Comparative Pathologic Analysis of Breast Cancers Classified as HER2/neu-Amplified by FISH Using a Standard HER2/CEP17 Dual Probe and an Alternative Chromosome 17 Control Probe

2018 ◽  
Vol 42 (9) ◽  
pp. 1208-1215 ◽  
Author(s):  
Somaye Zare ◽  
Leo Lin ◽  
Abrar G. Alghamdi ◽  
Svenja Daehne ◽  
Andres A. Roma ◽  
...  
2012 ◽  
Vol 15 (1) ◽  
pp. 24 ◽  
Author(s):  
Aeri Kim ◽  
Hyung Chan Shin ◽  
Young Kyung Bae ◽  
Min Kyoung Kim ◽  
Su Hwan Kang ◽  
...  
Keyword(s):  

2019 ◽  
Vol 144 (5) ◽  
pp. 597-601 ◽  
Author(s):  
Raza S. Hoda ◽  
Edi Brogi ◽  
Jin Xu ◽  
Katia Ventura ◽  
Dara S. Ross ◽  
...  

Context.— The American Society of Clinical Oncology/College of American Pathologists HER2 testing guideline in breast cancer was updated in 2018 to address issues on interpretation of uncommon results using dual-probe in situ hybridization according to the 2013 guideline. Objective.— To assess impact of the 2018 guideline on breast cancer with equivocal HER2 immunohistochemistry results. Design.— We retrospectively reviewed HER2 fluorescence in situ hybridization (FISH) data (HER2/CEP17 ratio and average HER2 copy number per cell) of HER2 immunohistochemistry–equivocal (2+ or 1+ to 2+) breast cancers at our center between January 2014 and May 2018 and compared HER2 FISH results according to 2013 and 2018 guidelines. Results.— A total of 1666 HER2 FISH results from 1421 patients with equivocal HER2 immunohistochemistry were reviewed. Based on the 2013 guideline, HER2 FISH results were amplified in 346 cases (20.8%), equivocal in 242 (14.5%), and nonamplified in 1078 (64.7%). Using the 2018 guideline, 258 cases (16%) were reclassified, including 242 previously equivocal test results (15%) and 16 previously positive results (1%) reclassified as negative. The subset of 2013 HER2-equivocal and 2018 HER2-nonamplified cases with HER2/CEP17 ratio lower than 2.0 and average HER2 copy number 4.0 or higher and lower than 6.0 showed higher incidence of micropapillary morphology compared with HER2-amplified cases. Despite most patients in this group not receiving HER2-targeted treatment, 96% had no evidence of disease at follow-up. Conclusions.— The 2018 guideline eliminated HER2 FISH–equivocal cases by reclassifying HER2-equivocal cases and cases with nonclassical amplification without HER2 overexpression as HER2 negative. As a consequence, we observed a considerable increase in HER2 FISH–negative cases and a slight decrease in HER2 FISH–positive cases.


2001 ◽  
Vol 7 (5) ◽  
pp. 337-344 ◽  
Author(s):  
Shikha Bose ◽  
Mansoor Mohammed ◽  
Peter Shintaku ◽  
P. Nagesh Rao

2015 ◽  
Vol 14 (9) ◽  
pp. 3519-3529 ◽  
Author(s):  
Rajasree Menon ◽  
Bharat Panwar ◽  
Ridvan Eksi ◽  
Celina Kleer ◽  
Yuanfang Guan ◽  
...  

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e11600-e11600
Author(s):  
D. Miura ◽  
Y. Saitoh ◽  
T. Iwatani ◽  
H. Kawabata ◽  
N. Inoshita

