[A case of mixed neuroendocrine-non-neuroendocrine neoplasm (MiNEN) diagnosed by re-biopsy of the enlarged primary tumor during chemotherapy for gastric adenocarcinoma].

Gastric mixed neuroendocrine-non-neuroendocrine neoplasm (MiNEN) is an extremely rare form of gastric neoplasm, and its prognosis is often poor. This is a case report wherein the primary site increased during chemotherapy against gastric adenocarcinoma and was diagnosed with gastric MiNEN after total gastrectomy. A 71-year-old man was diagnosed with gastric adenocarcinoma complicated with liver and para-aortic lymph node metastasis. Chemotherapy with S-1, oxaliplatin, and trastuzumab was initiated. Although the size of metastatic lesions was reduced after six courses of treatment, a part of the primary site of gastric tumor rapidly. Pathological rebiopsy of the primary site suggested a neuroendocrine carcinoma, and he was finally diagnosed with gastric MiNEN after total gastrectomy. Thus, second-line chemotherapy was then initiated showing good response. We herein report a case of MiNEN with a rare diagnostic process.

Identification of Novel HLA-A*24:02-Restricted Epitope Derived from a Homeobox Protein Expressed in Hematological Malignancies.

The homeobox protein, PEPP2 (RHOXF2), has been suggested as a cancer/testis (CT) antigen based on its expression pattern. However, the peptide epitope of PEPP2 that is recognized by cytotoxic T cells (CTLs) is unknown. In this study, we revealed that PEPP2 gene was highly expressed in myeloid leukemia cells and some other hematological malignancies. This gene was also expressed in leukemic stem-like cells. We next identified the first reported epitope peptide (PEPP2(271-279)). The CTLs induced by PEPP2(271-279) recognized PEPP2-positive target cells in an HLA-A*24:02-restricted manner. We also found that a demethylating agent, 5-aza-2'-deoxycytidine, could enhance PEPP2 expression in leukemia cells but not in blood mononuclear cells from healthy donors. The cytotoxic activity of anti-PEPP2 CTL against leukemic cells treated with 5-aza-2'-deoxycytidine was higher than that directed against untreated cells. These results suggest a clinical rationale that combined treatment with this novel antigen-specific immunotherapy together with demethylating agents might be effective in therapy-resistant myeloid leukemia patients.