Detection of occult lymph node tumor cells in node-negative gastric cancer patients / Identificação de células tumorais ocultas em linfonodos de pacientes com câncer gástrico classificados como pn0

ABSTRACT Background: The presence of lymph nodes metastasis is one of the most important prognostic indicators in gastric cancer. The micrometastases have been studied as prognostic factor in gastric cancer, which are related to decrease overall survival and increased risk of recurrence. However, their identification is limited by conventional methodology, since they can be overlooked after routine staining. Aim: To investigate the presence of occult tumor cells using cytokeratin (CK) AE1/AE3 immunostaining in gastric cancer patients histologically lymph node negative (pN0) by H&E. Methods: Forty patients (T1-T4N0) submitted to a potentially curative gastrectomy with D2 lymphadenectomy were evaluated. The results for metastases, micrometastases and isolated tumor cells were also associated to clinicopathological characteristics and their impact on stage grouping. Tumor deposits within lymph nodes were defined according to the tumor-node-metastases guidelines (7th TNM). Results: A total of 1439 lymph nodes were obtained (~36 per patient). Tumor cells were detected by immunohistochemistry in 24 lymph nodes from 12 patients (30%). Neoplasic cells were detected as a single or cluster tumor cells. Tumor (p=0.002), venous (p=0.016), lymphatic (p=0.006) and perineural invasions (p=0.04), as well as peritumoral lymphocytic response (p=0.012) were correlated to CK-positive immunostaining tumor cells in originally negative lymph nodes by H&E. The histologic stage of two patients was upstaged from stage IB to stage IIA. Four of the 28 CK-negative patients (14.3%) and three among 12 CK-positive patients (25%) had disease recurrence (p=0.65). Conclusion: The CK-immunostaining is an effective method for detecting occult tumor cells in lymph nodes and may be recommended to precisely determine tumor stage. It may be useful as supplement to H&E routine to provide better pathological staging.

RESUMO Racional: A presença de metástase em linfonodos é um dos indicadores prognósticos mais importantes no câncer gástrico. As micrometástases têm sido estudadas como fator prognóstico no câncer gástrico, sendo relacionadas à diminuição da sobrevida global e aumento do risco de recidiva da doença. Entretanto, sua identificação é limitada pela metodologia convencional, uma vez que podem não ser identificadas pela rotina histopatológica por meio da coloração de H&E. Objetivo: Investigar a presença de células tumorais ocultas através de imunoistoquimica utilizando as citoqueratinas (CK) AE1/AE3 em pacientes com câncer gástrico com linfonodos histologicamente classificados como negativos por H&E. Métodos: Quarenta pacientes (T1-T4N0) submetidos à gastrectomia potencialmente curativa com linfadenectomia D2 foram avaliados. A presença de metástases, micrometástases e células tumorais isoladas foram correlacionadas com características clínicopatológicas e impacto no estadiamento. Os depósitos tumorais nos linfonodos foram classificados de acordo com o sistema TNM (7º TNM). Resultados: Um total de 1439 linfonodos foi obtido (~36 por paciente). Células tumorais foram detectadas por imunoistoquimica em 24 linfonodos de 12 pacientes (30%). As células neoplásicas estavam presentes na forma isolada ou em cluster. Invasão tumoral (p=0,002), venosa (p=0,016), linfática (p=0,006) e perineural (p=0,04), assim como resposta linfocítica peritumoral (p=0,012) foram correlacionadas com linfonodos CK-positivos que originalmente eram negativos à H&E. Dois pacientes tiveram o estadiamento alterado, migrando do estádio IB para IIA. Quatro dos 28 CK-negativos (14,3%) e três dos 12 CK-positivos (25%) tiveram recorrência da doença (p=0,65). Conclusão: A imunoistoquimica é meio eficaz para a detecção de células tumorais ocultas em linfonodos, podendo ser recomendada para melhor determinar o estágio do tumor. Ela pode ser útil como técnica complementar à rotina de H&E, de modo a fornecer melhor estadiamento patológico.

