Impact of Lymph Node Micrometastasis in Patients with Pancreatic Head Cancer

Purpose The purpose of this study was to investigate the clinical significance of nodal micrometastasis in patients who underwent a curative operation for pancreatic cancer. Experimental Design Fifty-eight patients underwent a macroscopically curative resection with extended lymph node dissection for pancreatic cancer. The total number of resected lymph nodes was 1,058, and 944 histologically negative lymph nodes were subjected to immunohistochemical staining to detect occult micrometastases. Results Nodal micrometastases were detected immunohistochemically in 147 out of 944 resected histologically negative lymph nodes (15.6%). Forty-four of all 58 patients (75.9%) and 13 of the 23 histologically node-negative patients (56.5%) had nodal micrometastases. Nodal micrometastases existed in the N1 lymph node area most frequently, followed by the N2 and N3 lymph node areas. The distribution was similar to that of histologically metastatic lymph nodes. Ten out of 16 patients (62.5%) with histological N1, and 5 out of 16 patients (31.3%) with histological N2 had nodal micrometastases beyond the histological lymph node status. Three and 5-year survival rates of pN0 patients without lymph node nodal micrometastases were both 60.0%, while those with nodal micrometastases were 19.2% and 0%, respectively. There was statistically significant difference between the both groups (P = 0.041). Conclusions Nodal micrometastasis in pancreatic cancer existed in wider and more distant areas than histological lymph node status, and it was an unfavorable predictive factor, even in N0 patients.     

Occult Micrometastases in Axillary Lymph Nodes Predict Subsequent Distant Metastases in Stage I Breast Cancer: A Case-Control Study with 15-Year Follow-Up

Background The prognostic significance of occult axillary metastases was evaluated in patients with stage I breast cancer.Methods Ninety-six patients with pT1 breast carcinoma who underwent axillary lymph node dissection had negative nodes in routine microscopic examination. Forty-eight patients developed distant metastases within 15 years after surgery (M group) and are compared to 48 age-matched patients who were disease-free for 15 years (NM group). We reexamined 1539 lymph nodes from these patients, using three levels and cytokeratin immunostain.Results Occult metastases were detected in 21 patients: 16 of 48 (34%) in the M group and 5 of 48 (11%) in the NM group (P = .007). All metastases measured 2.0 mm or less and were classified as micrometastases (>0.2 mm to 2.0 mm) in 11 cases and as individual tumor cells (individual cells or clusters measuring 0.2 mm) in 10 cases. Micrometastases were 10 times more frequent in the M group than in the NM group (10/48 vs. 1/48; P = .004). Although there was no difference in tumor size, histologic type, estrogen receptor status, or type of treatment between the two patient groups, tumors in the M group were of a higher grade, had higher mitotic index and showed lymphovascular invasion. In multiple logistic regression, only high mitotic index and presence of micrometastases showed an independent significant correlation with the subsequent occurrence of distant metastases.Conclusions The presence of micrometastases (>0.2 to 2.0 mm) in axillary nodes is significantly associated with the development of distant metastases in patients with T1 breast cancer.     

Immunohistochemically demonstrated lymph node micrometastasis and prognosis in patients with gallbladder carcinoma

