Detection of lymph nodes micrometastases in breast carcinoma using immunohistochemistry for cytokeratin 8

The lymph nodes status is one of the most important prognostic factors in breast cancer. The routine hematoxilin-eosin staining is efficient for the metastases detection only when there is a large number of tumor cells, while a small number of metastatic cells can easily remain undetectable. For those situations, the immunohistochemistry for cytokeratins, markers of the epithelial cells, is a very sensitive method. We have investigated the cytokeratin 8 expression in 10 primary breast carcinomas and in the corresponding axillary lymph nodes, comparing with hematoxilin-eosin. The routine examination has detected axillary lymph nodes metastases in six cases, confirmed by the immunohistochemistry for cytokeratin 8. Four cases were diagnosed as negative for the axillary lymph nodes metastases by the hematoxilin-eosin staining. In all those four cases, immunohistochemistry for cytokeratin 8 has detected a small number of tumor cells, either spread in the lymph nodes tissues, either confluent as small islets.     

结直肠癌淋巴结微转移病灶中CK20检测方法的比较

目的 比较免疫组织化学和逆转录-聚合酶链反应(RT-PCR)方法对结直肠癌淋巴结微转移病灶中CK20的检测价值.方法 对40例结直肠癌患者共326例经HE染色证实无转移的淋巴结,使用RT-PCR技术检测CK20 mRNA,并与免疫组织化学染色检测方法进行比较,以寻找更为敏感的淋巴结微转移检测方法.结果 免疫组织化学法和RT-PCR分别发现41枚和105枚微转移淋巴结,两种方法发现的微转移阳性率分别为12.8%和32.2%,两者差异有统计学意义(P<0.05).结论 RT-PCR法是比免疫组织化学染色法更为敏感的检测结直肠癌淋巴结微转移的方法.     

High incidence of micrometastases in breast cancer sentinel nodes

BACKGROUND: Sentinel lymph node biopsy (SLNB) is being investigated as an alternative to formal axillary dissection in early breast cancer. Avoiding the morbidity of unnecessary axillary dissection is seen as the main potential benefit of SLNB. Sentinel lymph node biopsy also allows enhanced pathological analysis. A series of 62 sentinel node (SN) biopsies demonstrating a high incidence of micrometastases is presented here. METHODS: All SN were initially examined and reported by H&E staining. All negative SN were analysed after staining with polyclonal anticytokeratin antibody. RESULTS: Sixty-two patients underwent SLNB at Royal Melbourne Hospital between May 1998 and February 2000. One or more SN was identified in 51/62 patients. A total of 10/51 contained metastases identified after H&E staining. There was one false negative. A total of 10/41 patients with H&E-negative SN had micrometastases identified on immunohistochemistry (IHC). Micrometastases were more common in patients with larger tumours, with disease found in the H&E-negative SN of 1/17 T1a and T1b (1-10 mm), 4/15 T1c (11-20 mm), and 5/9 T2 (20-50 mm) tumours. CONCLUSION: Sentinel lymph node biopsy can accurately assess the axilla in most patients with early breast cancer. A significant proportion of histologically negative SN will have micrometastases identifiable with IHC. Although the clinical significance of such metastases is uncertain, the available evidence suggests that these patients have a poorer prognosis than other patients with negative lymph nodes.     

胃癌前哨淋巴结的检测及意义

胃癌是消化系统最常见的恶性肿瘤.随着内镜检查技术的广泛应用,早期胃癌在胃癌诊断中所占的比例明显提高,这也促使以微创手术治疗胃癌成为近年来讨论的热点.其中,前哨淋巴结导航手术(sentinel node navigation surgery,SNNS)越来越引起外科医生的重视.前哨淋巴结(sentinel lymph node,SLN)的概念最早由Cabanas[1]于1977年提出,是指首先引流肿瘤淋巴液并最先发生转移的淋巴结.     

Therapeutic relevance of breast cancer micrometastases in sentinel lymph nodes

BACKGROUND AND METHODS: This review examines the various methods of detecting occult breast cancer metastasis in the sentinel lymph node (SLN). The prognostic relevance of such micrometastases and isolated tumour cells, and their impact on stage migration and decision making with respect to axillary dissection and adjuvant systemic therapy, are discussed. RESULTS: Examination of SLNs by serial section with haematoxylin and eosin and/or immuno histochemical staining significantly increases the detection rate of micrometastases, even in patients with very small (T1) tumours. However, the prognostic relevance of isolated tumour cells and small micrometastases is uncertain. Moreover, deciding which patients might benefit from axillary dissection is complicated by the fact that adjuvant radiotherapy and systemic chemotherapy alone may eradicate most micrometastases. CONCLUSION: Ongoing randomized trials comparing the results of SLN biopsy alone with those of axillary dissection should answer the question of whether isolated tumour cells and small micrometastases are clinically relevant. This should also indicate which patients with SLN micrometastasis are likely to benefit from axillary dissection. In this sense, SLN biopsy must be considered still to be at an investigative stage; outwith clinical trials complete axillary dissection should be performed on all patients with SLN micrometastasis.     

