Evaluation of serum HER2 extracellular domain in in metastatic gastric or gastroesophageal junction cancer: Correlation with HER2 status by immunohistochemistry and fluorescence in situ hybridization and clinicopathologic parameters.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 4107-4107
Author(s):  
Xin An ◽  
Shuqin Dai ◽  
Fang Wang ◽  
Qiong Shao ◽  
Cui Chen ◽  
...  
Keyword(s):  
In Situ Hybridization ◽  
Gastroesophageal Junction ◽  
Locally Advanced ◽  
Surrogate Marker ◽  
High Specificity ◽  
Extracellular Domain ◽  
High Serum ◽  
Clinicopathological Parameters ◽  
Her2 Status

4107 Background: To explore the association between serum human epidermal growth factor receptor-2 (HER2) extracellular domain (ECD) and tissue HER2 status, their relationship with clinicopathological parameters and impact on overall survival (OS) in metastatic gastric or gastro-oesophageal junction (GEJ) adenocarcinoma. Methods: A total of 219 histologically confirmed inoperable locally advanced, recurrent, or metastatic gastric or GEJ adenocarcinoma were included. Serum HER2 ECD was measured by chemiluminescent assay. Tissue HER2 status was accessed by fluorescent in situ hybridization (FISH) and immunohistochemistry (IHC) assay. Results: The median serum ECD level was 9.3 ng/ml (range 3.0 to >350). Tissue HER2 status was positive (IHC3+ or 2+ with FISH amplification) in 37 patients (16.9%) and negative in 182 patients (83.1%). Statistically significant associations were found between serum HER2 ECD level and HER2 status assessed by IHC and FISH. The ROC-analysis suggested the cutoff of 16.35 ng/ml (24 of 219 patients had HER2 ECD >16.35 ng/ml ) could produce a sensitivity of 51.4% and a specificity of 97.3% to predict tissue HER2 status. If the cutoff value was increaseed to 22 ng/ml, then all 12 patients with serum HER2 ECD >22 ng/ml were HER 2 positive in primary tumor, corresponding to a specificity of 100% and a sensitivity of 32.4%. High serum HER2 ECD levels were strongly associated with liver metastasis (P < 0.001), the intestinal histologic type (Lauren's classification) (P =0.003), large number of metastais (>2) (P=0.012) and increased LDH level (P < 0.001) . High serum HER2 ECD levels were more common in GEJ adenocarcinoma although the difference had no stastical significance. HER2 ECD levels did not show a significant impact on OS. Conclusions: A significant association was observed between serum HER2 ECD levels and tissue HER2 status in metastasis gastric or GEJ adenocarcinoma. The high specificity of serum HER2 ECD assay to predict tissue HER2 status suggests its potential use as a surrogate marker of the HER2 status in gastric cancer.

Iso-chromosome 12p Analysis by Fluorescent In-Situ Hybridization: An Academic Institutional Experience

2021 ◽  
Vol 156 (Supplement_1) ◽  
pp. S72-S72
Author(s):  
P P Patwardhan ◽  
S Satturwar ◽  
R Dhir ◽  
G M Quiroga-Garza
Keyword(s):  
In Situ Hybridization ◽  
Germ Cell ◽  
Fluorescent In Situ Hybridization ◽  
Clinical Presentation ◽  
Germ Cell Tumors ◽  
High Specificity ◽  
Testicular Germ Cell ◽  
Chromosome 12P ◽  
Institutional Experience

Abstract Introduction/Objective Chromosome 12 abnormalities like iso-chromosome 12p (i12p) and amplification of 12p are seen in majority (89%) of the primary and metastatic testicular germ cell tumors (TGCTs). i12p can be detected by karyotyping, fluorescent in-situ hybridization (FISH) or reverse transcriptase polymerase chain reaction. The aim of this study was to review i12p FISH data at our institution and assess the clinical utility. Methods/Case Report Laboratory information system was queried over a period of 15 years to search for cases where i12p FISH test was requested. FISH test was performed using TelVysion 12p telomeric probe and CEP 12 centromere probe on paraffin-embedded tissue or cell blocks. A ratio of 12ptel/CEP12 signal of 1.4 or greater was considered as positive. Patient demographics, clinical presentation, pathologic findings, and follow-up data were documented and correlated. Results (if a Case Study enter NA) Total 58 cases were identified with an age range of 14 to 76 years. Majority were male (M=52, F=6). Of these cases, 15 were testicular and 43 extra-testicular cases that included resection (n=35), biopsy (n=20) and cell-blocks (n=3). i12p was detected in 8 out of 15 testicular cases while i12p was detected in 16 out of the 43 extra-testicular cases. The extra- testicular cases included 17 retroperitoneal lesions, 8 lesions from the mediastinum, 6 lymph nodes from other sites and 12 miscellaneous lesions. Using pathology diagnosis with immunohistochemistry as gold standard, overall sensitivity was 60% and specificity was 86%. There were 3 false positive cases [Benign testicular parenchyma (n=1), suspicious for germ cell neoplasia in-situ (n=1) and undifferentiated epithelioid neoplasm (n=1)]. Conclusion Our results show that although the sensitivity was limited, FISH test for i12p demonstrated high specificity(86%) for diagnosis of primary or metastatic TGCTs. As an adjunct test, i12p FISH can help identify and further characterize a significant number of GCTs with unusual morphology or clinical presentation.

