Department of Pathology, West China Hospital, Sichuan University, Chengdu, 610041, China.
Department of Pathology, The Second People's Hospital of Yibin, Yibin, 644000, China.
J Cancer Res Clin Oncol. 2023 Aug;149(9):6361-6370. doi: 10.1007/s00432-023-04621-5. Epub 2023 Feb 8.
Nuclear protein in testis (NUT) carcinoma is an uncommon malignant cancer characterized by NUTM1 rearrangement. We aimed to investigate the clinicopathological and molecular features and immunotherapy of pulmonary NUT carcinoma.
Immunohistochemistry (IHC) for NUT (C52B1) and programmed cell death ligand 1 (PD-L1: 22C3) and fluorescence in situ hybridization (FISH) for NUTM1 break and BRD4-NUTM1 fusion were performed on six pulmonary NUT carcinoma samples.
The 6 pulmonary NUT carcinoma samples were obtained from 5 males and 1 female, with ages ranging from 31 to 73 years (average, 46 years). Five tumors occurred in the lobes, with one in the trachea. Pathologically, all cases showed primitive-appearing round to epithelioid cells growing in nests and sheets. Squamous differentiation and abrupt keratinization were observed. All tumors expressed the NUT protein and p63, and 4 tumors showed focal synaptophysin, but PD-L1 expression was not observed. All cases displayed NUTM1 rearrangement, 5 had BRD4-NUTM1 fusion, and one had an unknown partner. Three patients presented regional lymph node involvement at diagnosis. Five patients underwent intensive radiation and/or chemotherapy. Furthermore, 2 patients (1 and 2) received a combination of PD-L1 inhibitor and chemotherapy. Patient 1 exhibited a poor response and soon showed tumor progression and metastasis; however, patient 2 responded remarkably and achieved pathologic complete response (pCR) without uncontrollable adverse events. The overall survival time was 2.9 months.
Pulmonary NUT carcinoma exhibits poorly differentiated morphological features with diffuse NUT staining, low PD-L1 expression, and NUTM1 rearrangement. Despite its poor prognosis, it presents a diverse response to immunotherapy. Immune checkpoint inhibitors (ICIs) need to be further explored in NUT carcinoma.
睾丸核蛋白（NUT）癌是一种罕见的恶性肿瘤，其特征是 NUTM1 重排。本研究旨在探讨肺 NUT 癌的临床病理和分子特征及免疫治疗。
对 6 例肺 NUT 癌标本进行 NUT（C52B1）和程序性细胞死亡配体 1（PD-L1：22C3）免疫组化（IHC）及 NUTM1 断裂和 BRD4-NUTM1 融合的荧光原位杂交（FISH）检测。
6 例肺 NUT 癌标本取自 5 例男性和 1 例女性，年龄 31～73 岁，平均 46 岁。5 例肿瘤发生于肺叶，1 例发生于气管。病理上，所有肿瘤均表现为原始形态的圆形至上皮样细胞巢状和片状生长，伴有鳞状分化和突然角化。所有肿瘤均表达 NUT 蛋白和 p63，4 例肿瘤显示局灶性突触素表达，但未观察到 PD-L1 表达。所有病例均显示 NUTM1 重排，5 例存在 BRD4-NUTM1 融合，1 例存在未知融合伴侣。3 例患者诊断时存在区域淋巴结受累。5 例患者接受了强化放疗和/或化疗。此外，2 例患者（1 号和 2 号）接受了 PD-L1 抑制剂联合化疗。1 号患者反应较差，很快出现肿瘤进展和转移；而 2 号患者反应显著，达到病理完全缓解（pCR），且无不可控的不良反应。总生存时间为 2.9 个月。
肺 NUT 癌表现为形态学分化差，弥漫性 NUT 染色，低 PD-L1 表达和 NUTM1 重排。尽管预后较差，但对免疫治疗有不同的反应。免疫检查点抑制剂（ICI）需要在 NUT 癌中进一步探索。