Proliferative activity of micrometastases in the lymph nodes of patients with gastric cancer

BACKGROUND: Immunohistochemically detectable isolated tumour clusters (ITCs) with a diameter of less than 0.2 mm have been regarded as non-metastatic lesions, because of a lack of proliferative activity. This study investigated the proliferative activities of ITCs. METHODS: Three hundred and eight patients with primary gastric cancer diagnosed as pN0 by routine histological examination were studied. All patients underwent curative resection. Sections of lymph nodes were stained by double-immunostaining methods using anti-cytokeratin and anti-Ki-67 antibody (MIB-1). RESULTS: ITCs were detected in 77 nodes from 37 patients, designated as having pN0(i+) lesions. Seventy of 77 lymph nodes with ITCs were detected in the N1 station, and seven were found in the N2 station. Of 25 single isolated cancer cells, 12 showed positive labelling with MIB-1, and 49 of 52 ITCs with clusters of cancer cells had positive MIB-1 labelling (mean(s.d.) 46.6(30.1) per cent). Five of the 37 patients with ITCs (pN0(i+)) versus one of the 271 patients with no evidence of ITCs (pN0(i-)) died from recurrence. Patients with ITCs had a significantly worse prognosis than those without (P = 0.014). CONCLUSION: ITCs have a high proliferative activity and may have the potential to evolve into established lymph node metastasis.     

Detection of sentinel lymph nodes in patients with papillary thyroid cancer

OBJECTIVES: To determine the feasibility of sentinel lymph node biopsy as a means of evaluating the cervical lymph nodes of patients with papillary thyroid cancer. METHODS: Isosulfan blue dye was injected around the tumour of 68 patients with papillary thyroid cancer; sentinel lymph node biopsy was performed in addition to subtotal thyroidectomy and central and modified lateral neck lymph node dissections. Surgical specimens were examined by routine processing to determine whether metastasis was present. RESULTS: Sentinel lymph nodes were identified in 63 (92.6%) of the 68 patients. There was concordance between the sentinel lymph node status and the final regional lymph node status in 58 (92.1%) of the 63 patients. There were five false-negative cases. Sentinel lymph node biopsy had a sensitivity of 87.5% (35/40), specificity of 100% (23/23), positive predictive value of 100% (35/35), negative predictive value of 82.1% (23/28), and accuracy of 92.1% (58/63). CONCLUSIONS: Sentinel lymph node biopsy may allow discrimination between patients with true lymph-node-negative papillary thyroid carcinoma and those with non-palpable metastatic lymph nodes. It may also be helpful in diagnosing metastases and avoiding unnecessary lymph node dissection in thyroid cancer.     

乳腺癌前哨淋巴结微转移的研究

目的：提高乳腺癌前哨淋巴结（SLN）病理诊断的准确性，为手术彻底切除肿瘤提供依据。方法：应用亚甲蓝生物染色的方法确定60例Ⅰ、Ⅱ期乳腺癌SLN并活检，44（73．3％）例SLN取材成功。每一枚SLN均进行冰冻病理切片、石蜡病理和角蛋白Keratinl9（CK-19）逆转录聚合酶链反应（RT—PCR）检测。结果：44例SLN冰冻病理切片、石蜡病理切片和CK-19诊断的灵敏度和特异度分别是77．8％和100．0％、88．9％和100．0％、100．0％和82．9％，诊断符合率分别为95．5％、97．7％和86．4％，诊断指数分别为0．778、0．889和0．829。结论：CK-19检测可进一步提高乳腺癌SLN微转移的检出率，提高SLN活检的准确性。但CK-19检测与冰冻病理病理检查联合应用可提高诊断的准确率和临床的可操作性。     

Mapping sentinel nodes in patients with early-stage gastric carcinoma

BACKGROUND: Nodal status in gastric carcinoma is related not only to prognosis but also to the extent of nodal dissection. However, a method for accurate assessment of nodal status during operation has not been established. This study aimed to map the sentinel nodes of gastric carcinoma and to estimate the clinical usefulness of sentinel node biopsy. METHODS: Following laparotomy, a vital dye (0.2 ml 2 per cent patent blue) was injected through a gastroscope into the submucosal layer at four sites around a clinical T1 gastric carcinoma. The dye immediately appeared at the serosal surface and stained lymphatic vessels and nodes. The stained nodes were removed and examined by frozen sectioning. RESULTS: The assay was successful in mapping the lymphatic basins in 203 (96.2 per cent) of 211 patients. The dye stained one or more metastatic nodes in 31 patients, but failed to indicate a metastatic node in four patients with a large involved node. Meticulous postoperative examination of all resected nodes in the standard paraffin slices revealed no new metastases. The accuracy of the assay was 98.0 per cent. CONCLUSION: The method was accurate in predicting nodal status in patients with early-stage gastric carcinoma.     

