HER2 genetic heterogeneity in breast carcinoma

2011 ◽  
Vol 64 (12) ◽  
pp. 1112-1116 ◽  
Author(s):  
Christian Öhlschlegel ◽  
Katharina Zahel ◽  
Doris Kradolfer ◽  
Margreth Hell ◽  
Wolfram Jochum

AimsTo determine the frequency of HER2 genetic heterogeneity according to the recent American Society of Clinical Oncology (ASCO) and College of American Pathologists (CAP) definition (2009) in invasive breast carcinoma, and to identify clinicopathological features that characterise breast carcinomas with HER2 genetic heterogeneity.Methods530 invasive breast carcinomas were retrospectively analysed for HER2 genetic heterogeneity, and investigated for a potential association of HER2 genetic heterogeneity with other HER2 FISH findings, clinicopathological parameters, oestrogen/progesterone receptor expression and DNA cytometric parameters in breast carcinomas with an equivocal (2+) HER2 immunohistochemical score.ResultsThe overall frequency of HER2 genetic heterogeneity was 14.7% in a cohort of 218 consecutive breast carcinomas. HER2 genetic heterogeneity was most frequent in invasive breast carcinomas with an equivocal (2+) HER2 immunohistochemical score. Among the 151 carcinomas lacking HER2 amplification, 16.1% showed HER2 genetic heterogeneity. In an extended cohort of 345 carcinomas with a (2+) HER2 score, the frequency of HER2 genetic heterogeneity was 41%, and was associated with the absence of HER2 gene clusters, chromosome 17 polysomy, histological tumour grade, DNA ploidy category and 5c exceeding rate.ConclusionHER2 genetic heterogeneity according to the ASCO/CAP definition is frequent in breast carcinoma, and is most often present in carcinomas with an equivocal (2+) HER2 score. Many carcinomas with HER2 genetic heterogeneity have a negative HER2 amplification status, although they contain a significant number of tumour cells with HER2 gene amplification. Single cell scoring of the HER2/17 centromeric probe (CEP17) ratio is necessary to identify carcinomas with HER2 genetic heterogeneity, because they lack specific clinicopathological characteristics.

2018 ◽  
Vol 142 (12) ◽  
pp. 1511-1516 ◽  
Author(s):  
Brannan B. Griffin ◽  
Jennifer L. Pincus ◽  
Kalliopi P. Siziopikou ◽  
Luis Z. Blanco

Context.— HER2 status is a prognostic factor and therapeutic target in invasive breast carcinomas. Reflex testing using an alternate method is recommended on equivocal cases via immunohistochemistry or fluorescence in situ hybridization (FISH). Therapeutic dilemmas arise when both tests are equivocal. The standard chromosome 17 centromere reference probe (CEP17) is in close proximity to the HER2 locus and may be coamplified, leading to equivocal results. Alternate chromosome 17 reference probes may aid in establishing the true HER2 status. Objective.— To describe our institutional experience using D17S122 probe for reflex FISH testing on double-equivocal invasive breast carcinomas and review the literature on alternate reference probes. Data Sources.— Twenty-two patients with double-equivocal invasive breast carcinomas, defined as HER2 immunohistochemistry score 2+ and FISH equivocal per the 2013 guidelines, were reviewed. Reflex FISH was performed with alternate probe D17S122 and the HER2 status classified for 11 cases by using a revised HER2:D17S122 ratio. Seven of 11 cases (63.6%) were ultimately classified as HER2 positive, while 4 cases (36.4%) remained equivocal. The 7 positive cases showed a HER2:D17S122 greater than 2.0. Conclusions.— Alternate probe D17S122 reclassified more than half of our cases as HER2 positive. Alternate probes may establish true HER2 status and direct proper management, as evidenced by our experience and the literature. Additional investigation is needed to determine which alternate probe(s) is(are) best for reflex testing. Finally, the American Society of Clinical Oncology/College of American Pathologists guidelines may need to be updated to reflect more specific recommendations for the utilization of appropriate probes in double-equivocal HER2 cases.


2019 ◽  
pp. 10-13

Invasive ductal carcinoma (IDC) is the most common histopathological type of breast cancer, accounting for up to 85% of all invasive breast carcinomas [1]. It spreads usually to the bone first. Solitary metastasis is commonly located in the lung, liver or brain [2]. Adrenal glands locations are extremely rare [3]. We report a case of isolated metachronous right adrenal metastasis, diagnosed four years after breast IDC management. The aim is to highlight clinical, diagnostic and therapeutic characteristics of this entity.


2013 ◽  
Vol 138 (2) ◽  
pp. 213-219 ◽  
Author(s):  
Kurt A. Schalper ◽  
Sudha Kumar ◽  
Pei Hui ◽  
David L. Rimm ◽  
Peter Gershkovich