scholarly journals Detection of HER2 Amplification in Breast Carcinomas: Comparison of Multiplex Ligation-Dependent Probe Amplification (MLPA) and Fluorescence In Situ Hybridization (FISH) combined with Automated Spot Counting

2006 ◽  
Vol 28 (4) ◽  
pp. 151-159
Author(s):  
Elna Moerland ◽  
Rens L. H. P. M. van Hezik ◽  
Toine C. J. M. van der Aa ◽  
Mike W. P. M. van Beek ◽  
Adriaan J. C. van den Brule
Keyword(s):  
In Situ Hybridization ◽  
Fluorescence In Situ Hybridization ◽  
Gene Amplification ◽  
Her2 Status ◽  
Her2 Amplification ◽  
Breast Carcinomas ◽  
Her2 Gene ◽  
Her2 Gene Amplification ◽  
Dependent Probe

In this study the detection of HER2 gene amplification was evaluated using Fluorescence In Situ Hybridization (FISH; PathVysion) in comparison with Multiplex Ligation-dependent Probe Amplification (MLPA), a PCR based technique. These two methods were evaluated on a series of 46 formalin fixed paraffin embedded breast carcinomas, previously tested for protein overexpression by HercepTest (grouped into Hercep 1+, 2+ and 3+). HER2 gene amplification (ratio ≥ 2.0) by FISH was found in 9/10, 10/30 and 0/6 in IHC 3+, 2+ and 1+/0 cases, respectively. Digitalized automated spot counting performed with recently developed CW4000 CytoFISH software was 100% concordant with manual FISH scoring. Using MLPA 18/46 samples showed a clear HER2 amplification. Comparing MLPA and IHC showed the same results as for FISH and IHC. All but one FISH positive cases (18/19) were confirmed by MLPA for the presence of the gene amplification. The overall concordance of detection of Her2 gene amplification by FISH and MLPA was 98% (45/46). Furthermore, both the level of amplification and equivocal results correlated well between both methods. In conclusion, MLPA is a reliable and reproducible technique and can be used as an either alternative or additional test to determine HER2 status in breast carcinomas.

scholarly journals Consensus recommendations for risk stratification in multiple myeloma: report of the International Myeloma Workshop Consensus Panel 2

Blood ◽  
2011 ◽  
Vol 117 (18) ◽  
pp. 4696-4700 ◽  
Author(s):  
Nikhil C. Munshi ◽  
Kenneth C. Anderson ◽  
P. Leif Bergsagel ◽  
John Shaughnessy ◽  
Antonio Palumbo ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
In Situ Hybridization ◽  
High Risk ◽  
Risk Stratification ◽  
Fluorescence In Situ Hybridization ◽  
High Serum ◽  
Β2 Microglobulin ◽  
Poor Outcome ◽  
13Q Deletion

Abstract A panel of members of the 2009 International Myeloma Workshop developed guidelines for risk stratification in multiple myeloma. The purpose of risk stratification is not to decide time of therapy but to prognosticate. There is general consensus that risk stratification is applicable to newly diagnosed patients; however, some genetic abnormalities characteristic of poor outcome at diagnosis may suggest poor outcome if only detected at the time of relapse. Thus, in good-risk patients, it is necessary to evaluate for high-risk features at relapse. Although detection of any cytogenetic abnormality is considered to suggest higher-risk disease, the specific abnormalities considered as poor risk are cytogenetically detected chromosomal 13 or 13q deletion, t(4;14) and del17p, and detection by fluorescence in situ hybridization of t(4;14), t(14;16), and del17p. Detection of 13q deletion by fluorescence in situ hybridization only, in absence of other abnormalities, is not considered a high-risk feature. High serum β2-microglobulin level and International Staging System stages II and III, incorporating high β2-microglobulin and low albumin, are considered to predict higher risk disease. There was a consensus that the high-risk features will change in the future, with introduction of other new agents or possibly new combinations.

A phase Ib/II, multicenter, open-label, dose-escalation, and dose-expansion study evaluating trastuzumab deruxtecan (T-DXd, DS-8201) monotherapy and combinations in patients with HER2-overexpressing gastric cancer (DESTINY-Gastric03).