Detection of sentinel node micrometastasis by step section and immunohistochemistry in patients with prostate cancer

PURPOSE: The role of step section and immunohistochemistry for diagnosing sentinel node micrometastases and the sentinel node concept in patients with prostate cancer was investigated. In patients administered neoadjuvant hormone therapy its influence on the sentinel node concept and metastasis diagnosis was also investigated. MATERIALS AND METHODS: Of 62 patients without metastasis enrolled in our study 42 were eligible for analysis. The prostate was injected with the radioactive tracer (99m)technetium phytate 5 to 6 hours before surgery. A planar image and a fusion image with x-ray computerized tomography and single photon emission computerized tomography were obtained 3 hours after tracer injection. Extended lymph node dissection and lymphatic mapping were performed to verify the sentinel node concept. Lymph node metastasis was histologically confirmed by routine hematoxylin and eosin, and thereafter by immunohistochemistry using 250 mum step-sectioned slides. RESULTS: The mean number of dissected lymph nodes was 26.3 per patient. Hot nodes were noted in 41 of 42 patients. The sensitivity and specificity of hot node prediction of lymph node metastasis were 92.3% and 100%, respectively. On routine hematoxylin and eosin examination lymph node metastases were found in 4 of 27 patients with and in 4 of 15 without neoadjuvant hormone therapy. Step section and immunohistochemistry identified micrometastasis in 5 more patients with neoadjuvant hormone therapy. CONCLUSIONS: The validity of the sentinel node concept in conjunction with the detection of micrometastases was considered to be high. Furthermore, it was suggested that the efficacy of metastasis diagnosis may also be enhanced, especially in patients receiving neoadjuvant hormone therapy.     

Intradermal radioisotope is superior to peritumoral blue dye or radioisotope in identifying breast cancer sentinel nodes

BACKGROUND: Sentinel lymph node (SLN) mapping and biopsy have emerged as the technique of choice for axillary staging of breast cancer. Several methods have been developed to identify SLNs, including peritumoral or intradermal injection of isosulfan blue dye or technetium sulfur colloid (TSC). We hypothesize that intradermal TSC is the optimal mapping technique and can be used alone to identify SLNs. STUDY DESIGN: From March 1997 through January 2001, 180 women with T1 and T2 invasive breast cancer and clinically negative axilla underwent SLN mapping and biopsy. Peritumoral TSC was injected in 74 patients, 62 of whom also received peritumoral blue dye. Intradermal TSC (above tumor) was performed in 94 patients, 76 of whom also received peritumoral blue dye. Technetium-rich nodes were identified intraoperatively using a hand-held gamma probe and blue nodes were identified visually. Hematoxylin- and eosin-stained SLN sections were examined by light microscopy for breast cancer metastases. RESULTS: Overall, the SLN mapping procedures were successful in 91% of patients. Peritumoral and intradermal TSC were successful in identifying SLNs in 78% and 97% of patients, respectively. Peritumorally injected isosulfan blue was successful in identifying 83% of SLNs. Intradermal TSC was found to be superior to peritumoral TSC and peritumoral blue dye in identifying SLNs (p = 0.00094, chi-squared, and p = 0.020, ANOVA). CONCLUSIONS: SLN mapping by intradermal TSC has a significantly higher success rate than peritumoral TSC or blue dye. There was minimal benefit in identifying additional SLNs with addition of peritumoral blue dye to intradermal TSC. So, SLN mapping and biopsy using intradermal-injected TSC can be used alone to effectively stage the axilla for breast cancer.     

腹腔镜下胃癌前哨淋巴结标示的临床应用及意义

目的：探讨腹腔镜下胃癌前哨淋巴结（SLN）检测的可行性及SLN活检预测胃周淋巴结转移状况的准确性,评价SLN活检在指导胃癌手术治疗中的应用价值。方法：2010年3—11月诊断明确的126例胃癌,在腹腔镜胃癌切除术中向肿瘤边缘正常胃壁浆膜下肌层、黏膜下层注射亚甲蓝标示SLN,腔镜下识别和切取蓝染淋巴结活检。以术后所有切除的胃周淋巴结常规病理检查结果为诊断金标准,观察SLN活检对预测胃周淋巴结有无肿瘤转移的准确性。结果：116例成功检测出SLN,检出率92．1％（116／126）。62例有淋巴结转移,其中前哨淋巴结与非前哨淋巴结（nSLN）均有转移47例,仅前哨淋巴结有转移10例,仅非前哨淋巴结有转移5例。前哨淋巴结预测胃周淋巴结转移的敏感性为91．9％（57／62）,准确率为94．0％（109／116）,假阴性率为8．1％（5／62）。结论：腹腔镜下胃癌SLN检测可行。通过SLN,术中能准确预测胃癌淋巴结转移状况,淋巴结转移阴性的胃癌患者,有望免除常规淋巴清扫。     