OBJECTIVE: To investigate whether immunohistochemically demonstrated lymph node micrometastasis has a survival impact in patients with advanced gallbladder carcinoma (pT2-4 tumors). SUMMARY BACKGROUND DATA: The clinical significance of immunohistochemically detected lymph node micrometastasis recently has been evaluated in various tumors. However, few reports have addressed this issue with regard to gallbladder carcinoma. METHODS: A total of 1476 lymph nodes from 67 patients with gallbladder carcinoma (pN0, n = 40; pN1, n = 27) who underwent curative resection were immunostained with monoclonal antibody against cytokeratins 8 and 18. The results were correlated with clinical and pathologic features and with patient survival. RESULTS: Lymph node micrometastases were detected immunohistochemically in 23 (34.3%) of the 67 patients and in 37 (2.5%) of the 1476 nodes examined. Of the 37 nodal micrometastases, 21 (56.8%) were single-cell events, and the remaining 16 were clusters. Five micrometastases were detected in the paraaortic nodes. Clinicopathologic features showed no significant associations with the presence of lymph node micrometastases. Survival was worse in the 27 patients with pN1 disease than in the 40 with pN0 disease (5-year survival; 22.2% vs. 52.6%, P = 0.0038). Similarly, survival was worse in the 23 patients with micrometastasis than in the 44 without micrometastasis (5-year survival; 17.4% vs. 52.7%, P = 0.0027). Twenty-eight patients without any lymph node involvement had the best prognosis, whereas survival for the 11 patients with both types of metastasis was dismal. The grade of micrometastasis (single-cell or cluster) had no effect on survival. The Cox proportional hazard model identified perineural invasion, lymph node micrometastasis, and microscopic venous invasion as significant independent prognostic factors. CONCLUSIONS: Lymph node micrometastasis has a significant survival impact in patients with pN0 or pN1 gallbladder carcinoma who underwent macroscopically curative resection. Extensive lymph node sectioning with keratin immunostaining is recommended for accurate prognostic evaluation for patients with gallbladder carcinoma.     

Lymph node micrometastases do not predict relapse in stage II colon cancer

Background: Over one third of patients with stage II colonic adenocarcinoma experience tumor recurrence. Because effective adjuvant therapy is now available, it is important to identify subsets of patients at higher risk for relapse who may benefit from early treatment. Immunohistochemistry has been used to detect microscopic metastases in histologically uninvolved mesenteric lymph nodes, but the prognostic significance of minimal nodal involvement has not been established. Methods: Hematoxylin and eosin (H&E)-stained recuts of 900 mesenteric lymph nodes from 55 patients (range, 2–47; mean, 16.4 nodes per case) with resected pT3 or pT4, N0, M0 (TNM stage II) colonic adenocarcinomas were re-examined for the presence of metastases and then stained immunohistochemically for keratin using the AE1:AE3 antibody. Twenty-seven patients did not experience recurrence of tumor within 5 years following resection (no evidence of disease [NED]); 28 patients relapsed during the same time frame. Lymph nodes from 10 patients having colonic resections for nonneoplastic disorders also were stained as controls. Keratin-positive cells and cell clusters were quantified in the lymph nodes, and comparisons were made between patients with and without tumor relapse. Results: In the relapse group, four patients had positive nodes already identified on the H&E-stained recuts and had to be excluded from further analysis. Sixteen additional patients had keratin-positive cells; thus, 16 of 24 (67%) had micrometastases. In the NED group, one patient had a positive node on H&E staining and 22 additional patients had keratin-positive cells, so 22 of 26 (84%) patients had micrometastases. In the patients who had micrometastases, there was a mean of 3.5 and 4.6 positive nodes in the relapse and NED groups, respectively, and a mean of 11.3 and 12.4 keratin-positive cells or clusters in the relapse and NED groups, respectively. No keratin-positive cells were found in the 1 to 21 (mean, 9.1) nodes per case studied in the control patients. Conclusions: Micrometastases to histologically uninvolved mesenteric lymph nodes commonly are detected in patients with pT3 or pT4 colonic adenocarcinomas on recuts stained immunohistochemically for keratin. Nodal micrometastases detected by immunohistochemical staining are not useful for identifying stage II patients at higher risk for relapse. Presented at the annual meeting of the Society of Surgical Oncology, March 16–19, 2000, New Orleans.     

