Assessment of HER2 status in breast cancer: overall positivity rate and accuracy by fluorescence in situ hybridization and immunohistochemistry in a single institution over 12 years: a quality control study

Varga, Zsuzsanna; Noske, Aurelia; Ramach, Constanze; Padberg, Barbara; Moch, Holger

doi:10.1186/1471-2407-13-615

Cited by 96 publications

(126 citation statements)

References 38 publications

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“…45 In contrast, FISH allows for precise gene copy number determination in individual cells, rendering it independent from the purity of cancer tissues or presence of aneusomy. [46][47][48] 8p deletions were unevenly distributed between breast cancer subtypes, providing further support for the existence of biological differences between different subtypes of breast cancer. The higher rate of 8p deletions in NST as compared to lobular cancer is not surprising as most genomic alterations are more frequent in NST than in lobular carcinomas such as amplifications of HER2, 41,49 MYC, 41 MDM1, 41 and AIB1, 50 or overexpression of p53.…”

Section: Discussionmentioning

confidence: 70%

“…These findings are in line with previous studies reporting associations between 8p loss/LOH with adverse tumor phenotype [25][26][27][28][29] and poor clinical outcome. 25,27,29,31 Studies that could find associations of 8p deletions with tumor progression had involved remarkably small cohorts of 40, 35 44, 36 46, 33 52,38 55, 39 60, 14 61, 32 76 34 and 105 37 patients. The ability to detect a clinical utility of 8p deletion measurement in small cohorts is obviously caused by the high rate of positive cases (almost 50%) and a particularly strong prognostic impact of this feature.…”

Section: Discussionmentioning

confidence: 99%

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8p deletion is strongly linked to poor prognosis in breast cancer

Lebok

Mittenzwei

Kluth

et al. 2015

Cancer Biology & Therapy

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Deletions of chromosome 8p occur frequently in breast cancers, but analyses of its clinical relevance have been limited to small patient cohorts and provided controversial results. A tissue microarray with 2,197 breast cancers was thus analyzed by fluorescence in-situ hybridization using an 8p21 probe in combination with a centromere 8 reference probe. 8p deletions were found in 50% of carcinomas with no special type, 67% of papillary, 28% of tubular, 37% of lobular cancers and 56% of cancers with medullary features. Deletions were always heterozygous. 8p deletion was significantly linked to advanced tumor stage (P < 0.0001), high-grade (P < 0.0001), high tumor cell proliferation (Ki67 Labeling Index; P < 0.0001), and shortened overall survival (P < 0.0001). For example, 8p deletion was seen in 32% of 290 grade 1, 43% of 438 grade 2, and 65% of 427 grade 3 cancers. In addition, 8p deletions were strongly linked to amplification of MYC (P < 0.0001), HER2 (P < 0.0001), and CCND1 (p D 0.001), but inversely associated with ER receptor expression (p D 0.0001). Remarkably, 46.5% of 8p-deleted cancers harbored amplification of at least one of the analyzed genes as compared to 27.5% amplifications in 8p-non-deleted cancers (P < 0.0001). In conclusion, 8p deletion characterizes a subset of particularly aggressive breast cancers. As 8p deletions are easy to analyze, this feature appears to be highly suited for future DNA based prognostic breast cancer panels. The strong link of 8p deletion with various gene amplifications raises the possibility of a role for regulating genomic stability.

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Section: Discussionmentioning

confidence: 70%

Section: Discussionmentioning

confidence: 99%

8p deletion is strongly linked to poor prognosis in breast cancer

Lebok

Mittenzwei

Kluth

et al. 2015

Cancer Biology & Therapy

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“…This results were statistically significant (P<00.1). A few of studies [11,[17][18][19] show a concordance rate between IHC 3+ and discordance rate between IHC 2+ with FISH. But, other studies [14,20] show a concordance rate between IHC 2+ and FISH.…”

