BackgroundAerobic glycolysis rate is higher in breast cancer tissues than adjacent normal tissues which providethe ATP, lactate and anabolic precursors required for tumourgenesis and metastasis. Lactate dehydrogenase (LDH) is a critical enzyme during aerobic glycolysis as it is typically responsible for the production of lactate and regeneration of NAD+, which allows for the continued functioning of glycolysis even in the absence of oxygen. LDH has been found to be highly expressed in breast tumors. Enzyme kinetic characteristics is related to environmentinvolving the enzyme, and tumor microenvironment has distinct features relative to adjacent normal tissues, thus we hypothesized that LDH should have different kinetic characteristics in breast tumors compared to normal breast tissues.MethodsLDH was partially purifiedfrom human breast tumors and normal tissues, which were obtained directly from operating room. TheMichaelis-Menten constant (Km), maximum velocity (Vmax), activation energy (Ea) and enzyme efficiency in breast tumors and normal tissueswere determined.ResultsIt was found that tumor LDH affinity in forward reaction was the same as normal LDH but Vmax of cancerous LDH was higher relative to normal LDH. In reverse reaction, affinity of tumor LDH for lactate and NAD+ was lower than normal LDH, also enzyme efficiency for lactate and NAD+ was higher in normal samples. The Ea of reverse reaction was higher in cancerous tissues.ConclusionsIt was concluded that thelow LDH affinity for lactate and NAD+ is a valuable tool for preserving lactate by cancer cells. We also conclude that increasing of LDH affinity may be a valid molecular target to abolish lactate dependent tumor growth and kinetic characteristics of LDH could be a novel diagnostic parameter for human breast cancer.

A 33 year-old breast-feeding woman presented with a left breast mass for 6 months. The mass was first noticed during her pregnancy. Physical examination showed an upper inner quadrant nontender mass without skin changes or axillary lymphadenopathy. Mammography revealed a round 6-cm density with smooth borders. Ultrasound showed mixed echogenicity. Computerized tomography (CT) scan was negative elsewhere. A 14G core needle biopsy (CNB) was performed. Pathology examination reported lactational change with focal dilated vascular spaces, and recommended clinical and radiologic correlation (Fig. 1). Due to clinical suspicion the patient underwent a wide local excision (WLE) (Fig. 2). Pathology examination revealed grade III angiosarcoma with clear surgical margins (Figs 3 and 4). Tumor cells were positive for CD34, negative for human herpes virus 8 (HHV8) and epithelial membrane antigen (EMA). Review of the initial CNB revealed grade I angiosarcoma and lactational changes. Adjuvant chemotherapy and radiotherapy were implemented postoperatively. Nine months after the left WLE, patient developed two right breast Figure 2. Core biopsy: Bland-appearing vascular spaces with architecturally atypical infiltration in the fibrous stroma and adipose tissue. Lack of conspicuous cytologic atypia is a pit fall in diagnosis of low-grade angiosarcoma in core biopsy and fine-needle aspiration specimens (H&E stain, original magnification 940).Figure 1. Core biopsy: Lactational changes (left lower) and scattered vascular spaces (right upper) (H&E stain, original magnification 940).