Breast cancer patients who develop a recurrence in the chest wall after mastectomy represent a high-risk subgroup that may benefit from early identification and more aggressive treatment. Traditional clinicopathologic factors have been proven useful for prognosis, but there remains a need to identify molecular markers with prognostic significance.
Sibo Tian, BA, Atif Khan, MD, Bruce G. Haffty, MD, Sinae Kim, PhD, Meena Moran, MD, Neil K. Taunk, MD, Hao Wu, PhD, Sharad Goyal, MD; Robert Wood Johnson Medical School; The Cancer Institute of New Jersey
Background: Breast cancer patients who develop a recurrence in the chest wall after mastectomy represent a high-risk subgroup that may benefit from early identification and more aggressive treatment. Traditional clinicopathologic factors have been proven useful for prognosis, but there remains a need to identify molecular markers with prognostic significance. Metadherin (MTDH) is an oncogene that is overexpressed in all cancers studied so far. It has been linked to multiple pathways, including PI3K/Akt, NFkB, and Wnt/ Î²-catenin, and is a key mediator of proliferation, metastasis, and chemoresistance. MTDH, while normally absent from human breast tissue, is overexpressed in 44% of primary breast tumors. The purpose of this study is to evaluate the association between MTDH expression and locoregional recurrence in a cohort of breast cancer patients treated with mastectomy.
Patients and Methods: We retrospectively identified 22 patients who developed a locoregional recurrence as the first or only site of failure after mastectomy and had paraffin-embedded tissue blocks from the primary tumor available. These patients were case control–matched to 28 patients who were disease-free at last follow-up. They were matched with respect to age (± 3 yr) and follow-up duration (< 5 or ≥ 5 yr). All patients initially presented with 0–3 positive nodes, and none received postmastectomy RT. Tumor blocks were assembled into a tissue microarray, and MTDH expression was analyzed by immunohistochemical methods and then quantified electronically based on the intensity of staining. Conditional logistic regression was used to test the relationship between each variable and the risk of locoregional recurrence.
Results: Immunohistochemical analysis revealed primarily cytoplasmic expression of MTDH, and 26 of 49 (53.1%) patients were positive for MTDH overexpression. Higher levels of MTDH expression were significantly associated with lower Ki67 expression (P = .006). Lower MTDH expression was linked to the triple-negative phenotype (P = .0027). In a univariate conditional logistic regression, lower MTDH expression was strongly linked to higher odds of locoregional recurrence (odds ratio [OR] = 0.062; 95% confidence interval [CI], 0.008–0.477; P = .0076).
Conclusions: We demonstrate, using a matched case-control design, that MTDH overexpression is significantly associated with improved locoregional control after mastectomy in a cohort of patients presenting with 0–3 positive nodes.