – 6, diffuse large B cell lymphoma – 1, neoplasma malignum microcellulare – 1).Method
Transcutaneous, endoscopic, and intraoperative ultrasonography were performed using a linear 7.5 MHz probe.Results
The difference in the results was statistically significant between palpation examination and intraoperative ultrasonographic examination, between transcutaneous ultrasonographic examination and intraoperative ultrasonographic examination, and between endoscopic ultrasonographic examination and intraoperative ultrasonographic examination in tonsil tumours. Generally, tumour size assessed by intraoperative ultrasonography was more advanced than those assessed by other methods.Conclusions
Intraoperative ultrasonography is a safe, non-invasive method, which can be repeated at every stage of surgery. There were no contraindications or side effects. In all cases histological margins corresponded to sonographic margins. Intraoperative ultrasonography provides a quick and reliable orientation during resection of tonsil carcinoma. 相似文献17.
Background
Nonmelanoma skin cancer (NMSC),which includes squamous cell carcinoma (SCC) and basal cell carcinoma (BCC), is the most common form of cancer, and its incidence is increasing. Nonsteroidal anti-inflammatory drugs (NSAIDs) have been reported to be chemopreventive for NMSC. However, the results from published studies were controversial.Methods
We searched the PubMed and Embase databases for relevant studies. Moreover, relevant reviews regarding the use of NSAIDs for NMSC patients were examined for potential inclusive studies. To measure the effects of NSAIDs, the relative risk (RR) was analyzed.Results
A Total of 8 studies were included in our meta-analysis. We found that NSAIDs use was not associated with a reduced risk of SCC or BCC under the random effects model (pooled RR = 0.86, 95% CI, 0.73–1.02, P = 0.085; pooled RR = 0.94, 95% CI 0.85–1.04, P = 0.266; respectively).Conclusion
From the included studies, we found no statistically significant chemopreventive effect on NMSC of NSAIDs. This finding warrants more prospective studies evaluating the relationship between NSAIDs and NMSC. 相似文献18.
Introduction
HER2 status assessment became a mandatory test assay in breast cancer, giving prognostic and predictive information including eligibility for adjuvant anti-HER2 therapy. Precise and reliable assessment of HER2 status is therefore of utmost importance. In this study we analyzed breast cancer samples by a novel technology for concomitant detection of the HER2 protein and gene copy number.Methods
Tissue microarrays containing 589 invasive breast cancer samples were analyzed with a double immunohistochemistry (IHC) and silver labeled in situ hybridization (SISH) assay simultaneously detecting HER2 protein and gene copy number in the same tumor cells. This bright-field assay was analyzed using scores according to the modified ASCO guidelines and the results were correlated with patient prognosis.Results
Overall concordance rate between protein expression and the presence of gene amplification was 98%. Fifty-seven of 60 tumors (95%) with IHC score 3+, 6 of 10 tumors with IHC score 2+ (60%) and only 3 of 519 tumors (0.6%) with IHC score 0/1+ were amplified by SISH. Patients with gene amplification despite IHC score 0/1+ had a tendency for worse overall survival (p = 0.088, reaching nearly statistical significance) compared to IHC score 0/1+ without amplification. In contrast, there was no difference in overall survival in IHC score 3+/2+ tumors with and without gene amplification.Conclusions
The novel double IHC and SISH assay for HER2 is efficient in the identification of breast cancer with discordant HER2 protein and HER2 gene status, especially for the prognostically relevant groups of HER2 protein negative tumors with HER2 amplification and HER2 protein positive tumors without HER2 amplification. Breast cancer without HER2 amplification among IHC score 2+/3+ tumors (10% in our cohort) suggests that other mechanisms than gene amplification contribute to protein overexpression in these cells. 相似文献19.
20.
Lifeng Yan Wenhui Guo Shengmin Wu Jining Liu Shenghu Zhang Lili Shi Guixiang Ji Aihua Gu 《PloS one》2014,9(12)