Application of detection of expressions of hMAM combined with MMP-9 and C-erbB2 mRNA in peripheral blood in diagnosis of micrometastases of breast cancer / 吉林大学学报(医学版)

Objective:To explore the positive expressions of biological markers human mammaglobin (hMAM) combined with matrix metallopeptidase 9 (MMP-9) and human epidermal growth factor receptor 2 (C-erbB2) mRNA in peripheral blood of the breast cancer patients with micrometastases,and to clarify its clinical application value in diagnosis of the micrometastases in peripheral blood of the breast cancer patients.Methods:A total of 74 patients with breast cancer,21 patients with breast fibroadenoma and 10 healthy controls were selected as the subjects.All the patients received surgical treatment and the peripheral blood was collected.The mRNA expression levels of hMAM,MMP-9 and C-erbB2 in peripheral blood were measured by the real-time fluorescent quantitative PCR.The positive expression rates of detection of hMAM,MMP-9 and C-erbB2 were compared,and the differences in detection of hMAM combined with MMP-9 and C-erbB2 between the patients with different clinicopathologic features were analyzed.Results:In the breast cancer patients with lymph node metastasis,the differences of positive expression rates of MMP-9 and C-erbB2 mRNA were significant (x2=6.450,P＜0.05;x2=5.636,P＜0.05),and the difference of positive expression rate of hMAM mRNA was sigificant between HER-2 positive and negative patients (x2=5.804,P＜0.05).The positive expression rates of individual hMAM and combined with MMP-9 and C-erbB2 were 37.84％ (28/74),59.46％ (44/74) and 48.65％ (36/74) in the breast cancer patients,the combined postive expression rate of these three kinds of markers was 64.86 ％ (48/74),which were higher than those in healthy controls group (x2=5.676,P＜0.05;x2=3.102,P＞0.05;x2=5.339,P＜0.05;x2 =2.310,P＞0.05),fibroadenoma of breast group (x2 =8.438,P＜0.01;x2 =4.491,P＜ 0.05;x2 =7.982,P＜0.01;x2 =4.844,P＜0.05) and non-breast cancer group (healthy controls group+ breast fibroadenoma group) (x2 =13.093,P＜0.01;xx2 =6.471,P＜0.05;x2 =11.837,P＜0.01;x2 =6.103,P＜ 0.05).The positive expression rates of individual hMAM and the joint detection in the breast cancer patients at stage Ⅲ + Ⅳ were higher than those in the patients at stage Ⅰ + Ⅱ;the positive expression rates of individual hMAM and combined with C-erbB2 were statistically significant (x2 =5.157,P＜0.05;x2 =4.912,P＜0.05).Conclusion:hMAM has a low positive rate in the diagnosis of micrometastases in the breast cancer patients,while hMAM combined with MMP-9 and C-erbB2 detection could improve the positive rates.which presents some clinical application value for the early diagnosis of breast cancer micrometastases.

Application of detection of expressions of hMAM combined with MMP-9 and C-erbB2 mRNA in peripheral blood in diagnosis of micrometastases of breast cancer / 吉林大学学报(医学版)

Objective:To explore the positive expressions of biological markers human mammaglobin (hMAM) combined with matrix metallopeptidase 9 (MMP-9) and human epidermal growth factor receptor 2 (C-erbB2) mRNA in peripheral blood of the breast cancer patients with micrometastases,and to clarify its clinical application value in diagnosis of the micrometastases in peripheral blood of the breast cancer patients.Methods:A total of 74 patients with breast cancer,21 patients with breast fibroadenoma and 10 healthy controls were selected as the subjects.All the patients received surgical treatment and the peripheral blood was collected.The mRNA expression levels of hMAM,MMP-9 and C-erbB2 in peripheral blood were measured by the real-time fluorescent quantitative PCR.The positive expression rates of detection of hMAM,MMP-9 and C-erbB2 were compared,and the differences in detection of hMAM combined with MMP-9 and C-erbB2 between the patients with different clinicopathologic features were analyzed.Results:In the breast cancer patients with lymph node metastasis,the differences of positive expression rates of MMP-9 and C-erbB2 mRNA were significant (x2=6.450,P＜0.05;x2=5.636,P＜0.05),and the difference of positive expression rate of hMAM mRNA was sigificant between HER-2 positive and negative patients (x2=5.804,P＜0.05).The positive expression rates of individual hMAM and combined with MMP-9 and C-erbB2 were 37.84％ (28/74),59.46％ (44/74) and 48.65％ (36/74) in the breast cancer patients,the combined postive expression rate of these three kinds of markers was 64.86 ％ (48/74),which were higher than those in healthy controls group (x2=5.676,P＜0.05;x2=3.102,P＞0.05;x2=5.339,P＜0.05;x2 =2.310,P＞0.05),fibroadenoma of breast group (x2 =8.438,P＜0.01;x2 =4.491,P＜ 0.05;x2 =7.982,P＜0.01;x2 =4.844,P＜0.05) and non-breast cancer group (healthy controls group+ breast fibroadenoma group) (x2 =13.093,P＜0.01;xx2 =6.471,P＜0.05;x2 =11.837,P＜0.01;x2 =6.103,P＜ 0.05).The positive expression rates of individual hMAM and the joint detection in the breast cancer patients at stage Ⅲ + Ⅳ were higher than those in the patients at stage Ⅰ + Ⅱ;the positive expression rates of individual hMAM and combined with C-erbB2 were statistically significant (x2 =5.157,P＜0.05;x2 =4.912,P＜0.05).Conclusion:hMAM has a low positive rate in the diagnosis of micrometastases in the breast cancer patients,while hMAM combined with MMP-9 and C-erbB2 detection could improve the positive rates.which presents some clinical application value for the early diagnosis of breast cancer micrometastases.

