乳腺癌前哨淋巴结微小转移的检测

Objective： To study the best examination method of micrometastases in sentinel lymph node （SLN） of breast cancer and study the related factors with micrometastases. Methods： By step serial sectioning technique and immunohistochemistry, 121 SLNs and 44 tumors of 59 cases were examined. Results： Micrometastases was found in 17 SLNs （14%） of 14 （24%） cases. The more sections or examination methods, the more micrometastases were found. Micrometastases was related with the tumor size and the expression of c-erbB2, MMP-2 and VEGF. Conclusion： The best examination method is making sections at two levels with 100 pm interval and combination of HE staining and mucl immunohistochemistry. We can get the excellent detection/cost by this method. Micrometastases is a bad prognostic factor.     

Significance and management of micrometastases in patients with breast cancer

The routine use of sentinel lymph node biopsy in the care of patients with invasive breast cancer has led to an increase in the identification of micrometastases in the axillary lymph nodes. Currently, the clinical relevance of this small-volume disease is debated. This article reviews the most current literature with respect to detection of micrometastases and isolated tumor cells in sentinel lymph nodes, the prognostic significance of these findings, and recommendations for locoregional and systemic treatment.     

乳腺癌前哨淋巴结微转移的非前哨淋巴结转移率探讨

目的：探讨乳腺导管内癌（DCIS）和浸润性导管癌前哨淋巴结（SN）微转移对非SN转移率的影响。方法：采用常规HE染色和CK19免疫组化法回顾性研究24例DCIS和41例浸润性导管癌患者的SN微转移和非SN转移情况。结果：对65例早期乳腺癌患者的103枚SN进行了研究。24例DCIS患者中，1例SN转移其非SN也有转移（4．2％），23例SN阴性的DCIS中未发现SN微转移；41例浸润性导管癌患者中，10例SN转移中6例有非SN转移；其余31例SN阴性患者中，CK19免疫组化法染色发现SN微转移4例（12．9％），其中1例患者有非SN转移；SN微转移患者中非SN转移率25．0％（1／4），SN转移患者中非SN转移率63．6％（7／11），多枚SN仅1枚微转移患者中的非SN转移率50．0％（1／2）。结论：初步研究提示，CK19免疫组化法检测SN微转移有助提高SN转移的发现，SN微转移患者若放弃腋淋巴结清除可能造成转移灶的残留。SN微转移的研究可作为腋淋巴结清除或放疗的一个参考指标。     

Distinction between isolated tumor cells and micrometastases in breast cancer

BACKGROUND: In routine practice, the distinction between isolated tumor cells (ITC) and micrometastases (MIC) in patients with breast cancer is sometimes difficult to discern. The authors assessed differences in classifying patients according to the American Joint Commission on Cancer (AJCC) and the International Union Against Cancer (UICC) definitions and method of sizing. METHODS: We assessed the characteristics of metastatic deposits in only 1 involved lymph node in 337 patients with operable breast cancer (median follow-up, 15.3 years). When sizing multiple clusters, either the diameter of the area with close clusters (Method 1) or the size of the largest cluster (Method 2) was taken into account. Patients were classified and their survival was assessed according to the 2 sizing methods and the criteria used for definitions (size in AJCC; size and topography in UICC). RESULTS: With the AJCC definitions, 32 patients would be differently classified according to the method of sizing. With the UICC definitions, some patients with parenchymal ITC would be classified as pN1mi, 38 by Method 1 and 53 by Method 2. Some pathologists would classify the 66 patients who had isolated capsular vascular invasion as pN0. Classification was uncertain in 136 (40%) to 151 (45 %) patients. Survival was not significantly different between pN0(i+) and pN1(mi) patients. CONCLUSIONS: The distinction between ITC and MIC was often difficult and without any prognostic significance. Precise guidelines are more useful for staging than for therapy. Thus, complete axillary dissection is usually performed in pN0(i+) and pN1(mi) patients, whereas chemotherapy is not indicated or debatable when MIC is the only 1 pejorative criterion.     

