首页 我的

转载 乳腺癌病理学评估 NCCN2016v1

张品良 副主任医师 山东省肿瘤医院 呼吸肿瘤内科
2016-03-24 322人已读
张品良 副主任医师
山东省肿瘤医院

NCCN Guidelines Version 1.2016 NCCN指南2016年第1版

Breast Cancer
乳腺癌山东省肿瘤医院呼吸肿瘤内科张品良

Pathology Assessment
病理学评估

A central component of the treatment of breast cancer is full knowledge of extent of disease and biologic features. These factors contribute to the determination of the stage of disease, assist in the estimation of the risk that the cancer will recur, and provide information that predicts response to therapy (eg, estrogen receptor [ER], progesterone receptor [PR], human epidermal growth factor receptor 2 [HER2]). These factors are determined by examination of excised tissue and are provided in a written pathology report. Accurate pathology reporting requires communication between the clinician and the pathologist relating to relevant patient history, prior breast biopsies, prior irradiation to the chest, pregnancy status, characteristics of the abnormality biopsied (eg, palpable, mammographically detected microcalcifications), clinical state of lymph nodes, presence of inflammatory change or other skin abnormality, and any prior treatment administered (eg, chemotherapy, radiation therapy). The specimens should be oriented for the pathologist, and specific requests for determination of biomarkers should be stated (eg, ER, PR, and HER2 status). The use of consistent, unambiguous standards for reporting is strongly encouraged. Data from both national and local surveys show that as many as 50% of pathology reports for breast cancer are missing some elements critical to patient management. Significant omissions include failure to orient and report surgical margins and failure to report tumor grade consistently.
乳腺癌治疗的一个最重要的部分是对病变范围与生物学特征的充分认识。这些因素有助于确定疾病的分期、帮助判断癌症复发的风险以及提供预测治疗应答的信息(例如雌激素受体[ER]、孕激素受体[PR]、人类表皮生长因子受体2[HER2])。这些因素通过检查切除的组织确定并以书面病理学报告的方式提供。准确的病理学报告需要临床医师与病理学家之间交流相应患者的信息:病史、既往乳腺活检、既往胸部照射、妊娠情况、该异常活检的特点(如可触知、乳房摄影检出微小钙化)、临床上淋巴结情况、存在炎性改变或其它的皮肤异常以及既往给予的任何治疗(例如化疗、放疗)。应该为病理学家定位标本,且应当说明生物标志物测定的具体要求(例如ER、PR和HER2状态)。强烈鼓励使用一致、明确的报告标准。来自国家与地方的调查数据均显示多达50%的乳腺癌病理报告缺乏病人管理的某些关键因素。重要的遗漏包括没有定位并记录手术切缘以及没有坚持记录肿瘤分级。

The College of American Pathologists (CAP) has developed pathology reporting protocols to promote complete and standardized reporting of malignant specimens. CAP provides a protocol for each disease site that includes cancer case summaries (checklists) along with background documentation. These checklists form the basis for a synoptic, standardized reporting of pathologic findings. The checklists are available without charge through the CAP website at www.cap.org. Consistent, unambiguous, and complete pathology reporting is a cornerstone of quality breast cancer care, and the NCCN Breast Cancer Panel endorses the use of the CAP protocols for reporting the pathologic analysis of all breast cancer specimens.
为促进完善并统一恶性标本的报告美国病理医师学会(CAP)已经开发出了病理报告协议。CAP为每一疾病部位都提供了一个协议流程即包括癌症病例摘要(清单)以及背景资料记录。这些清单构成摘要、病理结果标准化报告的基础。清单可从CAP网址www.cap.org.免费获得。一致、明确且完善的病理学报告是乳腺癌管理质量的基石,NCCN乳腺癌小组支持对所有的乳腺癌标本使用CAP病理检查报告协议。

