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. 2013 May 11;15(3):R37.
doi: 10.1186/bcr3421.

Molecular apocrine breast cancers are aggressive estrogen receptor negative tumors overexpressing either HER2 or GCDFP15

Jacqueline Lehmann-Che, Anne-Sophie Hamy, Raphaël Porcher, Marc Barritault, Fatiha Bouhidel, Hanadi Habuellelah, Solenne Leman-Detours, Anne de Roquancourt, Laurence Cahen-Doidy, Edwige Bourstyn, Patricia de Cremoux, Cedric de Bazelaire, Marcela Albiter, Sylvie Giacchetti, Caroline Cuvier, Anne Janin, Marc Espié, Hugues de Thé, Philippe Bertheau

Molecular apocrine breast cancers are aggressive estrogen receptor negative tumors overexpressing either HER2 or GCDFP15

Jacqueline Lehmann-Che et al. Breast Cancer Res. .

Abstract

Introduction: Molecular apocrine (MA) tumors are estrogen receptor (ER) negative breast cancers characterized by androgen receptor (AR) expression. We analyzed a group of 58 transcriptionally defined MA tumors and proposed a new tool to identify these tumors.

Methods: We performed quantitative reverse transcription PCR (qRT-PCR) for ESR1, AR, FOXA1 and AR-related genes, and immunohistochemistry (IHC) for ER, PR, Human Epidermal Growth Factor Receptor 2 (HER2), CK5/6, CK17, EGFR, Ki67, AR, FOXA1 and GCDFP15 and we analyzed clinical features.

Results: MA tumors were all characterized by ESR1(-) AR(+) FOXA1(+) and AR-related genes positive mRNA profile. IHC staining on these tumors showed 93% ER(-), only 58% AR(+) and 90% FOXA1(+). 67% and 57% MA tumors were HER2(3+) and GCDFP15(+), respectively. Almost all MA tumors (94%) had the IHC signature HER2(3+) or GCDFP15(+) but none of the 13 control basal-like (BL) tumors did. Clinically, MA tumors were rather aggressive, with poor prognostic factors.

Conclusion: MA tumors could be better defined by their qRT-PCR-AR profile than by AR IHC. In addition, we found that HER2 or GCDFP15 protein overexpression is a sensitive and specific tool to differentiate MA from BL in the context of ER negative tumors. A composite molecular and IHC signature could, therefore, help to identify MA tumors in daily practice.

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Figures

Figure 1
Figure 1
Histopathological features of two molecular apocrine cases. Both cases show apocrine differentiation on H&E stainings, as well as positive immunostainings for HER2, GCDFP15 and FOXA1. AR immunostaining is positive in case A but negative in case B. AR, androgen receptor; HER2, Human Epidermal Growth Factor Receptor 2.
Figure 2
Figure 2
Relationship between AR and FOXA1 qRT-PCR and IHC in the MA and BL tumors groups. Positive cut-off ratio is 100. Boxplots indicate first quartile, median and third quartile. Outliers are indicated by small circles. AR, androgen receptor; BL, basal-like; IHC, immunohistochemistry; MA, molecular apocrine.
Figure 3
Figure 3
Distribution of the MA and BL tumors according to ER, HER2, GCDFP15 and AR immunostainings. Numbers of tumors in each subgroup are indicated. AR, androgen receptor; BL, basal-like; ER, estrogen receptor; HER2, Human Epidermal Growth Factor Receptor 2; MA, molecular apocrine.
Figure 4
Figure 4
Classification tree in the 67 ER(-) patients. Bold basal-like and molecular apocrine labels refer to the classification result at the terminal nodes of the tree (leafs). A and B denote the numbers of MA and BL tumor patients over the total number of patients at the nodes. BL, basal-like; ER, estrogen receptor; MA, molecular apocrine.
Figure 5
Figure 5
DFS and OS curves of the 58 MA and 13 BL tumors. DFS, disease free survival; OS, overall survival.
See this image and copyright information in PMC

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