Precision histology: how deep learning is poised to revitalize histomorphology for personalized cancer care.
Precision histology: how deep learning is poised to revitalize histomorphology for personalized cancer care.
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DOI：
10.1038/s41698-017-0022-1
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发表时间：
2017
影响因子：
7.9
通讯作者：
Diamandis P
中科院分区：
文献类型：
--
作者：
Djuric U;Zadeh G;Aldape K;Diamandis P
一个多世纪以来，对苏木精伊红(H&E)玻片的准确解释一直是病理分析和诊断医学的基础。1对于病理学家来说，H&E幻灯片相当于高质量的病历或体检。它结合了艺术和科学，以帮助分类和指导更有针对性和专业化的辅助研究。不幸的是，近年来，由于更多当代和数据丰富的分子研究的出现，组织形态分析在精确医学时代的感知价值正在减少。2-4具有讽刺意味的是，鉴于广泛可用的全身成像技术，这与患者病史和体检面临的审查没有什么不同。5-7一些人甚至提出，鉴于测序成本呈指数级下降，医学评估可以有效地从全基因组分析开始。8在这里，我们通过强调H&E污点的一些优点和缺点来讨论它的现状和可能的未来。很可能，近年来H&E显微镜检查面临的审查不是它自己的错，而是缺乏有效的方法来常规地提取它所包含的更多丰富的形态信息。对于病理学家和临床医生来说，H&E幻灯片仍然是一个有价值的工具。例如，外科医生经常要求紧急的术中病理解释来帮助指导手术。这种临床情况通常需要在5-10分钟内做出准确的诊断。结果通常对剩余手术的轨迹有很大的影响(例如，切除的范围，对额外的实验室检查进行分类)。因此，大多数外科医生强烈倾向于高度专业化的病理学家的专家意见(例如，神经外科手术中咨询的神经病理学家的意见)。在分子或替代分析方法与这些紧迫的时间框架兼容之前，H&E幻灯片将继续是帮助指导外科护理的基本工具。H&E幻灯片在亚急性环境下的精确肿瘤学中也发挥着关键作用。现在，技术进步使患者的肿瘤可以在基因组、表观基因组、转录组、蛋白质组、磷蛋白质组和其他基因组水平上进行全球分析。3、9、10这份分子测试清单，每一项都有自己的长处和短处，还在继续增长。然而，即使测序成本下降，在可预见的未来，对每个样本进行常规的多平台分子分析可能也不会成为一种具有时效性或成本效益的策略。这种相对较高的多组体分析成本将继续需要分子分选，以帮助将测试范围缩小到最适合特定肿瘤类型和临床情景的测试。最后，当只有极少量的组织不足以进行分子分析时，H&E玻片仍然是最通用的诊断工具之一。同样，与基于大块组织的分子测试不同，显微分析保留了重要的区域到区域、单细胞水平的空间信息，这些信息可能对诊断和治疗决策具有重大影响。11、12例如，即使对于已经在分子水平上进行了分析的肿瘤，当注意到特定的显微特征(例如，淋巴血管侵犯、转移灶、核分裂活性升高、肿瘤形态13)时，治疗方案也会发生巨大的变化。14因此，在我们日益增长的精确肿瘤学工具箱中，有许多令人信服的理由保留H&E检查作为一种不重叠的和基本的工具。也许H&E幻灯片在“大数据”时代的一个主要限制是没有辅助的人类…。
Accurate interpretation of the hematoxylin and eosin (H&E) slide has remained the foundation of pathological analysis and diagnostic medicine for over a century. 1 For the pathologist, the H&E slide is equivalent to a high-quality patient history or physical exam. It combines art and science to help triage and guide more focused and specialized ancillary studies. Unfortunately, the perceived value of histomorphologic analysis in the era of precision medicine is diminishing in recent years due to the emergence of more contemporary and data-rich molecular studies. 2–4 Ironically, this is no different than the scrutiny that the patient history and physical exam have faced, in light of widely available whole-body imaging technologies. 5–7 Some have even proposed that given the exponential decrease in sequencing costs, medical assessment could effectively begin with wholegenome analysis. 8 Here, we discuss the current state and the possible future of the H&E stain by highlighting some of its strengths and shortcomings. It may well be that the scrutiny that the H&E microscopic exam has faced in recent years 4 is no fault of its own, but the lack of effective approaches to routinely extract more of the rich morphologic information it contains. The H&E slide continues to be a valuable tool for pathologists and clinicians alike. For example, quite often, surgeons request urgent intra-operative pathological