Immunohistochemically demonstrated lymph node micrometastasis and prognosis in patients with otherwise node-negative hilar cholangiocarcinoma

OBJECTIVE: To investigate whether immunohistochemically demonstrated lymph node micrometastasis has prognostic significance in patients with histologically node-negative (pN0) hilar cholangiocarcinoma. SUMMARY BACKGROUND DATA: The clinical significance of immunohistochemically detected lymph node micrometastasis recently has been evaluated in various tumors. However, no reports have addressed this issue with regard to hilar cholangiocarcinoma. METHODS: A total of 954 lymph nodes from surgical specimens of 45 patients with histologically node-negative hilar cholangiocarcinoma who underwent macroscopically curative resection were immunostained with monoclonal antibody against cytokeratins 8 and 18. The results were examined for relationships with clinical and pathologic features and with patient survival. RESULTS: Lymph node micrometastases were detected immunohistochemically in 11 (24.4%) of the 45 patients, being found in 13 (1.4%) of 954 lymph nodes examined. Of the 13 nodal micrometastases, 11 (84.6%) were found in the N2 regional lymph node group rather than N1. Clinicopathologic features showed no associations with lymph node micrometastases. Survival curves were essentially similar between patients with and without micrometastasis. In addition, the grade of micrometastasis showed no effect on survival. The Cox proportional hazard model identified microscopic venous invasion, microscopic resection margin status, and histologic differentiation as significant prognostic factors in patients with pN0 disease. CONCLUSIONS: Lymph node micrometastasis has no survival impact in patients with otherwise node-negative hilar cholangiocarcinoma. The authors do not recommend extensive lymph node sectioning with keratin immunostaining for prognostic evaluation.     

A、B期直肠癌淋巴结微转移的研究

目的　研究A、B期直肠癌淋巴结微转移的特点 ,分析微转移与各种临床病理因素及预后的关系。方法　选用鼠抗人细胞角蛋白 2 0 (CK2 0 )单克隆抗体 ,运用免疫组化方法 ,检测 5 7例A、B期直肠癌根治标本的直肠周围淋巴结 183个 ,并进行统计学处理。结果　 2 5例 ( 4 3 .9% )直肠癌的 48个淋巴结 ( 2 6.2 % )出现微转移。淋巴结微转移与原发肿瘤的大小、分化程度、肿瘤的部位有关 ,但与年龄、性别及原发肿瘤侵入的深度无关。随访平均 42个月结束后 ,有微转移的直肠癌患者生存率 ( 74.9% )与无微转移的直肠癌患者 ( 78.8% )无明显差异。结论　直肠癌微转移可能增加局部复发或远处转移的发生 ,但对预后无明显关系     

Distribution of Lymph Node Metastasis Including Micrometastasis in Gastric Cancer with Submucosal Invasion

Abstract The purpose of this retrospective study was to analyze the distribution of lymph node metastases, including micrometastases, according to the location of the gastric cancer with submucosal invasion. A total of 118 patients with submucosal gastric cancer were enrolled in this study. The distribution of lymph node metastases was examined according to tumor location. Immunohistochemical examination using anti-cytokeratin antibody was performed to examine nodal micrometastases in 118 patients. Lymph node metastasis was found in 19.5% (23/118) of the patients. Significant differences were found for tumor size and depth, lymphatic invasion, and venous invasion for patients with and without nodal metastasis. The distribution of lymph node metastasis for tumors at upper or middle portions of the stomach was mainly found along the left gastric artery. The distribution of lymph node metastasis for tumors in the lower and lesser curvature varied. Immunohistochemical analysis found that 15 of 23 patients with lymph node metastasis found by histologic examination had micrometastases. The presence of two or more lymph node micrometastases was found in these 15 patients, and they were distributed in another stations, including distant nodes. The incidence of micrometastasis was 24.2% (23/95) in pN0 patients. Lymph node micrometastases were confined to regional nodes near the primary tumor. When planning minimally invasive treatment for submucosal gastric cancer, it is important to understand the distribution of lymph node metastasis, including micrometastasis, according to tumor location.     

