A novel Tn antigen epitope‑recognizing antibody for MUC1 predicts clinical outcome in patients with primary lung adenocarcinoma

Kato,Tatsuya; Ujiie,Hideki; Hatanaka,Kanako C.; Nange,Ayae; Okumura,Asami; Tsubame,Kaho; Naruchi,Kentato; Sato,Masaharu; Kaga,Kichizo; Matsuno,Yoshihiro; Wakasa,Satoru; Hatanaka,Yutaka

doi:10.3892/ol.2021.12463

A novel Tn antigen epitope‑recognizing antibody for MUC1 predicts clinical outcome in patients with primary lung adenocarcinoma

Authors:
- Tatsuya Kato
- Hideki Ujiie
- Kanako C. Hatanaka
- Ayae Nange
- Asami Okumura
- Kaho Tsubame
- Kentato Naruchi
- Masaharu Sato
- Kichizo Kaga
- Yoshihiro Matsuno
- Satoru Wakasa
- Yutaka Hatanaka
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Affiliations: Department of Cardiovascular and Thoracic Surgery, Hokkaido University Faculty and School of Medicine, Sapporo, Hokkaido 060‑8638, Japan, Clinical Research and Medical Innovation Center, Hokkaido University Hospital, Sapporo, Hokkaido, 060‑8648, Japan, Research Division of Companion Diagnostics, Hokkaido University Hospital, Sapporo, Hokkaido, 060‑8648, Japan, Department of Pathology, Hokkaido University Graduate School of Medicine, Sapporo, Hokkaido 060‑8638, Japan, Medicinal Chemistry Pharmaceuticals, Co., Ltd., Sapporo, Hokkaido 060‑0009, Japan, Department of Surgical Pathology, Hokkaido University Hospital, Sapporo, Hokkaido 060‑8648, Japan
Published online on: January 12, 2021 https://doi.org/10.3892/ol.2021.12463
Article Number: 202

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Abstract

Mucin 1 (MUC1) expression is upregulated in multiple types of cancer, including lung cancer. However, the conventional anti‑MUC1 antibody is not useful for the differentiation of malignant lung tumors and benign lesions due to its limited specificity. Our previous study screened a novel epitope‑defined antibody against cancer‑associated sugar chain structures that specifically recognizes the MUC1 Tn antigen (MUC1‑Tn ED Ab). In the present study, its potential utility as a diagnostic marker and therapeutic tool for lung adenocarcinoma (ADC) was examined. Immunohistochemical analysis of a lung ADC tissue microarray was performed using the MUC1‑Tn ED Ab (clone SN‑102), and the results were compared with those of another clone and commercially available MUC1 antibodies. The association between positive immunoreactivity of SN‑102 and clinicopathologic factors was analyzed. Furthermore, the association between MUC1‑Tn expression and epithelial‑mesenchymal transition markers and radiological characteristics was analyzed. Moderate or high MUC1‑Tn expression (MUC1‑Tn‑H) was observed in 138 (78.9%) of the 175 lung ADC cases. MUC1‑Tn‑H was associated with male sex, cigarette smoking, tumor extension, pleural invasion, and higher preoperative serum carcinoembryonic antigen and cytokeratin 19 fragment levels. Tumors with MUC1‑Tn‑H had higher consolidation/tumor ratios according to computed tomography and greater uptakes of 18F‑fluorodeoxyglucose. A total of 46 (26.9%) of the tumors had mesenchymal features, and MUC1‑Tn positivity was higher in the mesenchymal group than in the epithelial and intermediate groups (P<0.01 and P<0.01, respectively). Patients with tumors exhibiting MUC1‑Tn‑H had significantly shorter 5‑year overall and disease‑free survival times (P=0.011 and P<0.001, respectively). Additionally, MUC1‑Tn‑H was identified as an independent prognostic factor in multivariate analysis (P=0.024). MUC1‑Tn is specific for lung cancer cells and can improve diagnostic capabilities. Additionally, it may be a potential therapeutic target in lung ADC.

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