Clinical significance and treatment regimen of sentinel lymph node microscopic metastasis in breast cancer / 中华普通外科杂志

Objective To explore the clinical significance and treatment regimen of sentinel lymph node(SLN) micrometastases and isolated tumor cell metastasis in breast cancer.Methods Ninety-seven breast cancer patients with sentinel lymph node micrometastases or isolated tumor cell metastasis from January 2013 to December 2015 were retrospectively studied.The patients were assigned to axillary lymph node dissection group (ALND,41 cases) and non axillary lymph node dissection group(non-ALND,56 cases) according to the final surgery mode to the axilla.Disease-free survival(DFS) and overall survival (OS) were compared between the two groups.Results Neither clinico-pathological factors,such as age,tumor size,grade,ER/PR status,HER-2 gene expression,Ki-67 expression and the size of the SLN metastasis,nor the treatment,such as breast surgery,postoperative adjuvant chemotherapy,radiotherapy and hormone therapy were found statistically different between the two groups (P ＞ 0.05).There were 96 patients evaluable with a median follow up of 24 months.The DFS of the ALND and non-ALND group was 97.5％ and 96.6％ (P ＞ 0.05),and the OS was 100％ and 98.2％ (P ＞ 0.05) respectively with no difference between the two groups.There were 2 ispilateral axillary recurrence in the non-ALND group and non in the ALND group.Conclusion Axillary lymph node dissection may be omitted for the breast cancer patients with sentinel lymph node micrometastases and isolated tumor cell metastases.But the postoperative adjuvant systemic treatment should be emphasized.

Predictors of Micrometastases in Patients with Barcelona Clinic Liver Cancer Classification B Hepatocellular Carcinoma

PURPOSE: Transarterial chemoembolization (TACE) is indicated for Barcelona Clinic Liver Cancer (BCLC) B hepatocellular carcinoma (HCC). Whether TACE provides any long-term survival benefits remains unclear. We aimed to investigate micrometastases predictors with which to identify patients who would benefit from surgical resection (SR). MATERIALS AND METHODS: First, we analyzed risk factors of micrometastases, microvascular invasion, and poor histologic grade in 38 patients with newly diagnosed resectable BCLC stage B HCC limited to one or two segments with well-preserved liver function and who underwent SR between January 2006 and December 2013. Second, we validated identified risk factors in 54 newly diagnosed resectable BCLC B HCC patients with well-preserved liver function who underwent TACE during the same period to determine their influence on survival. RESULTS: Risk factors of micrometastases in SR patients were α-fetoprotein (AFP) ≥110 [hazard ratio (HR)=5.166; 95% confidence interval (CI), 1.031–25.897; p=0.046] and prothrombin induced by vitamin K absence-II (PIVKA-II) ≥800 (HR=5.166; 95% CI, 1.031–25.897; p=0.046). The cumulative probability of tumor recurrence (p=0.009) after SR differed according to levels of AFP and PIVKA-II. After validation of these risk factors in the TACE group, patients with SR and AFP <110 and PIVKA-II <800 had superior survival outcomes than other patients (HR=0.116; 95% CI, 0.027–0.497; p=0.004). CONCLUSION: AFP and PIVKA-II levels predict micrometastases and survival. Therefore, they should be considered when selecting SR for BCLC B HCC.

