Background/Purpose: Dermatomyositis is associated with an underlying malignancy in about 24% of cases. Anti-p155/140 antibodies have a strong predictive value for malignancy in adult dermatomyositis patients. The proposed target of the p155/140 antibodies are the TIF-1 family proteins, in particular TIF-1γ. Overexpression of TIF-1γ has been associated with the onset and progression of human hepatocellular carcinoma as well as with poor prognosis and worse survival in breast cancer, which suggests that it may play a role in carcinogenesis and represent a novel prognostic marker. We postulated that TIF-1γ was overexpressed in the duodenal adenocarcinoma of a patient with p155/140 dermatomyositis.  

Methods: The patient’s intestinal mass was processed following standard protocols for clinical examination and staging of intestinal cancer. After the primary diagnosis was made, formalin/PFA-fixed paraffin-embedded tissue blocks representative of the adenocarcinoma, adjacent normal small intestinal mucosa, as well as small intestinal adenocarcinoma tissue from a patient without dermatomyositis were selected for immunohistochemical staining with an anti-TIF-1γ mouse monoclonal primary antibody (Abcam Inc. Catalog nr. ab57172).  

Results: The non-neoplastic small intestinal mucosa (figure 1) adjacent to the tumor showed an expected pattern of staining, with faint nuclear positivity in the regenerating cells of the crypts. The tumor cells (figure 2), however, showed strong diffuse nuclear staining, consistent with high levels of TIF-1γ.  The small intestine adenocarcinoma from a patient without dermatomyositis also showed strong diffuse nuclear positivity.  

Conclusion: We present the first evidence to our knowledge of TIF-1 overexpression in a solid tissue malignancy from a patient with anti-TIF-1γ (anti-p155/140) dermatomyositis. TIF-1γ was markedly overexpressed in the adenocarcinoma tissue from both the patient with p155/140 dermatomyositis and the patient without dermatomyositis, but showed only faint nuclear expression in the healthy intestinal tissue. The most intriguing question remains why TIF-1γ overexpression in malignant cells does not lead to an autoimmune response in each case and whether genetic alterations in the TRIM33 locus may render TIF-1γ immunogenic in a specific subset of patients.