R&D News: Researchers find new noninvasive way to identify lymph node metastasis

The new procedure could spare breast cancer patients invasive and unreliable sentinel lymph node (SLN) biopsies and surgery-associated negative side effects.

Corresponding author David Morse said: “The majority of breast cancer patients, up to 74 percent, who undergo SLN biopsy are found to be negative for axillary nodal, or ALN, metastases.

“Determining the presence or absence of ALN metastasis is critical to breast cancer staging and prognosis. Because of the unreliability of the SLN biopsy and its potential for adverse effects, a noninvasive, more accurate method to assess lymph node involvement is needed.”

The authors note that the postoperative complications to the SLN biopsy can include lymphedema, seroma formation, sensory nerve injury and limitations in patient range of motion. In addition, biopsies fail to identify disease in axillary lymph nodes in five to 10 percent of patients.

In developing targeted molecular probes to identify breast cancer in axillary lymph nodes, the research team from Moffitt, the University of Arizona and University of Florida used two surface cell markers - CAIX and CAXII.

CAIX is a cell surface marker known to be ‘highly and broadly expressed in breast cancer lymph node metastases’ and absent in normal tissues.

CAIX and CAXII are both integral plasma membrane proteins with large extracellular components that are accessible for binding of targeted imaging probes, explained Morse. In addition, several studies have shown that CAIX expression is associated with negative prognosis and resistance to chemo and radiation therapy for breast cancer. CAXII is a protein expressed in over 75 percent of axillary lymph node metastases.

The researchers subsequently developed their targeting agents by using monoclonal antibodies specific for binding CAIX and CAXII, both of which are known to promote tumor growth.

According to the researchers, a number of noninvasive optical imaging procedures for SLN evaluation have been investigated, but the approaches have lacked the ability to target tumor metastasis biomarkers.

“These methods provide only anatomic maps and do not detect tumor cells present in lymph nodes,” explained Morse. “Using mouse models of breast cancer metastasis and a novel, monoclonal anti-body-based molecular imaging agents, we developed a targeted, noninvasive method to detect ALN metastasis using fluorescence imaging.”

In addition to the imaging study with mice, the researchers also reported that the combination of CAIX and CAXII covered 100 percent of patient-donated samples used in their tissue microarray (TMA) study.

“The imaging probes detected tumor cells in ALNs with high sensitivity,” explained Morse. "Either CAIX or CAXII were expressed in 100 percent of the breast cancer lymph node metasatsis samples we surveyed in this study. These imaging probes have potential for providing a noninvasive way to stage breast cancer in the clinic without unneeded and costly surgery.”

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Is anyone prepared to solve the NHS funding crisis?

As long as the political taboo on raising taxes endures, the service will be in financial peril. 

It has long been clear that the NHS is in financial ill-health. But today's figures, conveniently delayed until after the Conservative conference, are still stunningly bad. The service ran a deficit of £930m between April and June (greater than the £820m recorded for the whole of the 2014/15 financial year) and is on course for a shortfall of at least £2bn this year - its worst position for a generation. 

Though often described as having been shielded from austerity, owing to its ring-fenced budget, the NHS is enduring the toughest spending settlement in its history. Since 1950, health spending has grown at an average annual rate of 4 per cent, but over the last parliament it rose by just 0.5 per cent. An ageing population, rising treatment costs and the social care crisis all mean that the NHS has to run merely to stand still. The Tories have pledged to provide £10bn more for the service but this still leaves £20bn of efficiency savings required. 

Speculation is now turning to whether George Osborne will provide an emergency injection of funds in the Autumn Statement on 25 November. But the long-term question is whether anyone is prepared to offer a sustainable solution to the crisis. Health experts argue that only a rise in general taxation (income tax, VAT, national insurance), patient charges or a hypothecated "health tax" will secure the future of a universal, high-quality service. But the political taboo against increasing taxes on all but the richest means no politician has ventured into this territory. Shadow health secretary Heidi Alexander has today called for the government to "find money urgently to get through the coming winter months". But the bigger question is whether, under Jeremy Corbyn, Labour is prepared to go beyond sticking-plaster solutions. 

George Eaton is political editor of the New Statesman.