ER status should be determined for all samples of ductal carcinoma in situ (DCIS), and ER and PR tumor status should be determined for all samples of invasive breast cancer. ER and PR tumor status is normally determined by immunohistochemistry (IHC) testing. Although this method is considered reliable when performed by experienced pathology personnel, there have been several reports indicating that the reliability of ER and PR determinations can vary widely from one laboratory to another. These inter-laboratory differences may be attributable to the diverse methodologies and diverse interpretation schema used to evaluate tumor hormonal status. An NCCN Task Force and a panel of ASCO and CAP members have reviewed this topic and issued recommendations on ER and PR testing in breast cancer. Breast cancers that have at least 1% of cells staining positive for ER should be considered ER-positive.
对于所有的导管原位癌(DCIS)标本均应该测定ER状态,对于所有的侵袭性乳腺癌标本均应该测定肿瘤ER和PR状态。肿瘤ER和PR状态通常用免疫组化(IHC)检测测定。尽管当由有经验的病理学人员完成时该方法被认为是可靠的,但是已有若干报告提示ER和PR测定的可靠性从一个实验室到另一个实验室可以变化很大。这些实验室之间的差异也许可归因于评估肿瘤激素状态所使用的方法与判读模式各种各样。NCCN工作组与ASCO小组以及CAP成员已经综述了乳腺癌ER与PR检测课题与推荐的论点。至少有1%的细胞ER染色阳性的乳腺癌应该考虑ER阳性。

Principles of HER2 Testing
HER2检测原则

Along with ER and PR, the determination of HER2 tumor status is recommended for all newly diagnosed invasive breast cancers and for first recurrences of breast cancer whenever possible. The NCCN Breast Cancer Panel endorses CAP accreditation for anatomic pathology laboratories performing HER2 testing.
对于所有新确诊的浸润性乳腺癌以及首次复发的乳腺癌只要有可能建议测定肿瘤ER和PR以及HER2状态。NCCN乳腺癌小组支持CAP关于解剖病理学实验室完成HER2检测的认证。

HER2 status can be assessed by measuring the number of HER2 gene copies using in situ hybridization (ISH) techniques, or by a complementary method in which the quantity of HER2 cell surface receptors is assessed by IHC. Assignment of HER2 status based on mRNA assays or multigene arrays is not recommended. The accuracy of HER2 assays used in clinical practice is a major concern, and results from several studies have shown that false-positive as well as false-negative HER2 test results are common. A joint panel from ASCO and CAP has issued updated HER2 testing guidelines to avoid such false-positive or false-negative results. These updated guidelines have been published in the Archives of Pathology & Laboratory Medicine and ASCO's Journal of Clinical Oncology. The NCCN Panel endorses these updated ASCO/CAP recommendations for quality HER2 testing and has outlined these recommendations in Principles of HER2 Testing.
HER2状态可以通过使用原位杂交(ISH)技术检测HER2基因拷贝数评估,或通过IHC评估其细胞表面HER2受体的数量作为补充手段。不推荐根据mRNA分析或多基因阵列指定HER2状态。临床实践使用的HER2分析的准确性是一个主要的担心,若干研究结果已证明HER2检测假阳性以及假阴性结果常见。为了避免这种假阳性或假阴性结果ASCO与CAP联合小组已发布了更新的HER2检测指南。这些更新的指南已刊登在病理学&实验室医学文献和ASCO的《临床肿瘤学杂志》。NCCN小组支持这些更新的关于HER2检测质量的ASCO/CAP推荐并且已概述在HER2检测原则方面的这些推荐。

HER2 testing should be performed in laboratories accredited by CAP or another equivalent authority to carry out such testing. Further, these laboratories should have standardized HER2 testing procedures in place, as well as programs to periodically evaluate the proficiency of personnel performing HER2 testing. HER2 test reports should also include information on site of tumor, specimen type, histologic type, fixation method and time, block examined, and details on the HER2 testing method(s) used. Clinicians should be familiar with the significance of these criteria when making clinical recommendations for an individual patient.
HER2检测应该在CAP认可的实验室完成或另外的具有同等效力的部门开展这种检测。此外,这些实验室应该具有标准化的HER2检测程序以及定期评估HER2检测人员熟练程度的计划。HER2检验报告也应该包括肿瘤部位、标本类型、组织学类型、固定方法与时间、配伍检测以及使用的HER2检测方法细节方面的信息。当对一例具体患者做出临床推荐时临床医生应该熟悉这些标准的重要性。