乳腺癌前哨淋巴结微转移的非前哨淋巴结转移率探讨

目的:探讨乳腺导管内癌(DCIS)和浸润性导管癌前哨淋巴结(SN)微转移对非SN转移率的影响。方法:采用常规HE染色和CK19免疫组化法回顾性研究24例DCIS和41例浸润性导管癌患者的SN微转移和非SN转移情况。结果:对65例早期乳腺癌患者的103枚SN进行了研究。24例DCIS患者中,1例SN转移其非SN也有转移(4·2%),23例SN阴性的DCIS中未发现SN微转移;41例浸润性导管癌患者中,10例SN转移中6例有非SN转移;其余31例SN阴性患者中,CK19免疫组化法染色发现SN微转移4例(12·9%),其中1例患者有非SN转移;SN微转移患者中非SN转移率25·0%(1/4),SN转移患者中非SN转移率63·6%(7/11),多枚SN仅1枚微转移患者中的非SN转移率50·0%(1/2)。结论:初步研究提示,CK19免疫组化法检测SN微转移有助提高SN转移的发现,SN微转移患者若放弃腋淋巴结清除可能造成转移灶的残留。SN微转移的研究可作为腋淋巴结清除或放疗的一个参考指标。     

免疫组织化学和RT-PCR法检测乳腺癌骨髓和前哨淋巴结微小转移的临床研究

目的探讨免疫组织化学(IHC)和RT-PCR法检测乳腺癌骨髓和前哨淋巴结(SLN)微小转移的灵敏度及临床意义。方法留取乳腺癌改良根治术腋窝淋巴结HE染色证实阴性的病人的胸骨骨髓血和SLN,分别采用IHC和RT-PCR方法检测其微小转移情况。结果62例中,骨髓样本RT-PCR检测15例阳性表达,其中9例IHC检测也为阳性,二者结果有较好一致性(kappa=0.6945),检出率有统计学差异(P=0.0412);SLN样本RT-PCR法有13例KT19mRNA表达,其中7例IHC检出KT19阳性细胞,二者结果一致性较好(kappa=0.6483),检出率有统计学差异(P=0.0412);骨髓和SLN同时表达KT19mRNA仅3例,无显著相关(P=0.796);原发肿瘤大小和骨髓KT19mRNA表达率有关联(P=0.003)。结论常规检查未发现远处和腋窝淋巴结转移,骨髓和SLN可检出微小转移,RT-PCR较IHC更灵敏,肿瘤大小与骨髓微小转移有关联。由于骨髓和腋窝淋巴结微小转移不一定同步出现,选用灵敏方法对不同组织同时进行检测可能更具临床价值。     

Cross-validation of three predictive tools for non-sentinel node metastases in breast cancer patients with micrometastases or isolated tumor cells in the sentinel node

Background

We cross-validated three existing models for the prediction of non-sentinel node metastases in patients with micrometastases or isolated tumor cells (ITC) in the sentinel node, developed in Danish and Finnish cohorts of breast cancer patients, to find the best model to identify patients who might benefit from further axillary treatment.

Material and method

Based on 484 Finnish breast cancer patients with micrometastases or ITC in sentinel node a model has been developed for the prediction of non-sentinel node metastases. Likewise, two separate models have been developed in 1577 Danish patients with micrometastases and 304 Danish patients with ITC, respectively. The models were cross-validated in the opposite cohort.

Results

The Danish model for micrometatases was accurate when tested in the Finnish cohort, with a slight change in AUC from 0.64 to 0.63. The AUC of the Finnish model decreased from 0.68 to 0.58 when tested in the Danish cohort, and the AUC of the Danish model for ITC decreased from 0.73 to 0.52, when tested in the Finnish cohort. The Danish micrometastatic model identified 14–22% of the patients as high-risk patients with over 30% risk of non-sentinel node metastases while less than 1% was identified by the Finish model. In contrast, the Finish model predicted a much larger proportion of patients being in the low-risk group with less than 10% risk of non-sentinel node metastases.

Conclusion

The Danish model for micrometastases worked well in predicting high risk of non-sentinel node metastases and was accurate under external validation.     

Tumour-positive sentinel node findings in patients with ductal carcinoma in situ

BACKGROUND: Our aim was to evaluate the prevalence of and risk factors for tumour-positive sentinel node (SN) findings in patients with ductal carcinoma in situ (DCIS). METHODS: Altogether 1,470 patients underwent sentinel node biopsy (SNB) between April 2001 and March 2005 in our unit. According to a histopathological review, 11 of them had microinvasive and 74 pure DCIS and were included in the study. RESULTS: Five patients (7%) with pure DCIS had SN metastases. Three of them had isolated tumour cells (ITC) only. Axillary clearance without further metastatic findings was performed in three patients. The median histological size of DCIS was larger, 50 (45-60) mm in patients with metastatic SN findings than the median of 18 (2-110) mm in those with tumour-negative SN, P=0.0103. All five patients with metastatic SN findings underwent mastectomy. Metastatic SN findings were detected in one (9%) patient with microinvasive DCIS. CONCLUSIONS: Metastatic SN findings in patients with pure DCIS may be a sign of missed invasion.     

