Immunohistochemical and molecular profiling of histologically defined apocrine carcinomas of the breast

Vranić, Semir; Marchiò, Caterina; Castellano, Isabella; Botta, C.; Scalzo, Maria Stella; Bender, Ryan; Payán‐Gómez, César; Cantogno, Ludovica Verdun di; Gugliotta, Patrizia; Tondat, Fabrizio; Celle, Paola Francia di; Mariani, Sara; Gatalica, Zoran; Sapino, Anna

doi:10.1016/j.humpath.2015.05.017

Cited by 50 publications

(45 citation statements)

References 36 publications

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“…Based on this, AU565, BT474, and SKBR3 were defined as responsive, EFM-192A, HCC202, HCC1569, HCC1419, and MDA-MB-453 as intermediately responsive, and HCC1954, JIMT1, KPL4, SUM190PT, and SUM225 as nonresponsive (Table 1). MDA-MB-453 is known as an apocrine cell-line model, and HER2-positive apocrine breast carcinomas harbor alterations in the PI3K-signaling pathway 39,40. Cell lines with wild-type PIK3CA showed a better response to trastuzumab than cell lines with PIK3CA mutation ( P <0.001, Figure 3A).…”

Section: Resultsmentioning

confidence: 99%

Drug-screening and genomic analyses of HER2-positive breast cancer cell lines reveal predictors for treatment response

Jernström¹,

Hongisto²,

Leivonen³

et al. 2017

BCTT

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BackgroundApproximately 15%–20% of all diagnosed breast cancers are characterized by amplified and overexpressed HER2 (= ErbB2). These breast cancers are aggressive and have a poor prognosis. Although improvements in treatment have been achieved after the introduction of trastuzumab and lapatinib, many patients do not benefit from these drugs. Therefore, in-depth understanding of the mechanisms behind the treatment responses is essential to find alternative therapeutic strategies.Materials and methodsThirteen HER2 positive breast cancer cell lines were screened with 22 commercially available compounds, mainly targeting proteins in the ErbB2-signaling pathway, and molecular mechanisms related to treatment sensitivity were sought. Cell viability was measured, and treatment responses between the cell lines were compared. To search for response predictors and genomic and transcriptomic profiling, PIK3CA mutations and PTEN status were explored and molecular features associated with drug sensitivity sought.ResultsThe cell lines were divided into three groups according to the growth-retarding effect induced by trastuzumab and lapatinib. Interestingly, two cell lines insensitive to trastuzumab (KPL4 and SUM190PT) showed sensitivity to an Akt1/2 kinase inhibitor. These cell lines had mutation in PIK3CA and loss of PTEN, suggesting an activated and druggable Akt-signaling pathway. Expression levels of five genes (CDC42, MAPK8, PLCG1, PTK6, and PAK6) were suggested as predictors for the Akt1/2 kinase-inhibitor response.ConclusionTargeting the Akt-signaling pathway shows promise in cell lines that do not respond to trastuzumab. In addition, our results indicate that several molecular features determine the growth-retarding effects induced by the drugs, suggesting that parameters other than HER2 amplification/expression should be included as markers for therapy decisions.

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Section: Resultsmentioning

confidence: 99%

Drug-screening and genomic analyses of HER2-positive breast cancer cell lines reveal predictors for treatment response

Jernström¹,

Hongisto²,

Leivonen³

et al. 2017

BCTT

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“…Dard-Esfahani et al defined an MAT as a tumour with an ER/PR negative, AR positive IHC profile and noted a strong correlation with GCDFP-15 IHC positivity (67.9%) and apocrine morphology (60.7%) 18. Vranic et al have recently shown that addition of GCDFP-15 and HER2 to the standard IHC profile increases diagnostic sensitivity to 100% 19. IHC expression of gamma-glutamyl trasferase 1 (GGT-1) has also been shown to correlate with expression of the molecular apocrine signature20 and may be an adjunct to diagnosis 21…”

Section: Molecular Apocrine Tumoursmentioning

confidence: 99%

Apocrine lesions of the breast: part 2 of a two-part review. Invasive apocrine carcinoma, the molecular apocrine signature and utility of immunohistochemistry in the diagnosis of apocrine lesions of the breast