Context.—In 2007 the American Society of Clinical Oncology/College of American Pathologists made new recommendations for HER2 testing and redefined HER2 positivity. Objective.—To analyze results from simultaneous HER2 testing with immunohistochemistry and fluorescence in situ hybridization (FISH) in 2590 invasive breast carcinomas between 2002 and 2010, using 2 scoring systems. Design.—Cases from between 2002 and 2006 were scored by using original US Food and Drug Administration criteria (N = 1138) and those from between 2007 and 2010 were evaluated according to American Society of Clinical Oncology/College of American Pathologists criteria (N = 1452). Concordance between testing methods and clinicopathologic associations were determined. Results.—Overall concordance between immunohistochemistry/FISH in the 9-year period was 96.2% (κ = 0.82), and positive concordance was lower. After 2007, the proportion of HER2/neu-positive and HER2/neu-negative cases was not significantly changed when using immunohistochemistry (10.5% versus 8.9%, P = .22 and 69.4% versus 63%, P = .13, respectively), but the number of equivocal cases was higher (19.9% versus 28%, P < .001). While the proportion of negative cases by FISH remained unchanged after 2007 (86.5% versus 88.2%, P = .76), the number of positive cases was lower (13.4% versus 9.2%, P < .001). In addition, 38 cases (2.6%) were FISH equivocal, 16 of which were also equivocal by immunohistochemistry. Overall, immunohistochemistry/FISH concordance was 95.9% between 2002 and 2006 (κ = 0.82) and 96.4% after 2007 (κ = 0.82). However, an approximately 13% lower positive assay concordance was noted in the last period. Conclusions.—Application of American Society of Clinical Oncology/College of American Pathologists recommendations is associated with comparable overall immunohistochemistry/FISH concordance, reduced positive concordance, and increased equivocal results.


2019 ◽  
pp. 10-12

Invasive ductal carcinoma (IDC) is the most common histopathological type of breast cancer, accounting for up to 85% of all invasive breast carcinomas [1]. It spreads usually to the bone first. Solitary metastasis is commonly located in the lung, liver or brain [2]. Adrenal glands locations are extremely rare [3]. We report a case of isolated metachronous right adrenal metastasis, diagnosed four years after breast IDC management. The aim is to highlight clinical, diagnostic and therapeutic characteristics of this entity.


PeerJ ◽  
2019 ◽  
Vol 7 ◽  
pp. e6903 ◽  
Author(s):  
Bin Wang ◽  
Huayong Jiang ◽  
Tingyang Zhou ◽  
Ning Ma ◽  
Wei Liu ◽  
...  

Background Inducible co-stimulator (ICOS) is a CD28-related molecule exclusively expressed on activated T cells and plays a critical role in modulating the immune response in breast cancer. The blockage of ICOS pathway has been shown to inhibit the activity of Type 2 T helper cells, thus potentially protecting against cancer growth. The current study aims to investigate the correlation between inducible co-stimulator ligand (ICOSL) expression in tumor tissues and the prognoses of patients with invasive breast cancer. Methods Tumor samples from 562 Chinese patients with invasive breast carcinomas were collected between 2003 and 2010. The expression of ICOSL on breast tumor and adjacent non-cancerous tissue was determined via immunohistochemistry. The overall survival (OS) of patients with positive and negative ICOSL expression were described using Kaplan–Meier curves, respectively. Parametric correlation method was used to analyze the correlation between ICOSL expression and other clinicopathological parameters. ICOSL was selected as a dependent variable for multivariate analysis. Results Positive ICOSL expression was identified on the plasma membrane in both cytoplasm and the nucleus of breast cancer cells. Membrane-expressed ICOSL is determined as an independent prognostic factor for OS in breast cancer but without significantly correlating with other clinicopathologic parameters such as age, menopausal status, depth of invasion, lymph node metastasis status, histologic classification, etc. Conclusion Our study suggests that the up-regulated expression of ICOSL protein in breast tumor cells can be associated with poor prognoses in invasive breast carcinomas.


2019 ◽  
pp. 10-12

Invasive ductal carcinoma (IDC) is the most common histopathological type of breast cancer, accounting for up to 85% of all invasive breast carcinomas [1]. It spreads usually to the bone first. Solitary metastasis is commonly located in the lung, liver or brain [2]. Adrenal glands locations are extremely rare [3]. We report a case of isolated metachronous right adrenal metastasis, diagnosed four years after breast IDC management. The aim is to highlight clinical, diagnostic and therapeutic characteristics of this entity.


2017 ◽  
Vol 59 (1) ◽  
pp. 50-57 ◽  
Author(s):  
Eun Young Yoo ◽  
Sang Yu Nam ◽  
Hye-Young Choi ◽  
Min Ji Hong

Background There may be discordance between tumor size determined by magnetic resonance imaging (MRI) and that observed during pathologic analyses. Purpose To evaluate MRI-pathology concordance of tumor size in patients with invasive breast carcinoma. Material and Methods Data from 307 invasive breast carcinomas were analyzed retrospectively. Preoperative breast MRI was reviewed for size, lesion type, morphology, and dynamic contrast-enhanced tumor kinetics. MRI tumor size was compared with tumor size measurements from the pathologic analysis. Concordance was defined as a difference in diameter of ≤ 0.5 cm. MRI-pathology concordance was compared according to clinical and histopathologic features. Results The mean tumor size on MRI was 2.48 ± 1.41 cm. Tumor measurements determined by MRI were not significantly different from those recorded in the pathologic reports (2.56 ± 1.61 cm, P = 0.199). MRI-pathology concordance was found in 229/307 (74.6%) cases; the size was overestimated in 36 (11.7%) tumors and underestimated in 42 (13.7%). On univariate analysis, MRI-pathology discordance was associated with larger tumor size ( P < 0.001), estrogen receptor (ER) negativity ( P = 0.006), and lymphovascular invasion ( P = 0.003). Human epidermal growth factor receptor 2 positive molecular subtype showed worse correlation between the tumor size measured by MRI and pathology compared with luminal A and luminal B subtypes ( P = 0.008 and 0.007). On multivariate analysis, tumor size and ER status significantly influenced MRI-pathology concordance ( P < 0.05). Conclusion ER negativity and larger tumor size were strongly associated with MRI-pathology discordance in invasive breast carcinomas. Awareness of these factors might improve surgical planning.


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