POU2F3 in SCLC: Clinicopathologic and Genomic Analysis With a Focus on Its Diagnostic Utility in Neuroendocrine-Low SCLC.
POU2F3 in SCLC: Clinicopathologic and Genomic Analysis With a Focus on Its Diagnostic Utility in Neuroendocrine-Low SCLC.
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DOI：
10.1016/j.jtho.2022.06.004
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发表时间：
2022-09
影响因子：
20.4
通讯作者：
Rekhtman, Natasha
中科院分区：
文献类型：
--
作者：
Baine, Marina K.;Febres-Aldana, Christopher A.;Chang, Jason C.;Jungbluth, Achim A.;Sethi, Shenon;Antonescu, Cristina R.;Travis, William D.;Hsieh, Min-Shu;Roh, Mee Sook;Homer, Robert J.;Ladanyi, Marc;Egger, Jacklynn V.;Lai, W. Victoria;Rudin, Charles M.;Rekhtman, Natasha
POU2F3是一种与化学感觉簇状细胞(SCLC-P)相关的小细胞肺癌(SCLC)亚型的最新标志物。SCLC-P的特性尚未完全确定，有关POU2F3在其他肺部肿瘤中表达的数据也很少。我们筛选了254例小细胞癌POU2F3的表达，并综合分析了POU2F3阳性肿瘤的组织病理学、基因组和临床特征。我们还研究了POU2F3在其他主要肺癌类型中的表达(n=433)和一组潜在的小细胞肺癌诊断模拟物(n=123)。POU2F3在254例小细胞肺癌中表达30例(12%)，且与标准神经内分泌标记物(突触素、嗜铬粒素A、CD56、INSM1)的低表达密切相关。值得注意的是，POU2F3在神经内分泌标志物完全阴性或极少量表达的小细胞肺癌中的表达占75%(n=20)，有助于此类病例的小细胞肺癌诊断。广泛靶向下一代测序显示，SCLC-P(n=12)在几个改变中表现出丰富，包括PTEN失活、MYC扩增和20q13扩增，但RB1和TP53改变的比率与其他小细胞肺癌(n=155)相似。除小细胞肺癌外，POU2F3仅在大细胞神经内分泌癌(12%)和基底细胞样鳞癌(22%)中表达。这是迄今为止最大的SCLC-P临床样本队列，我们描述了POU2F3在标准神经内分泌标志物低表达或缺乏表达的具有挑战性的SCLC亚组中的诊断作用。SCLC-P独特的基因组改变可能为治疗靶向提供新的途径。POU2F3在其他肺癌类型的一小部分中的作用值得进一步研究。
POU2F3 is a recent marker of a small cell lung carcinoma (SCLC) subtype related to chemosensory tuft cells (SCLC-P). The characteristics of SCLC-P have not been fully defined, and the data on POU2F3 expression in other lung tumors are scarce. We screened 254 SCLC for POU2F3 expression, and comprehensively analyzed histopathologic, genomic, and clinical characteristics of POU2F3-positive tumors. We also explored POU2F3 expression in other major lung cancer types (n=433) and a targeted set of potential diagnostic mimics of SCLC (n=123). POU2F3 was expressed in 30 of 254 (12%) SCLC, and was strongly associated with low expression of standard neuroendocrine markers (synaptophysin, chromogranin A, CD56, INSM1). Notably, POU2F3 was expressed in 75% of SCLC with entirely negative or minimal neuroendocrine marker expression (n=20) and was helpful in supporting the diagnosis of SCLC in such cases. Broad targeted next-generation sequencing revealed that SCLC-P (n=12) exhibited enrichment in several alterations, including PTEN inactivation, MYC amplifications, and 20q13 amplifications, but similar rates of RB1 and TP53 alterations as other SCLC (n=155). Beyond SCLC, POU2F3 expression was exclusively limited to large cell neuroendocrine carcinoma (12%) and basaloid squamous cell carcinoma (22%). This is the largest cohort of SCLC-P clinical samples to-date, where we describe the diagnostic utility of POU2F3 in a challenging subset of SCLC with low or absent expression of standard neuroendocrine markers. The distinct genomic alterations in SCLC-P may offer a novel avenue for therapeutic targeting. The role of POU2F3 in a narrow subset of other lung cancer types warrants further study.
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影响因子：
11.2
作者：
Laddha, Saurabh V.;da Silva, Edaise M.;Chan, Chang S.
通讯作者：
Chan, Chang S.
影响因子：
16.6
作者：
George J;Walter V;Peifer M;Alexandrov LB;Seidel D;Leenders F;Maas L;Müller C;Dahmen I;Delhomme TM;Ardin M;Leblay N;Byrnes G;Sun R;De Reynies A;McLeer-Florin A;Bosco G;Malchers F;Menon R;Altmüller J;Becker C;Nürnberg P;Achter V;Lang U;Schneider PM;Bogus M;Soloway MG;Wilkerson MD;Cun Y;McKay JD;Moro-Sibilot D;Brambilla CG;Lantuejoul S;Lemaitre N;Soltermann A;Weder W;Tischler V;Brustugun OT;Lund-Iversen M;Helland Å;Solberg S;Ansén S;Wright G;Solomon B;Roz L;Pastorino U;Petersen I;Clement JH;Sänger J;Wolf J;Vingron M;Zander T;Perner S;Travis WD;Haas SA;Olivier M;Foll M;Büttner R;Hayes DN;Brambilla E;Fernandez-Cuesta L;Thomas RK
通讯作者：
Thomas RK
影响因子：
16.6
作者：
Dammed, Marcel A.;Bragelmann, Johannes;Sos, Martin L.
通讯作者：
Sos, Martin L.
影响因子：
64.8
作者：
Montoro DT;Haber AL;Biton M;Vinarsky V;Lin B;Birket SE;Yuan F;Chen S;Leung HM;Villoria J;Rogel N;Burgin G;Tsankov AM;Waghray A;Slyper M;Waldman J;Nguyen L;Dionne D;Rozenblatt-Rosen O;Tata PR;Mou H;Shivaraju M;Bihler H;Mense M;Tearney GJ;Rowe SM;Engelhardt JF;Regev A;Rajagopal J
通讯作者：
Rajagopal J
DOI：
10.1097/pas.0b013e3181aa30a5
发表时间：
2009-09
期刊：
The American journal of surgical pathology
影响因子：
--
作者：
Busam KJ;Jungbluth AA;Rekthman N;Coit D;Pulitzer M;Bini J;Arora R;Hanson NC;Tassello JA;Frosina D;Moore P;Chang Y
通讯作者：
Chang Y