Correlation between quantitative expression of T lymphoma invasion and metastasis inducing factor 1 mRNA and lymph node micrometastasis and prognosis in patients with colorectal cancer / 中华消化杂志

Objective To investigate the relationship between the changes of expression of T lymphoma invasion and metastasis inducing factor 1 (Tiam1) mRNA and lymph node micrometastasis and prognosis in patients with node-negative colorectal cancer(CRC).Methods From June 2008 to August 2010,a total of 63 patients with lymph node-negative CRC,20 patients with lymph node-positive CRC and 25 patients with colorectal benign lesions were enrolled.The relative quantity expression (RQ) of Tiam1 mRNA in CRC cancer tissues and colorectal benign lesions were detected by real-time quantitative polymerase chain reaction (PCR).The lymph node micrometastasis was determined by cytokeratin 20 detection in lymph nodes tissues.The five-year postoperative prognosis was evaluated by followed-up in the patients with lymph node-negative CRC.The correlation between the expression of Tiam1 mRNA and lymph node micrometastasis and prognosis was analyzed.The t-test,univariate analysis,multivariate analysis and Log-rank test were performed for statistical analysis.Results Lymphnode micrometastasis occurred in 33 from 63 patients with lymph node-negative CRC.The RQ of Tiam1 mRNA in the patients with lymph node-positive CRC was 9.84±-2.36,which was higher than that of patients with lymph node-negative CRC (5.15±3.58),and the difference was statistically significant (t=5.479,P＜0.01).The RQ of Tiam1 mRNA of these two groups were both higher than that of colorectal benign lesion (0.30± 0.21),and the difference was statistically significant(t=20.169,6.745;both P＜0.01).The RQ of Tiam1 mRNA of positive lymph node micrometastasis group was 6.30±1.95,which was higher than that of negative lymph node micrometastasis group (3.88 ± 1.63),and the difference was statistically significant (t=5.330,P＜0.01).In the patients with lymph node-negative CRC,the lower degree of tumor difference,the deeper invasion,the shorter survival time after surgery and postoperative recurrence and metastasis were related with the higher RQ of Tiam1 mRNA in tumor tissues (t=2.536,3.112,3.213,2.676;all P＜0.05).Univariate analysis revealed that the expression of Tiam1 mRNA in cancer tissues was correlated with lymph node micrometastases(x2=11.878,P =0.001).Multivariate analysis showed that it was an independent risk factors of lymph node micrometastases in CRC (relative risk:9.782).The five-year postoperative cumulative survival rate of high Tiaml mRNA expression group was 75.8 ％,which was lower than that of low expression group (97.1 ％),and the difference was statistically significant (x2 =4.575,P＜0.05).Conclusions Tiam1 may participate in the regulation of lymph node metastasis in CRC.Elevated expression of Tiam1 promotes lymph node metastasis and is closely relatived with poor prognosis of node-negative CRC,and which can be considered as an indicator of prognosis.

A Meta-analysis of the prognosis of sentinel node-positive breast cancer patients forgoing axillary lymph node dissection / 国际外科学杂志

Objective To compare the prognosis of sentinel node-positive breast cancer patients forgoing axillary lymph node dissection.Methods A systematic literature search (Medline,Embase,Cochrane Library)ended in April 2014 was performed to identify all eligible articles.Two reviewers independently screened and extracted data.RevMan5 was used for statistical analysis.Results A total of 1026 abstracts were retrieved and 18 clinical controlled studies finally included,the total number of patients were 47 894,7389 had micrometastases in sentinel lymph node,35 217 had macrometastases in sentinel lymph node and 5288 had positive sentinel lymph node regardless of micrometastases or macrometastases.For patients with MIC,the 5-year axillary recurrence rate,5-year disease free survival and 5-year overall survival had no significant difference between patients who only received sentinel lymph node biopsy and patients who received further axillary lymph node dissection,(OR =1.78;95％ CI:0.72-4.39,P=0.21),(OR =0.76,95％CI:0.56-1.04,P=0.08),(OR=0.77,95％CI:0.43-1.40,P=0.39).For patients with MAC,the 5-year axillary recurrence rate had no significant difference between patients who only received sentinel lymph node biopsy and patients who received further axillary lymph node dissection,(OR =1.21;95％ CI:O.76-1.91,P =0.42).For patients with positive sentinel lymph node regardless of micrometastases or macrometastases,the 5-year axillary recurrence rate and 5-year overall survival had no significant difference between patients who only received sentinel lymph node biopsy and patients who received further axillary lymph node dissection,(OR =1.29;95％ CI:0.92-1.80,P =0.14),(OR =0.96,95％ CI:0.64-1.45,P =0.84).Conclusions Among patients with limited positive SLN of breast cancer,patients forgoing ALND compared with ALND did not have obvious affect on long-term survival.

