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, Clare; Quinn, Cecily

doi:10.1136/jclinpath-2018-205485

Cited by 39 publications

(27 citation statements)

References 49 publications

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“…5b, Supplementary Fig. 11), consistent with the disconnect between AR expression and AR signaling in breast cancer noted by others 26 . Also, for patient BCN1371, we did not observe significant upregulation of PI3K signaling (Fig.…”

Section: Exploration Of Response Features In Individual Non-pcr Casessupporting

confidence: 88%

Microscaled proteogenomic methods for precision oncology

et al. 2020

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Cancer proteogenomics promises new insights into cancer biology and treatment efficacy by integrating genomics, transcriptomics and protein profiling including modifications by mass spectrometry (MS). A critical limitation is sample input requirements that exceed many sources of clinically important material. Here we report a proteogenomics approach for core biopsies using tissue-sparing specimen processing and microscaled proteomics. As a demonstration, we analyze core needle biopsies from ERBB2 positive breast cancers before and 48-72 h after initiating neoadjuvant trastuzumab-based chemotherapy. We show greater suppression of ERBB2 protein and both ERBB2 and mTOR target phosphosite levels in cases associated with pathological complete response, and identify potential causes of treatment resistance including the absence of ERBB2 amplification, insufficient ERBB2 activity for therapeutic sensitivity despite ERBB2 amplification, and candidate resistance mechanisms including androgen receptor signaling, mucin overexpression and an inactive immune microenvironment. The clinical utility and discovery potential of proteogenomics at biopsyscale warrants further investigation.

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Section: Exploration Of Response Features In Individual Non-pcr Casessupporting

confidence: 88%

Microscaled proteogenomic methods for precision oncology

et al. 2020

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“…The five non-pCR cases were stained for the pan T-cell marker CD3 to validate these proteogenomic findings ( Figure 5D). Consistent with the active immune microenvironment ( Figure 5C Figure 5D) without activation of an androgen response signature or apocrine features ( Supplementary Figure 11), consistent, with the disconnect between AR expression and AR signaling in breast cancer noted by others 26 . Also, for patient BCN1371, we did not see significant upregulation of PI3K signaling ( Figure 5B) despite PIK3CA mutation (E545K), consistent, with the disconnects between PIK3CA mutation and effects when signaling was assessed by reverse phase protein array (RPPA) 19,27 .…”

Section: Proteomics and Phosphoproteomic Analyses Of Acute On-treatmesupporting

confidence: 87%

Microscaled Proteogenomic Methods for Precision Oncology

Satpathy

Jaehnig

Krug

et al. 2019

Preprint

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and MJE: Matthew.Ellis@bcm.edu Running title: Microscaled Proteogenomic Methods for Precision Oncology Satpathy et al., Microscaled Proteogenomic Methods for Precision Oncology 2 AbstractCancer proteogenomics integrates genomics, transcriptomics and mass spectrometry (MS)-based proteomics to gain insights into cancer biology and treatment efficacy. A proteogenomics approach was therefore developed for frozen core biopsies using tissue-sparing specimen processing with a "microscaled" proteomics workflow. For technical proof-of-principle, biopsies from ERBB2 positive breast cancers before and 48-72 hours after the first dose of neoadjuvant trastuzumabbased chemotherapy were analyzed. ERBB2 protein and phosphosite levels, as well as mTOR target phosphosites, were significantly more suppressed upon treatment in cases associated with pathological complete response, suggesting MS-based pharmacodynamics is achievable. Furthermore, integrated analyses indicated potential causes of treatment resistance including the absence of ERBB2 amplification (false-ERBB2 positive) and insufficient ERBB2 activity for therapeutic sensitivity despite ERBB2 amplification (pseudo-ERBB2 positive). Candidate resistance features in true-ERBB2+ cases, including androgen receptor signaling, mucin expression and an inactive immune microenvironment were observed. Thus, proteogenomic analysis of needle core biopsies is feasible and clinical utility should be investigated. enriched PDX (WHIM) models with ERBB2 protein expression. B. MUC1 immunohistochemistry (IHC) of WHIM8, WHIM35 and BCN1369.

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“…The apocrine subtype of triple-negative breast cancers is also recognized on the basis of gene-expression profiles. 11,12 The association between papillary lesions and apocrine changes represents a great challenge for breast pathologists. Papotti et al first reported areas of apocrine differentiation in papillary breast carcinomas with and without invasion.…”

Section: Discussionmentioning

confidence: 99%

“…9 Apocrine lesions, for many pathologists, imply an ER and PR negative status by definition. 10,11 Malignant apocrine tumors may be HER2 negative or positive, the tumor being triple-negative in the first setting. The apocrine subtype of triple-negative breast cancers is also recognized on the basis of gene-expression profiles.…”

Section: Discussionmentioning

confidence: 99%

Mixed Invasive Apocrine Papillary/Micropapillary Carcinoma of the Breast: Another Brick in the Triple-Negative Wall

et al. 2020

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Pure invasive papillary carcinoma (IPC) is a rare subtype of breast carcinoma with good prognosis compared with classical invasive breast carcinoma (IBC) of no special type. The majority of IPC are estrogen receptor and progesterone receptor (ER/PR) positive and HER2 negative (luminal A-like). We report the case of a 72-year-old women who was referred to the Senology Clinic for a routine workup following surgery for an intraductal papilloma. The core needle biopsy (CNB) showed a lesion mainly composed of irregular papillae and micropapillae with apocrine epithelial cells of low-to-intermediate nuclear grade, without a myoepithelial cell layer within the papillae and at the periphery, as demonstrated with multiple immunostains. The diagnosis of apocrine papillary lesion of uncertain malignant potential was made. The subsequent lumpectomy showed an IBC with the same cyto-architectural features as the CNB. In addition, lymphovascular invasion and papillary/micropapillary apocrine in situ lesion were noted. Notably, the tumor was ER/PR and HER2 negative and strongly positive for androgen receptor. A final diagnosis of mixed apocrine papillary/micropapillary carcinoma with triple-negative status was made. To the best of our knowledge, this is the first report of an IBC with these features. Breast pathologists should be aware of this entity when dealing with CNB samples characterized by a complex papillary lesion with apocrine atypia that lacks a myoepithelial cell layer on multiple immunostains. These lesions should be classified at least as of uncertain malignant potential based on the cyto-architectural features prompting a surgery for removal.

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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

Cited by 39 publications

References 49 publications

Microscaled proteogenomic methods for precision oncology

Microscaled proteogenomic methods for precision oncology

Microscaled Proteogenomic Methods for Precision Oncology

Mixed Invasive Apocrine Papillary/Micropapillary Carcinoma of the Breast: Another Brick in the Triple-Negative Wall

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