Section: Discussionmentioning

confidence: 99%

Comparison of IHC, FISH, ER and PR in Breast Cancer in Western Iran

Payandeh¹,

Sadeghi²,

Sadeghi³

et al. 2014

AJCP

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To evaluate the concordance and discordance between IHC and FISH results for detection of Her2/neu protein, analyses of ER and PR, and also evaluation of the benefit of adjuvant trastuzumab in patients diagnosed with human epidermal growth factor receptor 2 (HER2) -positive invasive ductal carcinoma enrolled onto the Herceptin adjuvant. IHC analysis of ER, PR and HER2 was performed in 133 patients of breast cancer with invasive ductal carcinoma. 90(67.6%) cases were confirmed by FISH. Statistical analysis was performed with IBM SPSS version 19, Kaplan-Meier method and log-rank test. Age mean of patients was 46.39±10.81 years (range, 24-78 years). Concordance rates between IHC and FISH were 32.4% for IHC 2+ and 81.25% for IHC 3+ (P<0.001). There were 17 and 56 patients of IHC 2+ and 3+ with ER positive and also 23 and 59 patients of IHC 2+ and 3+ had PR positive.The 83 patients had age ≤50 years and 50 patients had >50 years. Of 133 the patients, 48(36.1%) patients were treated with trastuzumab and 85(63.9%) were treated without trastuzumab. The overall survival(OS) for patients treating with trastuzumab were mean of 37.8 months and the OS for patients treating without trastuzumab were mean of 20.8 months (P<0.05). The results are that trastuzumab therapy is effective and improves the survival of HER2-positive breast cancer patients and trastuzumab therapy is effective and tolerated for breast cancer with Her-2 positive. There is a statistically significant relationship between ER positive with PR positive and ER negative with PR negative that these results need to more studies with more patients in the world.

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“…As examples, EGFR and ALK alterations in lung cancer (7)(8)(9), KRAS in colorectal cancer (as a marker of resistance; ref. 10), HER2 in breast cancer (11,12) or BRAF in melanoma (13)(14)(15) are frequently being tested, and the FDA has approved drugs for patients whose tumors bear aberrations in these genes. Indeed, increasingly, targeted therapies are being approved on the basis of the presence of a genomic alterations, for example, the BRAF inhibitors vemurafenib and dabrafenib, or the MEK inhibitor trametanib, for patients with tumors bearing a BRAF mutation (13)(14)(15).…”

Section: Introductionmentioning

confidence: 99%

Precision Oncology: The UC San Diego Moores Cancer Center PREDICT Experience

Schwaederlé¹,

Parker²,

Schwab³

et al. 2016

Molecular Cancer Therapeutics

161

136

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By profiling their patients' tumors, oncologists now have the option to use molecular results to match patients with drug(s) based on specific biomarkers. In this observational study, 347 patients with solid advanced cancers and next-generation sequencing (NGS) results were evaluated. Outcomes for patients who received a "matched" versus "unmatched" therapy following their NGS results were compared. Eighty-seven patients (25%) were treated with a "matched" therapy, 93 (26.8%) with an "unmatched" therapy. More patients in the matched group achieved stable disease (SD) ! 6 months/partial response (PR)/complete response (CR), 34.5% vs. 16.1%, (P 0.020 multivariable or propensity score methods). Matched patients had a longer median progression-free survival (PFS; 4.0 vs. 3.0 months, P ¼ 0.039 in the Cox regression model). In analysis using PFS1 (PFS on the prior line of therapy) as a comparator to PFS after NGS, as expected, the unmatched group demonstrated a PFS2 significantly shorter than PFS1 (P ¼ 0.009); however, this shortening was not observed in the matched patients (P ¼ 0.595). Furthermore, 45.3% of the matched patients (24/53) had a PFS2/ PFS1 ratio !1.3 compared with 19.3% of patients (11/57) in the unmatched group (P ¼ 0.004 univariable and P ! 0.057 in multivariable/propensity score analysis). Patients with a "matching-score" (the number of matched drugs divided by the number of aberrations; unmatched patients had a score of zero) > 0.2 had a median overall survival (OS) of 15.7 months compared with 10.6 months when their matching-score was 0.2, (P ¼ 0.040 in the Cox regression model). Matched versus unmatched patients had higher rates of SD ! 6 months/PR/CR and longer PFS, and improvement in OS correlated with a higher matching score in multivariable analysis. Mol Cancer Ther; 15(4); 743-52. Ó2016 AACR.

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Assessment of HER2 status in breast cancer: overall positivity rate and accuracy by fluorescence in situ hybridization and immunohistochemistry in a single institution over 12 years: a quality control study

Cited by 96 publications

References 38 publications

8p deletion is strongly linked to poor prognosis in breast cancer

8p deletion is strongly linked to poor prognosis in breast cancer

Comparison of IHC, FISH, ER and PR in Breast Cancer in Western Iran

Precision Oncology: The UC San Diego Moores Cancer Center PREDICT Experience

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