Immunohistochemical detection of axillary lymph node micrometastases in breast cancer patients: Increasing the accuracy of detection and decreasing labor intensive serial sectioning.

Background: The histological detection of axillary lymph node tumor metastases in cases of breast carcinoma is of major prognostic significance, but may be difficult when metastases are of microscopic size. The micrometastases can be detected either by immunohistochemistry (IHC) or serial sectioning. Aims: We investigated whether immunohistochemical techniques and serial sectioning can increase the accuracy of metastatic detection and compared the efficacy of both. Materials and Methods: Thirty cases of breast carcinoma were studied in all of whom the axillary lymph nodes had been reported as free of metastases. Blocks from these cases were serially sectioned and stained with hematoxylin and eosin and a single section was stained with monoclonal antibody to cytokeratin AE1/AE3 and epithelial membrane antigen. The positivity for micrometastases was correlated with size, number, grade and histological type of primary tumor, lymph node size and number. Results and Conclusion: In 5/30 previously unsuspected cases, micrometastases were revealed by IHC and in 1/30 by serial sectioning. These findings suggested that serial sectioning is a labor intensive, time consuming and impractical procedure. Micrometastases were more frequently detected with age of patient >50 years, Grade 2/3 tumor, tumor size >5 cm and more than one primary tumor. Immunohistochemical analysis can be recommended as a routine procedure or an adjunct to routine histological procedures for the correct staging of breast carcinoma and use of adjuvant chemotherapy, especially in the high risk group.

Impacto de las metástasis del linfonodo centinela y su tamaño, en el tratamiento del cáncer de mama / Impact of sentinel lymph node metastases in the treatment of breast cancer

Introducción: La importancia de las metástasis encontradas en linfonodos centinelas (LC) de pacientes con cáncer de mama ha sido cuestionada, por lo que frente al hallazgo de éstas, la observación sin disección axilar (DA), asociada a terapias adyuvantes, ha sido considerada como una alternativa en los últimos años. Objetivo: Evaluar las macro (MA), micro (MI) y submicrometástasis (SM) de cáncer de mama en LC, y su impacto en la DA posterior. Materiales y Métodos: Se revisaron los resultados de las biopsias de pacientes con cáncer de mama invasor con MA, MI y SM encontradas en el LC operadas en nuestra institución, entre mayo de 1999 y diciembre de 2011. Resultados: Se encontraron 134 pacientes con MA, 33 pacientes con MI y 30 SM, dentro de 632 pacientes con cáncer de mama invasor a los que se les realizó LC. De estos se operaron 130, 24 y 17 pacientes, respectivamente. La frecuencia de Linfonodos No Centinelas (LNC) con metástasis encontradas en la DA fue de 46,9 por ciento (61/130) para MA, 33,3 por ciento (8/24) para MI y 23,5 por ciento (4/17) para SM. Las metástasis del LNC provenientes de MA modificaron el TNM en 26,9 por ciento (35/130), las provenientes de MI en 20,8 por ciento (5/24) pacientes, mientras que las SM sólo lo modificaron en un paciente (5,9 por ciento). Conclusiones: La frecuencia del compromiso linfonodal en la DA es significativamente mayor en las pacientes con MA. El número de DA sin claro aporte terapéutico es alto y aumenta al disminuir el tamaño de las metástasis en el LC. Los resultados apoyan no realizar la DA en pacientes con MI y SM en el LC, que hayan recibido tratamiento quirúrgico conservador y vayan a recibir adyuvancia sistémica.