D’Arcy

Quinn

2018

J Clin Pathol

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Pure apocrine carcinoma of the breast is rare and has been defined by using a combination of morphologic (apocrine morphology in >90% of tumour cells) and immunohistochemical criteria (oestrogen receptor (ER) and progesterone receptor (PR) negative and androgen receptor (AR) positive). Recent advances in the molecular classification of breast tumours have uncovered a subset of breast tumours associated with high expression of androgen receptor mRNA including the so-called ‘luminal androgen receptor (LAR) tumours’ and ‘molecular apocrine tumours’ (MATs). Recognition of these tumour subsets has opened potential avenues for therapies exploiting the AR pathway in triple negative breast carcinoma (TNBC). In this second part of our two-part review, we focus on the definition of pure apocrine carcinoma, recent advances in understanding the molecular apocrine signature in breast carcinoma, its relationship to pure apocrine carcinoma defined at the level of light microscopy and immunohistochemistry (IHC) and the therapeutic implications of androgen expression in TNBC. We complete the article with a summary of the utility of IHC in stratifying apocrine lesions of the breast.

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“…Invasive apocrine adenocarcinoma (AAC) of breast is a rare histopathologically defined subtype of breast carcinoma, which is morphologically characterized by abundant eosinophilic and granular cytoplasm, large nuclei with prominent nucleoli, and distinctive cell membrane by hematoxylin and eosin (H&E) staining [1]. Furthermore, they tend to exhibit a characteristic hormone receptor profile: estrogen receptor (ER)-negative, progesterone receptor (PR)-negative and androgen receptor (AR)-positive, either human epidermal growth factor receptor-2 (HER2)-positive or (epidermal growth factor receptor) EGFR-positive [1–3].…”

Section: Introductionmentioning

confidence: 99%

“…Furthermore, they tend to exhibit a characteristic hormone receptor profile: estrogen receptor (ER)-negative, progesterone receptor (PR)-negative and androgen receptor (AR)-positive, either human epidermal growth factor receptor-2 (HER2)-positive or (epidermal growth factor receptor) EGFR-positive [1–3]. Although the immunohistochemical characteristics are helpful for the proper recognition of the apocrine carcinomas, the presence of malignant apocrine cells in more than 90% of the tumor population strictly defines AAC of breast [4].…”

Section: Introductionmentioning

confidence: 99%

Dose invasive apocrine adenocarcinoma has worse prognosis than invasive ductal carcinoma of breast: evidence from SEER database

Zhang

Chen

et al. 2017

Oncotarget

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BackgroundInvasive apocrine adenocarcinoma (AAC) of breast is a rare histopathological subtype of breast carcinomas. We aim to investigate the different characteristics and prognostic outcomes between AAC and invasive ductal carcinoma (IDC) of breast cancer.RESULTSAAC patients presented with older ages, more aggressive behaviors, lower ER and PR proportions, higher HER2 amplification rates and less application of breast-conserving therapy and adjuvant chemotherapy compared to IDC patients. Long-term OS and DSS were both worse in ACC patients (p = 0.006, p = 0.012 respectively) than in IDC patients by Kaplan-Meier analysis. However, no significant difference was detected in DSS (p = 0.181) and OS (p = 0.116) between the matched two histological subtypes. Further subgroup analysis indicated that AJCC stage, ER status, PR status and HER2 status may be principal confounders for AAC prognosis.Materials and MethodsWith accession to the Surveillance, Epidemiology and End Result (SEER) database, a total of 260,596 patients met the eligibility criteria. Clinicopathological characteristics were compared between groups using Chi-square test. Univariate and multivariate analyses were applied to evaluate the overall survival (OS) and disease-specific survival (DSS). Subgroup analyses summarized the hazard ratio (HR) of AAC versus IDC using a forest plot.ConclusionsAAC had unique clinicopathological characteristics and it tended to be a more aggressive type than IDC. However, the worse prognosis was diminished after matching for demographic and clinicopathological factors. Deeper insights into AAC are in need to contribute to individualized and tailored therapy, which thereby may improve clinical management and outcomes.

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Immunohistochemical and molecular profiling of histologically defined apocrine carcinomas of the breast

Cited by 50 publications

References 36 publications

Drug-screening and genomic analyses of HER2-positive breast cancer cell lines reveal predictors for treatment response

Drug-screening and genomic analyses of HER2-positive breast cancer cell lines reveal predictors for treatment response

Apocrine lesions of the breast: part 2 of a two-part review. Invasive apocrine carcinoma, the molecular apocrine signature and utility of immunohistochemistry in the diagnosis of apocrine lesions of the breast

Dose invasive apocrine adenocarcinoma has worse prognosis than invasive ductal carcinoma of breast: evidence from SEER database

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