2021 ◽  
Vol 39 (3_suppl) ◽  
pp. TPS261-TPS261
Author(s):  
Yelena Y. Janjigian ◽  
Natasha Viglianti ◽  
Feng Liu ◽  
Ariadna Mendoza-Naranjo ◽  
Liz Croydon
Keyword(s):  
Gastric Cancer ◽  
Dose Escalation ◽  
Topoisomerase I ◽  
Gastroesophageal Junction ◽  
Objective Response ◽  
Locally Advanced ◽  
Metastatic Gastric Cancer ◽  
Her2 Status ◽  
Open Label ◽  
Phase 1B

TPS261 Background: For patients (pts) with HER2-overexpressing metastatic gastric cancer, trastuzumab + chemotherapy is a standard first-line option but provides only a modest overall survival (OS) benefit vs chemotherapy. T-DXd is an antibody-drug conjugate consisting of an anti-HER2 antibody, cleavable tetrapeptide-based linker, and a membrane-permeable topoisomerase I inhibitor payload. Results from a phase 1 trial showed promising antitumor activity (confirmed objective response rate [ORR], 43.2%) in pts with heavily pretreated HER2+ metastatic gastric cancer who received T-DXd (5.4 or 6.4 mg/kg; Shitara K, et al. Lancet Oncol. 2019;20:827-836). Here we describe the phase 1b/2 DESTINY-Gastric03 trial (NCT04379596) evaluating T-DXd monotherapy and combinations in pts with HER2-overexpressing gastric cancer. Methods: This is an open-label, multicenter, 2-part, phase 1b/2 study in pts with HER2-overexpressing (immunohistochemistry [IHC] 3+ or IHC 2+/in situ hybridization positive) locally advanced, unresectable or metastatic gastric or gastroesophageal junction cancer. In part 1 (dose escalation), pts who had received prior trastuzumab-containing therapy will be assigned to 1 of 5 arms: (1) T-DXd + 5-fluorouracil (5-FU); (2) T-DXd + capecitabine (C); (3) T-DXd + durvalumab; (4) T-DXd + 5-FU or C + oxaliplatin (Ox); or (5) T-DXd + 5-FU or C + durvalumab. In part 2 (dose expansion), pts with no prior treatment for metastatic disease will be randomized across 4 arms: (1) T-DXd; (2) trastuzumab + 5-FU or C + Ox or cisplatin; (3) T-DXd + 5-FU or C ± Ox; or (4) T-DXd + 5-FU or C + durvalumab. In part 2, pts will be stratified by HER2 status. Primary endpoints are safety, determination of recommended phase 2 doses (part 1), and investigator-assessed confirmed ORR per RECIST v1.1 (part 2). Secondary endpoints include confirmed ORR (part 1), disease control rate, duration of response, progression-free survival (all per investigator), OS, safety (part 2), pharmacokinetics, and immunogenicity. Clinical trial information: NCT04379596.

scholarly journals Detection of chimeric BCR-ABL genes on bone marrow samples and blood smears in chronic myeloid and acute lymphoblastic leukemia by in situ hybridization

Blood ◽  
1994 ◽  
Vol 83 (7) ◽  
pp. 1922-1928 ◽  
Author(s):  
M Bentz ◽  
G Cabot ◽  
M Moos ◽  
MR Speicher ◽  
A Ganser ◽  
...  
Keyword(s):  
In Situ Hybridization ◽  
Acute Lymphoblastic Leukemia ◽  
Yeast Artificial Chromosome ◽  
Lymphoblastic Leukemia ◽  
Philadelphia Chromosome ◽  
High Specificity ◽  
Breakpoint Cluster Region ◽  
Cluster Region ◽  
Blood Smears

Abstract The presence of BCR-ABL fusion genes has important diagnostic and prognostic implications in chronic myeloid leukemia (CML) and acute lymphoblastic leukemia (ALL). The CML-specific chimeric BCR-ABL gene with a break involving the major breakpoint cluster region (M-bcr) of the BCR-gene has been detected by means of fluorescence in situ hybridization (FISH). In this study, we present a FISH protocol that allows the detection of breaks in both the major and the minor breakpoint cluster region (m-bcr). Three hybridization signals of D107F9, a yeast artificial chromosome (YAC)-derived probe spanning the breakpoint regions of the BCR gene, were indicative of the translocation events. To increase the specificity further, this probe was combined with cos-abl 8, a cosmid probe flanking the breakpoint within the ABL gene for dual-color hybridization. Samples of 21 patients with CML, the ALL-derived cell line SUP-B15, and of seven patients with Philadelphia chromosome (Ph1)-positive ALL (three of them with breakpoints within m-bcr) were examined. BCR-ABL fusion was detected in all cases with high specificity (false-positive nuclei: mean, 0.1%). On cytogenetic preparations, the percentages of BCR-ABL- positive interphase cells ranged from 53% to 91%. Comparable efficiencies were achieved on blood smears. In conclusion, hybridization with D107F9 and cos-abl 8 allows unambiguous diagnosis of BCR-ABL genes and is likely to become an important tool for the monitoring of therapies in patients with CML and ALL.

Characterization of HER2 Status by Fluorescence In Situ Hybridization (FISH) and Immunohistochemistry (IHC)

2014 ◽  
pp. 181-207 ◽  
Author(s):  
Oliver A. Press ◽  
Roberta Guzman ◽  
Monica Cervantes ◽  
Angela Santiago ◽  
Michael F. Press
Keyword(s):  
In Situ Hybridization ◽  
Fluorescence In Situ Hybridization ◽  
Her2 Status
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