Introduction: The importance of sentinel lymph nodes (SL) metastasis at breast cancer patients has been questioned and observation without axillary dissection (AD) associated with adjuvant therapies has been the recommendation in recent years. Objective: To evaluate the macro (MA), micro (MI) and submicrometastasis (SM) of breast cancer in SL, and their impact on the posterior AD. Methods: We reviewed results of biopsies from patients with invasive breast cancer with MA, MI and SM found in the SL operated at our institution between May 1999 and December 2011. Results: We found 134 patients with MA, 33 patients with MI and 30 patients with SM, in a total of 632 patients with invasive breast cancer in those who underwent SL. These were operated 130, 24 and 17 patients respectively. The frequency of no sentinels lymph nodes (NSL) with metastases found on AD was 46.9% (61/130) for MA, 33.3% (8/24) for MI and 23.5% (4/17) for SM. The NSL metastasis from MA modified the TNM in 26.9% (35/130), those from MI in 20.8% (5/24) patients, while the SM only modified in one patient (5.9%). Conclusions: The frequency of lymph nodal involvement in AD is significantly higher in patients with MA. The number of AD without clear therapeutic input is high and increases with decreasing size of SL metastases. The results support to not perform AD in patients with MI and SM in the SL, who received conservative surgery and adjuvant therapy.

Micrometástasis: estrategias para su detección / Micrometastases: strategies for detection

La micrometástasis o enfermedad mínima residual ha adquirido una importancia trascendental en oncología al representar un verdadero problema clínico que debe ser solucionado, ya que aún se desconoce la respuesta de estos focos tumorales a los diferentes tratamientos que se usan para el control del cáncer. Aun cuando este es un problema específico fundamental a ser solucionado, ya existen métodos de ensayo inmunohistoquímicos y de biología molecular, que han permitido la ubicación de microfocos de células tumorales en diferentes órganos y tejidos, existiendo diferentes técnicas para determinar y cuantificar estas lesiones. Dentro de estas técnicas destacan la citometría de flujo y diferentes técnicas moleculares que van desde las ya tradicionales hasta las más nuevas y sofisticadas. El objetivo de la presente revisión está dirigido evaluar los nuevos métodos de diagnóstico que permitan la identificación de esta enfermedad residual, lo cual serviría para establecer tratamientos individualizados que pudieran prevenir la recurrencia de la enfermedad en los pacientes de cáncer bajo tratamiento.

Micrometastasis or minimal residual disease has become critically important in oncology since it represents a true clinical problem that must be solved, as the response of these tumor foci to the different treatments that are used for the control of cancer, is still unknown. Even though this is a fundamental specific problem to be solved, there are already immunohistochemical and molecular biology diagnostic methods that have allowed microfoci location of tumor cells in various organs and tissues, and different techniques are available to determine and quantify these lesions. Within these techniques, flow cytometry and different molecular methods are included, and they range from the traditional to the newest and most sophisticated. The goal of this review was aimed to evaluate new diagnostic methods that permit the identification of this residual disease, which would serve to establish individualized treatments and prevent the recurrence of the disease in cancer patients under treatment.

Research prowess of pancreatic cancer with lymph node micrometastases / 中华消化外科杂志

As one of the gastrointestinal malignancies,pancreatic cancer is well known because of high degree of malignancy,low survival rate and very poor prognosis.Lymphatic metastasis,the most important metastasis of pancreatic cancer,has the characteristics of metastasis in an early stage and high occurrence rate.Recently,some studies have suggested that widespread micrometastasis of lymph nodes occurring in the early stage of pancreatic cancer could play an important role in influencing postoperative neoplasm recurrence.Further studies on lymph node micrometastasis of pancreatic cancer are needed to help to understand pancreatic cancer more deeply and to comprehend metastasis rule more clearly.So we can choose more reasonable surgical treatment for every patient,achieving individual treatment,so as to improve the prognosis of the pancreatic cancer patients.

Impact on Prognosis of Lymph Node Micrometastasis and Isolated Tumor Cells in Stage II Colorectal Cancer