interpretations to help guide surgery. This clinical scenario often necessitates that an accurate diagnosis be rendered within 5–10 min. The outcome usually has huge implications for the trajectory of the remaining surgery (eg, extent of resection, triaging additional laboratory tests). As a result, most surgeons have a strong preference for the expert opinion of highly subspecialized pathologists (eg, from a neuropathologist for neurosurgical intra-operative consults). Until molecular or alternative analytic approaches become compatible with these acute timeframes, the H&E slide will continue to be an essential tool to help guide surgical care. The H&E slide also has a key role in precision oncology in subacute settings. Technological advances now allow patients’ tumors to be globally profiled at the genomic, epigenomic, transcriptomic, proteomic, phosphoproteomic, and other-omic levels. 3, 9, 10 This list of molecular tests, each with their own strengths and weaknesses, continues to grow. However, even with decreasing costs of sequencing, performing routine multi-platform molecular analysis on every specimen will likely not become a time-effective or cost-effective strategy in the foreseeable future. This relatively high cost of multi-omic analysis will continue to necessitate molecular triaging to help narrow testing to those most appropriate for the specific tumor type and clinical scenario. Lastly, the H&E slide still remains one of the most versatile diagnostic tools when only minute amounts of tissue, insufficient for molecular analysis, is available. Similarly, unlike bulk tissuebased molecular tests, microscopic analysis preserves important region-to-region, single-cell-level spatial information that may have significant implications for diagnostic and treatment decisions. 11, 12 For example, even for tumors that have been analyzed at the molecular level, treatment regimens can dramatically change when specific microscopic features are noted (eg, lymphovascular invasion, metastatic foci, elevated mitotic activity, 13 tumor morphology). 14 Therefore, there are many compelling reasons to retain the H&E exam as a nonoverlapping and essential tool in our growing precision oncology toolbox.Perhaps a major limitation of the H&E slide in the era of “bigdata” is the unassisted human …
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DOI：
10.1109/tbme.2011.2110648
发表时间：
2011-07
期刊：
IEEE transactions on bio-medical engineering
影响因子：
--
作者：
Dundar MM;Badve S;Bilgin G;Raykar V;Jain R;Sertel O;Gurcan MN
通讯作者：
Gurcan MN
影响因子：
12.7
作者：
Fossati, G;Ricevuti, G;Rossi, ML
通讯作者：
Rossi, ML
影响因子：
7.7
作者：
Kothari S;Phan JH;Stokes TH;Osunkoya AO;Young AN;Wang MD
通讯作者：
Wang MD
影响因子：
64.8
作者：
Esteva A;Kuprel B;Novoa RA;Ko J;Swetter SM;Blau HM;Thrun S
通讯作者：
Thrun S
DOI：
10.1056/nejmoa1402121
发表时间：
2015-06-25
期刊：
The New England journal of medicine
影响因子：
--
作者：