Prognosis of breast cancer patients treated with sentinel node biopsy in Japan

BACKGROUND: Sentinel node biopsy predicts accurate pathological nodal staging. The survival of node-negative breast cancer patients should be evaluated between the patients treated with sentinel node biopsy alone and those treated with axillary lymph node dissection. METHODS: Ninety-seven patients with negative axillary nodes underwent sentinel node biopsy immediately followed by axillary lymph node dissection between January 1998 and June 1999 (the ALND group). Since then, if sentinel lymph nodes were negative on the frozen-section diagnosis, 112 patients underwent sentinel node biopsy alone without axillary lymph node dissection between July 1999 and December 2000 (the SNB group). We retrospectively observed the outcome of the two study groups. RESULTS: Median follow-up was 52 months in all patients. Relapse-free survival rates at 3 years in the ALND and SNB groups were 94% and 93%, respectively. Five of the 112 patients in the SNB group had overt axillary metastases. Three of them with axillary metastases alone were treated with delayed axillary lymph node dissection. These three patients have been free of other events for 3 years after local salvage treatment. CONCLUSIONS: Sentinel node biopsy will emerge as a standard method to diagnose axillary nodal staging for clinically node-negative breast cancer patients.     

乳腺癌前哨淋巴结活检研究进展

近年来,乳腺癌的发病率越来越高,乳腺癌治疗方式也在不断改进,但手术仍然是早期乳腺癌治疗的主要手段。对于早期乳腺癌,前哨淋巴结活检术（sentinel lymph node biopsy,SLNB）是一种安全、精确的手术方式,已逐渐替代腋窝淋巴结清扫术（axillary lymph node dissection,ALND）成为早期乳腺癌治疗的标准术式。随着研究的深入,SLNB的应用范围更广,术后生活质量显著改善,但其操作尚需要进一步统一规范。在前哨淋巴结微转移、宏转移、前哨淋巴结活检阳性的老年患者以及新辅助化疗的前哨淋巴结活检等方面尚未达成共识,还需要更多大型多中心前瞻性的随机试验来进一步论证。     

前哨淋巴结活检在早期乳腺癌患者腋窝管理中的研究进展

传统的观点认为腋窝淋巴结清扫(axillary lymph node dissection,ALND)是前哨淋巴结(sentinellymph node,SLN)阳性乳腺癌患者的标准治疗方法,而ALND容易引起上肢水肿、功能障碍等术后并发症,影响患者生活质量.近几年研究显示,对于SLN阳性的早期乳腺癌,并非所有患者都需...     

术中冰冻切片联合快速免疫组织化学染色检测乳腺癌前哨淋巴结微转移的临床研究

目的探讨术中冰冻切片联合快速免疫组织化学检测对乳腺癌前哨淋巴结（SLN）微转移的诊断价值,分析SLN微转移与临床各因素的关系。方法对43例乳腺癌患者行前哨淋巴结活检（SLNB）,切除SLN送快速病理学检查。以100μm为间隔,进行连续切片（SS）,并做冰冻切片HE染色及快速免疫组织化学染色检测SLN微转移[检测广谱细胞角蛋白（pan—CK）及上皮膜抗原（EMA）的表达];采用）（2检验或连续性校正x。检验对定性资料进行统计学分析。结果43例乳腺癌患者成功行SLNB,共检出SLN100枚。4例冰冻切片HE染色查见癌转移,39例HE染色阴性者继续行快速免疫组织化学染色检出微转移者6例。冰冻切片检测SLN癌转移率为9．3％（4／43）,冰冻切片联合术中快速免疫组织化学染色检测SLN癌转移率为23．3％（10／43）。两者的灵敏度、特异度、总符合率和假阴性率分别为36．4％／90．9％、100％／100％、83．7％／97．7％、63．6％／9．1％。SLN微转移与月经状态、肿瘤分期、组织学类型、肿瘤位置、激素受体状态及人表皮生长因子受体2（HER-2）状态无明显关系（P〉0．05）。结论术中冰冻切片联合快速免疫组织化学染色法提高了SLN微转移的检出率,减少了假阴性率,且安全、快速、花费少,值得在临床推广使用。     