Area of nodal metastasis and radioisotope uptake in sentinel nodes of upper gastrointestinal cancer

BACKGROUND: Sentinel node navigation surgery has been introduced for the treatment of gastrointestinal tumor. As few studies have examined relationships between metastatic area and radioisotope uptake in sentinel nodes, the present study examined this relationship for gastric and esophageal cancers. METHODS: Subjects comprised 43 patients (esophageal cancer, n = 19; gastric cancer, n = 24) with < or =3 lymph node metastases in whom sentinel node mapping with radio-guided methods was performed. Radioisotope uptake was measured after surgery for all dissected lymph nodes. Metastatic area was calculated using the following formula: metastatic area (%) = (area of metastasis/total area of lymph node) x 100. Based on radioisotope uptake, lymph nodes were divided into RI(-) and RI(+) groups. RESULTS: In 35 patients, > or =1 metastatic node was present among the sentinel nodes. In 1 patient, no sentinel nodes were detected. No lymph node metastasis was found in sentinel nodes in the remaining seven patients. Lymph nodes were diagnosed as metastatic using preoperative imaging. Mean (+/-SD) metastatic area was significantly higher for RI(-) (68.3 +/- 20.5%) than for RI(+) (15.1 +/- 20.8%; P < 0.0001). Radioisotope uptake was decreased in lymph nodes with >60% metastatic area. CONCLUSIONS: The fact that radioisotope uptake is not detectable in some lymph nodes with >60% metastatic area must be considered when planning sentinel node navigation surgery.     

Intraoperative immunohistochemistry staining of sentinel nodes in breast cancer: clinical and economical implications

The study aimed to evaluate intraoperative immunohistochemistry (IHC) staining of sentinel nodes in primary breast cancer surgery. We analysed retrospectively 1209 consecutive sentinel node procedures and compared the rate of late positive metastases in sentinel node biopsy (SNB) and the duration of the surgical procedures before (n=706) and after (n=503) introducing intraoperative IHC on frozen section. We also did a cost analysis. Intraoperative IHC staining led to a lowering of the late positive SNB rate. Introducing IHC gave a decrease in the late positive rate from 93 to 52% (p<0.0001) for isolated tumour cell metastasis, from 56 to 36.4% (p<0.02) for micrometastasis, and from 16 to 5% (p<0.01) for macrometastasis. The surgical procedures were slightly prolonged for lumpectomies but not for mastectomies after introducing intraoperative IHC staining. The cost analysis showed an overall cost saving of approximately 40%. In conclusion, intraoperative IHC staining of the SNB lowered the late positive rate and gave an overall cost saving.     

Occurrence and prognostic implications of micrometastases in lymph nodes from patients with submucosal gastric carcinoma

BACKGROUND: The aims of this study were to assess the incidence of micrometastases of lymph nodes in patients with early gastric cancer invading the submucosal layer and to investigate the correlation between nodal micrometastases and malignancy potential to determine whether micrometastases of lymph nodes have prognostic significance, by use of an anticytokeratin immunohistochemical technique. METHODS: A total of 2272 lymph nodes taken from 88 patients (25.8 per case) were assessed by immunohistochemical technique by use of monoclonal anti-human cytokeratin 8 antibodies. Clinicopathologic parameters and prognosis were compared between patients with and without micrometastases. RESULTS: The incidence of nodal involvement by tumor cells in 88 patients with submucosal gastric cancer increased from 19.3% (17 patients) by hematoxylin-eosin (H&E) staining to 31.8% (28 patients) by cytokeratin immunostaining. The rate of positive node in this study increased from 1.0% (23 of 2272 nodes) by H&E staining to 2.5% (57 of 2272 nodes) by immunostaining (P = .0002). No correlation was observed between the incidence of lymph node micrometastases and various clinicopathologic parameters, including tumor site and size, histological differentiation, Lauren classification, gross tumor type, vascular and lymphatic invasion, and perineural invasion. There was no difference in disease-free survival, estimated by the Kaplan-Meier life-table method, between the micrometastasis-negative and -positive groups (95% and 92.9%, respectively). Multivariate analyses showed that tumor size and diffuse subtype by the Lauren classification were significant factors for survival time (P = .0042 and .014, respectively). CONCLUSIONS: Immunohistochemical staining with an anticytokeratin antibody seems to be of little prognostic value in patients with submucosal gastric carcinoma. Thus, this immunostaining technique does not offer a significant benefit of different strategies for additional therapy or follow-up over conventional pathologic staging with H&E staining.