HER2-Positive Result
HER2阳性结果

Consistent with the ASCO/CAP guidelines, the NCCN Panel considers either IHC or ISH with either a single or dual probe as an acceptable method for making an initial determination of HER2 tumor status. Breast cancer tumors are classified as HER2-positive if they are scored as 3+ by an IHC method defined as uniform membrane staining for HER2 in 10% or more of tumor cells or demonstrate HER2 gene amplification by an ISH method (single probe, average HER2 copy number 6.0 signals/cell; dual probe HER2/CEP17 ratio 2.0 with an average HER2 copy number 4.0 signals/cell; dual probe HER2/ chromosome enumeration probe (CEP)17 ratio 2.0 with an average HER2 copy number<4.0 signals/cell; HER2/CEP17 ratio <2.0 with an average HER2 copy number 6.0 signals/cell).
ASCO/CAP指南一致,NCCN小组认为或者IHC或者ISH加上单或双探针为初步测定肿瘤HER2状态的一种可接受的方法。乳腺癌肿瘤可分为HER2阳性:免疫组化评分3+定义为≥10%的肿瘤细胞HER2均匀膜染色或原位杂交法显示HER2基因扩增(单探针,平均每个细胞HER2拷贝数≥6.0;双探针HER2/CEP17比值≥2.0加上平均每个细胞HER2拷贝数≥4.0;双探针HER2/染色体计数探针(CEP)17比值≥2.0加上平均每个细胞HER2拷贝数<4.0;HER2/CEP17比值<2.0加上平均每个细胞HER2拷贝数≥6.0)。

High average copy number of HER2 (6.0 signals/cell) is considered positive regardless of the HER2/CEP17 ratio. The rationale cited by the joint committee for including rare scenarios such as HER2 positivity when dual probe HER2/CEP17 ratio is greater than or equal to 2.0 and average HER2 copy number is less than 4.0 signals/cell is that the first- generation trials of adjuvant trastuzumab included a small number of patients with a HER2/CEP17 ratio greater than or equal to 2.0 and an average HER2 copy number less than 4.0 signals/cell. There is no trend in these data, suggesting that these patients were not responsive to trastuzumab and the trastuzumab has a favorable safety profile.
HER2平均拷贝数高(≥6.0/细胞)认为是阳性而不考虑HER2/CEP17比值。联合委员会包括了罕见情况如双探针HER2/CEP17比值≥2.0而平均每个细胞HER2拷贝数<4.0时HER2阳性引用的理论基础是第一代辅助性曲妥珠单抗试验收入了少量HER2/CEP17比值≥2.0而每个细胞HER2拷贝数<4.0的患者。这些数据没有倾向,提示这些患者对曲妥珠单抗无应答而曲妥珠单抗具有良好的安全性。

Equivocal Result
可疑结果

The NCCN Panel agrees with the ASCO/CAP HER2 committee that results of IHC are equivocal if scored as IHC 2+ “based on circumferential membrane staining that is incomplete and/or weak/moderate and within greater than 10% of the invasive tumor cells or complete and circumferential membrane staining that is intense and within less than or equal to 10% of the invasive tumor cells.” In such cases, the panel recommends reflex testing using the ISH method on the same specimen or repeating tests if a new specimen is available.
NCCN小组和ASCO/CAP HER2委员会的意见一致:如果“>10%的浸润性肿瘤细胞膜周围染色不完整和/或弱/中等或≤10%的浸润性肿瘤细胞强而完整的膜周围染色”免疫组化评分为2+则认为是免疫组化结果可疑。在这种病例中,专家组推荐使用原位杂交法对同一个标本重检或者如果可获得新的标本重复检测。

Similarly, samples with equivocal results by an ISH assay (for example, single probe ISH average HER2 copy number 4.0 and<6.0 signals/cell; and dual probe HER/CEP17 ratio <2.0 with an average HER2 copy number 4.0 signals/cell) must be confirmed by reflex testing using the IHC method on the same specimen or repeating tests if a new specimen is available.
同样,原位杂交分析可疑的标本(例如,单探针原位杂交平均HER2拷贝数每个细胞≥4.0且<6.0;以及双探针HER/CEP17率<2.0且平均HER2基因拷贝数每个细胞≥4.0)必须使用免疫组化法对同一个标本重检确认或者如果可获得新的标本重复检测。

本文为转载文章,如有侵权请联系作者删除。

有帮助
期待更新

张品良 副主任医师

山东省肿瘤医院 呼吸肿瘤内科

问医生 去挂号

更多文章

乳腺癌病理学评估 ... 的相关咨询
乳腺癌病理学评估 ... 的相关疾病
由于相关规范,IOS用户暂不可在小程序订阅