Six1 Expression in Triple Negative Breast Carcinoma: Correlation with Prognostic Parameters and Outcome.
Harold C Sullivan, Amy Adams, Gabriela M Oprea, Andrew J Page, Cohen Cynthia. Emory University School of Medicine, Atlanta, GA
Background: Homeobox genes give rise to transcription factors that play an essential role in embryologic development. Misexpression of these genes is implicated in the development of cancers. One homeobox gene, homeobox 1 homolog homeoprotein, known as Six1, is overexpressed in hepatocellular, ovarian, and breast cancer. Six1 induces epithelial-mesenchymal transition in breast carcinoma cell lines and may be involved in metastasis. Patients with triple negative breast carcinoma (TNBrCa) have poorer prognostic factors and poorer survival compared to those with breast cancers that express hormones and/or HER2. TNBrCa demonstrate a propensity to metastasize to visceral organs. We studied TNBrCa for Six1 expression in relation to the aggressive nature and metastatic tendency of TNBrCa.
Design: 130 invasive TNBrCa were immunostained for Six1 in tissue microarrays (TMA) with 2 1mm cores of each carcinoma. Clinicopathologic criteria (age, tumor size, grade, lymph node status, angiolymphatic invasion) and survival data were obtained. Carcinoma TMAs were stained for CK5/6, CK7, CK8, CK14, CK18, CK19, p53, p63, topoisomerase, androgen receptor, Ki-67, c-kit, EGFR, p-cadherin, vimentin, and CD44. Clinicopathologic criteria, marker expression, and outcome (overall and recurrence free survival, dead of disease, recurrence) were compared in Six1-positive and -negative tumors.
Results: Six1 was present in 89 (69%) TNBrCa, 55 (74%) being African American and 34 (61%) Caucasian (p=0.098).
|Characteristic/marker||Six1-positive no. (%)||Six1-negative no. (%)||P-value|
|Tumor size (cm)||3.2||2.16||0.05|
|Grade III||72/97 (74)||25/97 (26)||0.047|
|Lymphovascular invasion||32/88 (36)||8/39 (21)||0.076|
|Metastases||32/79 (41)||8/36 (22)||0.056|
|Topoisomerase||68/86 (79)||22/35 (63)||0.064|
|Ki-67||73/85 (86)||19/37 (51)||<0.001|