Cancer could act as possible trigger of MuSK-MG in some cases: Study
Higher likelihood of prior cancer found in late-onset MuSK-MG
A recent study has reported a potential connection between cancer development and a subtype of myasthenia gravis (MG).
The study, conducted in Italy, revealed the presence of muscle-specific kinase (MuSK) protein in tumor samples from patients with MuSK myasthenia gravis (MuSK-MG). The data also indicated a higher likelihood of a prior cancer diagnosis in patients whose MuSK-MG onset occurred after the age of 51.
The relationship between autoimmunity and cancer is bidirectional, as immunosuppression associated with autoimmune treatment may increase cancer risk, while the immune response against tumors may potentially lead to autoimmune disease.
“Assessing cancer frequency among MG patients is particularly relevant given the emergence of novel molecular therapies avoiding immune system suppression,” researchers wrote.
The data was reported in the article “Cancer Frequency in MuSK Myasthenia Gravis and Histological Evidence of Paraneoplastic Etiology,” which was published in the journal Annals of Neurology.
5% to 7% of MG patients have autoantibodies against MuSK receptor
An estimated 5% to 7% of MG patients have autoantibodies against the MuSK receptor. This protein receptor is involved in the formation and maintenance of the neuromuscular junction, that is, the connection between motor nerves and muscles.
The prevalence of cancer in MuSK-MG patients is still unknown. There are also no documented cases of patients developing MuSK-MG as a result of having had cancer previously, a situation known as paraneoplastic syndrome.
To explain these potential connections between cancer and MuSK-MG, a retrospective study was conducted by researchers in Italy, based on the review of medical records between 2005 and 2022. The study included data from patients diagnosed with MuSK-MG and with at least one year of follow-up. The development of cancer and the timing of its diagnosis in relation to MuSK-MG onset were analyzed.
In total, 94 MuSK-MG patients, with 73 being women (78% of the group), with a median age of 51 years at MuSK-MG onset, were included in the study. Fifteen cancers were reported in 13 patients, yielding a prevalence of 13.8%. The median age at cancer diagnosis was 64 years.
The most common cancer type was hematologic, diagnosed in five patients before MG onset. Other malignancies included three breast cancers, two uterine cancers, two digestive organ cancers, and one each of lung, vocal cord, and skin cancer.
Cancer was diagnosed before MuSK-MG onset in five patients, concurrently during the period analyzed in two patients, and after MuSK-MG onset in eight patients.
From two patients who developed MuSK-MG after their cancer was diagnosed, samples of tumor tissue were analyzed for the presence of MuSK protein. In total, six tissue samples were evaluated, three from a patient with primary mediastinal large B-cell lymphoma (PMBCL) and the other three from a patient with clear cell endometrial carcinoma (ECCC).
MuSK presence found in cancer cells of some patients
The samples showed MuSK presence in cancer cells of PMBCL and ECCC from the two MuSK-MG patients. In samples from patients without a subsequent MuSK-MG diagnosis, MuSK expression was also found in two PMBCLs and one ECCC.
MuSK is a protein that acts as a receptor and is normally found on cell surfaces, where it signals external cues to direct cellular functions. In the patient tumor samples, MuSK was observed more abundantly inside cancer cells, specifically in the nucleus, indicating a likely functional change. Mutations, excessive production, and improper signaling of this kind of receptor can lead to disease development, including cancer.
“The demonstration of MuSK nuclear immunoreactivity in patients’ tumors supports a possible paraneoplastic etiology for some MuSK-MG cases,” the researchers wrote, suggesting “MuSK expression in cancer cells may initiate MuSK autoantibody production.” This, consequently, may induce MuSK-MG, indicating a possible mechanism in which cancer acts as a trigger for the development of MuSK-MG.
Patients with MuSK-MG and a cancer diagnosis were a median age of 59 years, which was significantly older than the median age of 41 years for MuSK-MG patients without cancer. The total patient population was then divided into two groups: younger or older than 51. The relationship between different patient conditions and cancer presence was evaluated.
The analysis indicated a higher likelihood of underlying cancer in patients whose MuSK-MG onset occurred after the age of 51.
“This finding may suggest the need for a tailored cancer screening protocol in this MuSK-MG population,” the researchers wrote.
Overall, the study results point toward the existence of a connection between increased MuSK expression in tumors and the production of autoantibodies directed against MuSK, which may lead to a late onset of MuSK-MG.
However, more studies are needed to explore the possible paraneoplastic origin of MuSK-MG, the team concluded.
About the Author