PURPOSE: Even though the importance of micrometastases (MMS) and isolated tumor cells (ITC) has been brought up by many physicians, its impact on the prognosis in stage II colorectal cancer is uncertain. In this research, we tried to investigate the clinical features of MMS and ITC and to prove any correlation with prognosis. METHODS: The research pool was 124 colorectal cancer patients who underwent a curative resection from April 2005 to November 2009. A total of 2,379 lymph nodes (LNs) were examined, and all retrieved LNs were evaluated by immunohistochemical staining with anti-cytokeratin antibody panel. Clinicopathologic parameters and survival rates were compared based on the presence of MMS or ITC and on the micrometastatic lymph node ratio (mmLNR), which is defined as the number of micrometastatic LNs divided by the number of retrieved LNs. RESULTS: Out of 124 patients (26.6%) 33 were found to have MMS or ITC. There were no significant differences in clinicopathologic features, such as gender, tumor location and size, depth of invasion, histologic grade, except for age (P = 0.04). The three-year disease-free survival rate for the MMS or ITC positive group was 85.7%, and that for MMS and ITC negative group was 92.8% (P = 0.209). The three-year disease-free survival rate for the mmLNR > 0.25 group was 73.3%, and that for the mmLNR < or = 0.25 group was 92.9% (P = 0.03). CONCLUSION: The presence of MMS or ITC was not closely correlated to the prognosis. However, mmLNR is thought to be a valuable marker of prognosis in cases of stage II colorectal cancer.

Hot spots of sentinel node biopsy in breast cancer / 肿瘤研究与临床

Sentinel lymph node biopsy represents the state of the art of breast surgery, but its widely application might surpass the support of available evidences. The hot spots of sentinel lymph node biopsy in breast cancer include the prognosis of micrometastases in sentinel nodes, the prediction of non-sentinel nodes metastases in positive sentinel nodes patients, and the intraoperative molecular diagnosis of sentinel nodes.These are discussed accompanying with the updated results from the 31st SABCS held in December, 2008.

Prediction value of micrometastases detection in rib marrow on distant metastases with non-small lung cancer / 肿瘤研究与临床

Objective To evaluate the prediction value on distant metastases of fib bone marrow micrometastases (BMM) of patients with non-small lung cancer ( NSCLC ). Methods From January 2003 to March 2006, 168 patients undergoing surgical treatment for NSCLC were prospectively investigated for the presence of BMM by using immnnohistochemistry. The sensitivity and specificity of the rib bone marrow micrometastases technique were also calculated. Receiver operating characteristic curve (ROC curve)was drawn according to data. Results Occult BMM were detected in 29.76 %(50/168) of patients with NSCLC. 15(29.76 %) patients developed metastases in the 50 patients with BMM and 15 (12.71%) patients developed metastases in the 118 patients without BMM. The sensitivity and the specificity of the technique was 61.54 % and 79.84 %. The false negative rate was 38.46 % and the false positive rate was 20.16 %. The positive predictive value, negative predictive value and Youden' s index were 87.5 %, 93.33 %, 74.33 % respectively. Conclusion The detection of BMM could predict the distant metastases of non-small lung cancer patients through receiver operating characteristic curve evaluation, however, the detecting sensitivity should be improved.

A study of intratumor microvessel density and lymph node micrometastasesof pN0 supraglottic laryngeal squamous cell carcinoma / 临床耳鼻咽喉头颈外科杂志

Objective:To investigate the correlation between intratumor microvessel density (IMVD) and lymph node micrometastases. Method: IMVD and lymph node micrometastases were stained with CD105 and CK19 antibody by immunohistochemical method of SABC respectively. Result:IMVD marked with CD105 antibody corre-lated with T stage and lymph node micrometastases(P<0.01). Conclusion: The result show that IMVD marked with CD105 antibody highly correlated with lymph node micrometastases. It could be a index to evaluate the prog-nosis of patients with pN_0 supraglottic laryngeal squamous cell carcinoma.

Las células prostáticas en la circulación sanguínea en pacientes con cáncer prostático expresan la proteína P504S: un estudio utilizando inmunocitoquímica / Circulating prostate cells in patients with prostate cancer express P504S: an immunocytochem

Determinar la presencia de células prostáticas en la circulación sanguínea (CPCs) en pacientes con cáncer prostático y la expresión de P504S. Método: Las células mononucleares fueron separadas de la sangre venosa por centrifugación diferencial, e identificadas utilizando anticuerpos monoclonales contra APE y P504S. Diez mujeres fueron usadas como controles. 66 hombres con cáncer prostático formaron el grupo de estudio. Resultados: 69,7 por ciento tuvieron células prostáticas en la sangre venosa, todas las células detectadas fueron positivas para la expresión de P504S. Conclusiones: La detección de células prostáticas P504S positivas en biopsias de la próstata esutilizando para el diagnóstico de cáncer, células benignas no se expresan el antígeno. Este es el primer estudio que demuestra la expresión de P504S en CPCs, con la inferencia que estas células son malignas.

