Anti‐transcription intermediary factor 1γ antibody titer correlates with clinical symptoms in a patient with recurrent dermatomyositis associated with ovarian cancer

A 42-year-old Japanese woman presented with erythema on the face and scattered erythematous lesions on the trunk. Histological findings taken from an erythema on the upper arm showed vacuolar change in basal keratinocytes and infiltration of lymphocytes around vessels in the upper dermis. The patient complained of muscle weakness in her upper arm. Serum examination revealed elevated levels of creatine phosphokinase (CPK: 500 IU/L). Anti-nuclear and anti-Jo1 antibodies were negative. She was diagnosed with dermatomyositis (DM). While screening the entire body for malignant growth, breast cancer (medullary carcinoma) was detected. The breast cancer was stage I (T1, N0, M0). Breast cancer resection and chemotherapy (cyclophosphamide, pirarubicin, 5-fluorouracil) were performed. Muscle weakness and skin lesions were resolved by the oral administration of prednisolone (40 mg/day). Prednisolone was tapered and was maintained at 2.5 mg/day. Eight years later, when the patient was 50 years old, she developed fever, progressive erythema on the face, trunk, limbs, and muscle weakness of the upper arm (Fig. 1a,b). Histological findings from the erythema on her chest showed the similar changes to those observed in the previous skin biopsy (Fig. 1c). Her cutaneous lesion was evaluated according to the Cutaneous Dermatomyositis Disease Area and Severity Index (CDASI)1 (Fig. 2). Laboratory results were as follows: aspartate aminotransferase 39 IU/L, lactate dehydrogenase 309 IU/L, CPK 232 IU/L and myoglobin 161 ng/mL. Given that the patient was diagnosed with the recurrence of DM, cancer screening was performed. The findings of 18F-fluorodeoxyglucose positron emission tomography computed tomography (FDG-PET-CT) showed an abnormal FDG-accumulation in the left ovary (Fig. 1d). Histopathological finding confirmed the presence of a serous cystadenocarcinoma of the ovary, Grade 3 at stage IIc (b) (T2c, N0, M0). After three courses of chemotherapy (TC therapy: paclitaxel and carboplatin) and a second debulking surgery (right salpingo-oophorectomy, omentectomy and pelvic lymph node dissection), no residual cancer tissues were detected. Oral administration of prednisolone (30 mg/day) was started, and when DM symptoms were improved, the dose was tapered to 5 mg/day. Anti-TIF1γ antibodies were measured over time by enzyme-linked immunosorbent assay system as previously described.2 The titer of anti-TIF1γ antibodies was elevated before the surgical resection of the ovarian cancer and then gradually decreased following chemotherapy (Fig. 2). Specifically, the anti-TIF1γ antibody titer correlated with the CDASI scores (Fig. 2). This result indicated that the anti-TIF1γ antibody titer implied the presence of cancer and correlated well with the clinical symptoms of DM. Since the treatments of both DM and ovarian cancer were performed at the same time, it remained unclear whether the anti-TIF1-γ titer correlated with the CPK levels. There are reports of DM cases showing correlation between clinical symptoms including malignancies and the levels of anti-TIF1γ antibody. Aggarwal et al.3 demonstrated that B cell depletion with rituximab in 200 patients with DM resulted in reduction of not only autoantibody levels, including anti-TIF1γ, but also disease activity. Taki et al.4 demonstrated that a young adult with DM, being comorbid with metastatic cancer, received chemotherapy, followed by a decrease of anti-TIF1γ levels and clinical improvement in DM and cancer. Our patient suffered from two independent cancers: first one was a breast cancer (medullary carcinoma) and the other was an ovarian cancer (serous cystadenocarcinoma), which developed 8 years later. Of note was that DM symptoms were faithfully associated with them. When DM recurs, any malignancy should be carefully examined even if one enjoys a long remission period after the first cancer. Recently, TIF1γ has been shown to act epigenetically as a tumor suppressor gene in hematopoietic cells, suggesting that tumor immunity might be associated with the development of DM.5 Interestingly, in our case, the serum anti-TIF1γ antibody titer was increased over time during the recurrence of DM, but it was decreased after surgical resection of ovarian cancer. These findings suggest that ovarian cancer may be closely related to production of anti-TIF1γ antibodies, which could be, therefore, a biomarker of cancer progression. TIF1γ overexpression has been demonstrated in highly progressive endometrial carcinoma in a patient with dermatomyositis positive for anti-TIF1γ antibody.6 Also, expression of the autoantigen TRIM33/TIF1γ in skin and muscle of DM patients may be upregulated, together with markers of cellular stress.7 We assumed that high expression of TIF1γ in malignant cells might induce the production of autoantigen to TIF1γ, although the underlying mechanism of development of DM was unknown. Moreover, we considered that both TIF1γ in the skin and muscle and autoantibodies might provoke inflammation. It is likely that anti-TIF1γ antibodies are not just biomarkers for DM patients harboring cancer, but are also associated with aberrant immune response in such patients. Collectively, our results indicate that anti-TIF1γ antibodies may be useful not only as biomarkers for DM, but also for the presence of malignancy. We have no funding sources and no conflict of interest disclosures.