临床腋窝淋巴结阳性乳腺癌患者内乳区前哨淋巴结活检术研究*

目的：评估临床腋窝淋巴结阳性乳腺癌患者行内乳区前哨淋巴结活检术（IM-SLNB）的临床意义。方法：2013年6 月至2014年10月对山东省肿瘤医院乳腺病中心就诊的64例临床腋窝淋巴结阳性的原发性乳腺癌患者行前瞻性单臂入组研究,采取腋窝淋巴结清扫术,同时均应用新的核素注射技术进行IM-SLNB。结果：64例患者中内乳区前哨淋巴结（IM-SLN）显像为38例,显像率为59.4%（38/ 64）。 38例IM-SLN 显像患者中IM-SLNB 成功率为100%（38/ 38）,并发症发生率为7.9%（3/ 38）,IM-SLN 转移率为21.1%（8/ 38）。 肿瘤位于内上象限和腋窝淋巴结转移数目较多的患者,其IM-SLN 转移率较高（P < 0.001 和P = 0.017）。 患者临床获益率为59.4%（38/ 64）,其中12.5%（8/ 64）另接受了内乳区放疗、46.9%（30/ 64）避免了不必要的内乳区放疗。结论：临床腋窝淋巴结阳性的乳腺癌应进行IM-SLNB,尤其对于肿瘤位于内上象限及怀疑存在较多腋窝淋巴结转移数目的患者,以获得内乳区淋巴结的转移状态,指导乳腺癌患者内乳区放疗。     

乳腺癌前哨淋巴结活检的安全性

循证医学Ⅰ、Ⅱ级证据支持乳腺癌前哨淋巴结活检（SLNB）的安全性。本文就SLNB对腋窝淋巴结的准确分期、前哨淋巴结阴性患者SLNB替代腋清扫术后腋窝复发率和并发症、SLNB的放射安全性、SLNB新的适应症进行讨论。     

An axilla scoring system to predict non-sentinel lymph node status in breast cancer patients with sentinel lymph node involvement

Background. Axillary lymph node dissection (ALND) is the current standard of care for breast cancer patients with sentinel lymph node (SN) involvement. However, the SN is the only involved axillary node in a significant proportion of these patients. Here we examined factors predictive of non-SN involvement in patients with a metastatic SN, in order to develop a scoring system for predicting non-SN involvement.Materials and Methods. This study was based on a prospective database of 337 patients who underwent SN biopsy for breast cancer, of whom 81 (24) were SN-positive; we examined factors predictive of non SN involvement in the 71 of these 81 women who underwent complementary ALND. All clinical and histological criteria were recorded and analysed according to non-SN status, by using Chi-2 analysis, Students t-test, and multivariate logistic regression.Results. Univariate analysis showed a significant association between non-SN involvement and histological primary tumor size (p=0.0001), SN macrometastasis (p=0.01), the method used to detect SN metastasis (H&E versus immunohistochemistry) (p=0.03), the number of positive SNs (p=0.049), the proportion of involved SNs among all identified SNs (p=0.0001) and lymphovascular invasion (p=0.006). Histological primary tumor size (p=0.006), SN macrometastasis (p=0.02) and the proportion of involved SNs among all identified SNs (p=0.03) remained significantly associated with non-SN status in multivariate analysis. Based on the multivariate analysis, we developed an axilla scoring system (range 0–7) to predict the likelihood of non-SN metastasis in breast cancer patients with SN involvement.Conclusion. In patients with invasive breast cancer and a positive SN, histological primary tumor size, the size of SN metastases, and the proportion of involved SNs among all identified SNs were independently predictive of non-SN involvement.     

Intradermal radioisotope injection optimises sentinel lymph node identification in breast cancer

AIM: Currently there is no consensus on the optimal technique for sentinel lymph node (SLN) identification in patients with breast cancer. The aim was to compare the efficacy of intraparenchymal and intradermal isotope injection in sentinel lymph node mapping for breast cancer. METHODS: One hundred and twenty-five patients with histologically confirmed invasive breast cancer underwent SLN mapping using radioisotope and isosulphan blue dye followed by a back-up axillary dissection. The first 80 patients had intraparenchymal (IP) injection of radioisotope given in four portions around the tumor. The remaining 45 patients had an intradermal (ID) injection given at a single site over the tumour. Both groups had isosulphan blue dye injected around the tumour. Sentinel node(s) were identified using a combination of lymphoscintigraphy, blue dye and an intra-operative hand held gamma probe. RESULTS: The preoperative lymphoscintigram (LSG) demonstrated a SLN significantly more often in the ID isotope group compared to the IP isotope group (P=0.002). A combination of blue dye and isotope successfully located the SLN in 96% of the intraparenchymal group and 100% of the intradermal group. CONCLUSION: Our results suggest that intradermal isotope injection in combination with intraparenchymal blue dye optimises the localization of the sentinel lymph node in breast cancer.