To determine the expression of P504S en circulating prostate cells (CPCs) in men with prostate cancer. Method: Mononuclear cells were separated from venous blood using differential centrifugation andidentified using monoclonal antibodies against PSA and P504S. 10 women were used as controls and 66 men with prostate cancer formed the study group. Results: 69.7 percent of men were positive for CPCs, all the CPCs detected expressed the antigen P504S. Conclusions: The detection of P504S positive cells in prostate biopsies is used to determine whether they are malignant or not, benign cells are P504S negative. This is the first study to show that CPCsare P504S with the implication that they are malignant cells.

Intraoperative Examination of Sentinel Lymph Nodes by Rapid Immunohistochemistry in Breast Cancer

PURPOSE: The recently developed method of rapid immunohistochemistry (IHC) was applied to the intraoperative examination of sentinel lymph node (SLN) because as their routine frozen-section examination is liable to yield a false-negative results. This study is devoted to establish a reliable protocol for rapid IHC of SLN. METHODS: Between August 2004 and April 2005 a retrospective study was performed. SLNs from 50 breast cancer patients with clinically negative SLN were examined intraoperatively using hematoxylin-eosin (H&E) stain and immunostain for cytokeratin by rapid IHC assay. After examination of the frozen section, the SLNs were paraffin embedded and serially sectioned at 5 micrometer intervals. RESULTS: The median age and tumor size of the patients was 61.0 years and 1.4 cm (6% Tis, 70% T1, and 24% T2), respectively. The total number of dissected SLN was 112, with a mean of 2.2 (range, 1~4) SLNs per patient. Seven SLNs were found to be positive from metastasis in permanent pathological sections. Of these, 5 were stained by both intraoperative rapid IHC and H&E stain while one was not stained at all. The remaining SLN was initially stained with only the rapid IHC assay. The mean turn around time of the rapid IHC was less than 20 minutes, with sensitivity, true negative value, true positive values and accuracy of 85.7, 99.1, 100, and 99.1% respectively. CONCLUSIONS: The rapid IHC was a very sensitive and rapid technique for the intraoperative detection of metastatic involvement of SLNs, whitch may be helpful at increasing the accuracy of detecting the micro-metastasis of sentinel lymph nodes during an operation.

Clinicopathological study of lymph node micrometastasis in patients with early gastric cancer / 上海第二医科大学学报

Objective To study the relationship between lymph node micrometastasis in early gastric cancer and clinicopathology of tumor,and explore an appropriate operative procedure.Methods A total of 1 004 lymph nodes from 50 patients with early gastric cancer(EGC)were sliced and restained with H.E and immunohistochemical technique,respectively.Immunohistochemical staining was performed by the streptavidin-biotin immunoperoxidase method with cytokeratin-specific monoclonal antibody CAM5.2.The relationship between lymph node micrometastasis and clinicopathological characteristics of primary tumors and prognosis of EGC was analysed.Results The incidence of nodal micro-involvement was significantly increased in diffuse type cancerous lesions(n=11,32.35%)as compared with intestinal type cancerous lesions(n=1,6.25%)(P

Detection and therapy of micrometastasis in carcinoma of bladder / 肿瘤研究与临床

Micrometastasis are frequently accompanied by the majority of cases of invasive malignant tumor, being a compacted relationship with the prognosis of patients. We should pay more attentions to the occurrence of micrometastasis in the diagnosis and management of carcinoma of urinary bladder, which is the most commonly diagnosed malignancy in urinary system and a significant cause of morbidity and mortality.This article introduces the diachronic concept of micrometastasis and the major methods for the detections of micrometastasis, moreover,it reviews recent advances about the detection of micrometastasis in bladder cancer, and about the benefits that patients of the disease might have received in the treatment of micrometastasis.

Detection and clinical significance of micrometastases in non-small cell lung cancer / 医学研究生学报

Non-small cell lung cancer has a poor prognosis. Many patients who were proved to have none lymph node metastasis still relapse after operation. It may be caused by micrometastases which can′t be detected by conventional pathologic technique. Recently immunocytochemistry and moleculer methods are used to detect micrometastases in the peripheral blood, bone marrow or lymph node near the tumor. But the standard and reliable methods need to be developed and the clinical significance of micrometastases need to be discussed.