Cancer Genome Atlas Research Network;Brat DJ;Verhaak RG;Aldape KD;Yung WK;Salama SR;Cooper LA;Rheinbay E;Miller CR;Vitucci M;Morozova O;Robertson AG;Noushmehr H;Laird PW;Cherniack AD;Akbani R;Huse JT;Ciriello G;Poisson LM;Barnholtz-Sloan JS;Berger MS;Brennan C;Colen RR;Colman H;Flanders AE;Giannini C;Grifford M;Iavarone A;Jain R;Joseph I;Kim J;Kasaian K;Mikkelsen T;Murray BA;O'Neill BP;Pachter L;Parsons DW;Sougnez C;Sulman EP;Vandenberg SR;Van Meir EG;von Deimling A;Zhang H;Crain D;Lau K;Mallery D;Morris S;Paulauskis J;Penny R;Shelton T;Sherman M;Yena P;Black A;Bowen J;Dicostanzo K;Gastier-Foster J;Leraas KM;Lichtenberg TM;Pierson CR;Ramirez NC;Taylor C;Weaver S;Wise L;Zmuda E;Davidsen T;Demchok JA;Eley G;Ferguson ML;Hutter CM;Mills Shaw KR;Ozenberger BA;Sheth M;Sofia HJ;Tarnuzzer R;Wang Z;Yang L;Zenklusen JC;Ayala B;Baboud J;Chudamani S;Jensen MA;Liu J;Pihl T;Raman R;Wan Y;Wu Y;Ally A;Auman JT;Balasundaram M;Balu S;Baylin SB;Beroukhim R;Bootwalla MS;Bowlby R;Bristow CA;Brooks D;Butterfield Y;Carlsen R;Carter S;Chin L;Chu A;Chuah E;Cibulskis K;Clarke A;Coetzee SG;Dhalla N;Fennell T;Fisher S;Gabriel S;Getz G;Gibbs R;Guin R;Hadjipanayis A;Hayes DN;Hinoue T;Hoadley K;Holt RA;Hoyle AP;Jefferys SR;Jones S;Jones CD;Kucherlapati R;Lai PH;Lander E;Lee S;Lichtenstein L;Ma Y;Maglinte DT;Mahadeshwar HS;Marra MA;Mayo M;Meng S;Meyerson ML;Mieczkowski PA;Moore RA;Mose LE;Mungall AJ;Pantazi A;Parfenov M;Park PJ;Parker JS;Perou CM;Protopopov A;Ren X;Roach J;Sabedot TS;Schein J;Schumacher SE;Seidman JG;Seth S;Shen H;Simons JV;Sipahimalani P;Soloway MG;Song X;Sun H;Tabak B;Tam A;Tan D;Tang J;Thiessen N;Triche T Jr;Van Den Berg DJ;Veluvolu U;Waring S;Weisenberger DJ;Wilkerson MD;Wong T;Wu J;Xi L;Xu AW;Yang L;Zack TI;Zhang J;Aksoy BA;Arachchi H;Benz C;Bernard B;Carlin D;Cho J;DiCara D;Frazer S;Fuller GN;Gao J;Gehlenborg N;Haussler D;Heiman DI;Iype L;Jacobsen A;Ju Z;Katzman S;Kim H;Knijnenburg T;Kreisberg RB;Lawrence MS;Lee W;Leinonen K;Lin P;Ling S;Liu W;Liu Y;Liu Y;Lu Y;Mills G;Ng S;Noble MS;Paull E;Rao A;Reynolds S;Saksena G;Sanborn Z;Sander C;Schultz N;Senbabaoglu Y;Shen R;Shmulevich I;Sinha R;Stuart J;Sumer SO;Sun Y;Tasman N;Taylor BS;Voet D;Weinhold N;Weinstein JN;Yang D;Yoshihara K;Zheng S;Zhang W;Zou L;Abel T;Sadeghi S;Cohen ML;Eschbacher J;Hattab EM;Raghunathan A;Schniederjan MJ;Aziz D;Barnett G;Barrett W;Bigner DD;Boice L;Brewer C;Calatozzolo C;Campos B;Carlotti CG Jr;Chan TA;Cuppini L;Curley E;Cuzzubbo S;Devine K;DiMeco F;Duell R;Elder JB;Fehrenbach A;Finocchiaro G;Friedman W;Fulop J;Gardner J;Hermes B;Herold-Mende C;Jungk C;Kendler A;Lehman NL;Lipp E;Liu O;Mandt R;McGraw M;Mclendon R;McPherson C;Neder L;Nguyen P;Noss A;Nunziata R;Ostrom QT;Palmer C;Perin A;Pollo B;Potapov A;Potapova O;Rathmell WK;Rotin D;Scarpace L;Schilero C;Senecal K;Shimmel K;Shurkhay V;Sifri S;Singh R;Sloan AE;Smolenski K;Staugaitis SM;Steele R;Thorne L;Tirapelli DP;Unterberg A;Vallurupalli M;Wang Y;Warnick R;Williams F;Wolinsky Y;Bell S;Rosenberg M;Stewart C;Huang F;Grimsby JL;Radenbaugh AJ;Zhang J
通讯作者：
Zhang J