Homeoprotein DLX4 expression is increased in inflammatory breast cancer cases from an urban African-American population.

Jaehong Jeong,Kepher H Makambi,Jan K Blancato,Martin S Ongkeko,Aileen I Fernandez,Tammey J Naab

doi:10.18632/oncotarget.25790

Abstract

Protein expression of Distal-less homeobox 4 (DLX4) was analyzed in inflammatory breast cancer (IBC) cases from an African-American (AA) population to determine if a) DLX4 gene over expression exists in this cohort and b) if the overexpression is associated with breast cancer clinicopathological characteristics (ER, PR, HER2, triple-negative). Twenty-nine blocks of formalin-fixed paraffin-embedded (FFPE) tissue from well-characterized human IBC cases were used for immunohistochemical staining (IHC). IHC results were assigned an intensity and percentage score. Percentage scores were assigned as 0, 1, 2, 3, or 4 and intensity scores were assigned 0, 1+, 2+ or 3+. For the analysis of the IHC, a percentage score of 3 or 4 and an intensity score of 2+ or 3+ were categorized as high. Chi-square or Fisher's exact tests were used to compare the high and low groups.In this cohort, 89.7% (26 out of 29) of IBC cases showed high percentages of positive cells staining for the DLX4 protein, while 40.0% (12 out of 30) of normal breast tissue from reduction mammoplasty cases demonstrated DLX4 expression (p < 0.01). In IBC patients, 65.5% of cases showed a high level of staining intensity, compared to 20.0% of normal breast tissues (test, p = 0.001). Intensity to DLX4 was higher in the HER2 negative status (78.3%) than the HER2 positive status (16.7%) (test, p = 0.011).DLX4 expression is higher in the IBC cases in this study of an urban AA population than in normal breast tissue cases. HER2 negative status is positively associated with high intensity of DLX4.

Highlights

Inflammatory breast cancer (IBC) is one of the most aggressive subtypes of breast cancer [1]
Protein expression of Distal-less homeobox 4 (DLX4) was analyzed in inflammatory breast cancer (IBC) cases from an African-American (AA) population to determine if a) Distal-less homeobox 4 gene (DLX4) gene over expression exists in this cohort and b) if the overexpression is associated with breast cancer clinicopathological characteristics (ER, progesterone receptor (PR), Human epidermal growth factor receptor type 2 (HER2), triple-negative)
The mechanism and pathway of DLX4 and its involvement in IBC maintenance and progression remains unknown, it has been suggested to be a marker for tumor aggressiveness [12]

Summary

Introduction

Inflammatory breast cancer (IBC) is one of the most aggressive subtypes of breast cancer [1]. As per the 8th edition of the American Joint Commission on Cancer (AJCC) Staging Manual a tumor is considered pT4 if it is of any size and is a direct extension to the chest wall and/or to the skin (ulceration or skin nodules) [2]. Cancer Protocol for invasive breast carcinoma, define inflammatory carcinoma as being pT4d. It is associated with histopathological findings and requires a specific clinical presentation: an indurated peau d’ orange appearance, in which one-third or more of the breast has diffuse erythema and edema. IBC is rare and at www.oncotarget.com presentation is both aggressive and progresses rapidly, with 30% of patients having distant metastases at the time of diagnosis [4]. The median overall survival of women with IBC is less than 4 years [5]

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