e11600 Background: Precise assessment of HER-2 is critical in breast cancers and predicts benefit of trastuzumab (T). Although subset analysis of CALGB 9840 suggests benefit in FISH-negative patients with chromosome 17 polysomy (C17), clinical significance of C17 in FISH-positive patients is still less known. To analyze the epidemiologic feature of C17 in Japanese patients, consecutive operable breast cancer patients during 05–07 treated in single institution were studied. Methods: HER-2 status of consecutive 307 patients excluding DCIS and whose specimens were poor quality for study, were analyzed with Pathvysion (FISH). We defined HER- 2 (+) and C17 as HER-2/chromosome 17 ratio ≥ 2.2 and CEP ratio ≥ 2.2, respectively. Pathological response following neoadjuvant chemotherapy (NACT) was assigned according to the Japanese Breast Cancer Society (G3; no invasive or in situ residual tumor in the breast, G2; up to two thirds of primary cancer cells having pathologically severe changes or disappearance, G1; up to one third to two thirds of primary cancer cells having pathologically severe changes or disappearance). Results: HER-2 (+) was found in 22% (67/307) and C17 in 25% (77/307). Twenty-four of 67(36%) in HER-2 (+) had C17 and 53 of 240 (22%) in HER-2 (-) did C17. Among HER-2 (+), 23 cases received T-contained regimens as NACT (FEC/EC followed by PAC+T in 18 and DOC+CPA+T in 5). Six of 9 (67%) with C17 had G3 and 2 of 14 (14%) with non-C17 did G3. CEP ratio significantly predicts to have G3 (p=0.02) but HER-2/chromosome 17 ratio by logistic regression analysis. Conclusions: C17 was found in 25% of Japanese operable breast cancer patients of which was similar to that of CALGB. CEP ratio is a good predictive marker for chemo- sensitivity in HER-2 (+) subset. No significant financial relationships to disclose.


2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e12002-e12002
Author(s):  
Robert W. Galamaga ◽  
Rachel Mariani ◽  
Imad Almanaseer ◽  
Jacob D. Bitran

e12002 Background: Human epidermal growth factor receptor 2 (HER-2) overexpression occurs in up to 30% of breast cancers and has been associated with poor clinical outcomes that have improved with advances in HER-2 directed therapy. The HER-2 gene resides on the long arm of chromosome 17 and amplification is typically assessed via immunohistochemistry or fluorescence in situ hybridization (FISH); HER-2 is interpreted as amplified, non-amplified, or equivocal. The effect and clinical impact of chromosome 17 polysomy in specimens interpreted as HER-2 non-amplified has not been well-established in breast cancer patients. This subgroup may represent a unique set of patients who may benefit from HER-2 directed therapy given the increase in HER-2 gene copy number. If tumors with polysomy 17 share biologic similarities with those positive for HER-2 amplification this may significantly influence the approach to treating these patients. In a single institution study we reviewed all breast cancer cases diagnosed in 2008 which were reported as HER-2 equivocal or non-amplified via FISH and with chromosome 17 polysomy in order to extrapolate disease-free and overall survival data within this subset. Methods: HER-2 expression via FISH from patients diagnosed with breast cancer in 2008 was reviewed. In those patients with equivocal or non-amplified HER-2 expression we selected those with chromosome 17 polysomy defined as a chromosome 17 centromere copy number of > 3 per tumor cell. A total of 9 patients were identified. Results: The median age was 74 (36-88). Median tumor size was 1.6 cm (0.7-4.9) and 8 patients (88%) had both estrogen and progesterone positive tumors. Stage distribution was as follows: stage IA: 4 (44%); stage IIA: 2 (22%); stage IIB: 2 (22%) and stage IIIA: 1 (11%). The actuarial 3 year disease free survival was 67%. Conclusions: Breast cancers with equivocal or non-amplified HER-2 expression with chromosome 17 polysomy represent a unique subset of tumors with a biology that is not well-understood. Previously published studies have yielded conflicting results regarding the prognostic significance of this genotype. Our study reflects a three year survival of 67% which suggests that these patients represent an aggressive subset.


2000 ◽  
Vol 191 (10) ◽  
pp. 1675-1686 ◽  
Author(s):  
Jürgen Janke ◽  
Kathrin Schlüter ◽  
Burkhard Jandrig ◽  
Michael Theile ◽  
Konrad Kölble ◽  
...  

Differential display screening was used to reveal differential gene expression between the tumorigenic breast cancer cell line CAL51 and nontumorigenic microcell hybrids obtained after transfer of human chromosome 17 into CAL51. The human profilin 1 (PFN1) gene was found overexpressed in the microcell hybrid clones compared with the parental line, which displayed a low profilin 1 level. A comparison between several different tumorigenic breast cancer cell lines with nontumorigenic lines showed consistently lower profilin 1 levels in the tumor cells. Transfection of PFN1 cDNA into CAL51 cells raised the profilin 1 level, had a prominent effect on cell growth, cytoskeletal organization and spreading, and suppressed tumorigenicity of the stable, PFN1-overexpressing cell clones in nude mice. Immunohistochemical analysis revealed intermediate and low levels of profilin 1 in different human breast cancers. These results suggest profilin 1 as a suppressor of the tumorigenic phenotype of breast cancer cells.


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