Immunohistochemically Detected Lymph-Node Micrometastases in Breast Cancer and their Correlation with Prognostic Factors

Abstract: The prognostic value of immunohistochemically detected micrometastases (N1a-IHC) in conventionally negative lymph nodes (N₀) and its association with newer prognostic factors is controversial.
Axillary lymph nodes ( n = 2,528) of 159 patients with pT1–T N₀ M₀-breast cancer were examined for micrometastases using a monoclonal cytokeratine antibody. In addition to the histological findings, estrogen and progesterone receptors (ER, PR), S-Phase, ploidy, EGF-R, p53, Ki-67, HER-2/neu oncoprotein, cathepsin D, and p52 were investigated. The mean follow up time was 51 ± 16 months.
Micrometastases were detected in 53 of 2,528 (2.1%) lymph nodes. In 18 of 159 patients (11.3%) staged as N₀ by conventional histology, one or more micrometastases were detected immunohistochemically. These patients have a prognostic disadvantage compared with N₀-IHC-patients significant for distant metastases-free survival; (p =.003) and for overall survival (p =.006). Differences (p <.05) between N₀-IHC- and N1a-IHC-tumors were found in tumor size, ER, EGF-R, and cathepsin D. Tumor size, grading "3," and peritumoral vessel invasion, but not the detection of micrometastases, were confirmed as independent prognostic factors in node-negative patients by multivariate Cox regression analysis.
Immunohistochemically detected micrometastases in axillary lymph nodes are of prognostic importance. However, they are not independent prognostic factors, because a correlation with other prognostic factors has been proven.     

The Impact of Lymph Node Metastases on Survival in Extremity Soft Tissue Sarcomas

Background The impact of lymph node metastases on survival in extremity soft tissue sarcomas has been studied for a long time with controversial results. The purpose of this study was to compare survival of patients with initial lymph node metastases with those having lymph node or distant metastases or both after initial curative surgery. Methods Patients treated between 1995 and 2000 for extremity soft tissue sarcoma were retrospectively studied in four groups: those with metastatic regional lymph nodes at the time of diagnosis, those with only regional lymph node recurrences, those with only distant metastatic relapses, and those with both regional lymph node recurrences and distant metastatic relapses, all of the last three groups after initial curative surgery. The impact of timing of lymph node metastases on disease-free and overall survival was evaluated. Results A total of 110 patients (73 men) with a median age of 45 years were eligible for the study. Three-year disease-free survival was significantly longer in patients with initial regional lymph node metastases than in patients with only lymph node recurrences after curative surgery (p = 0.04) and patients with initial (p = 0.0002) and recurrent (p = 0.0004) regional lymph node metastases had longer disease-free survival than patients with distant metastases. Overall survival difference between patients with initial regional lymph node metastases and patients with only lymph node recurrences after curative surgery was significant at 5 years (p = 0.01). Conclusions It is logical to separate patients with initial lymph node metastases from those with distant metastases in staging and to treat patients with initial lymph node metastases with radical surgical interventions if complete tumor resection seems feasible.     

The immunohistochemical assessment of occult regional lymph node metastases in patients with T3pN0M0 prostate cancer before definitive radiotherapy

OBJECTIVE: To detect occult regional lymph node metastases in patients with T3pN0M0 prostate cancer not recognized by routine haematoxylin and eosin staining, and to evaluate the clinical relevance of this finding. PATIENTS AND METHODS: Formalin-fixed and paraffin-embedded pelvic lymph nodes (1118) from 92 patients were evaluated by immunohistochemistry using antibodies for prostate specific antigen (PSA) and pancytokeratin (AE1/AE3). Of the tumours, 14% were well, 69% moderately and 17% poorly differentiated. The extent of tumour was categorized as T3pN0M0 in all patients, who were referred for definitive radiotherapy after pelvic staging lymphadenectomy. The median (range) serum PSA value before treatment was 18.5 (0.4-342) microg/L. After radiotherapy, the patients were followed by assessing biochemical progression, pelvic recurrence and/or development of distant metastases. The median (range) observation time for all patients was 61 (16-136) months. RESULTS: Occult lymph node metastases were detected in four (4.4%) of the 92 patients. Patients with or without occult metastases had similar serum PSA levels and histological grades. None of the four patients with occult metastases progressed, compared with 37 of the 88 (42%) with no such metastases. CONCLUSION: Using immunohistochemistry the detection rate of occult lymph node metastases in patients with T3pN0M0 prostate cancer is low. The occurrence of such metastases is probably unrelated to the serum PSA value before treatment. The short-term outcome of patients subsequently treated with definitive radiotherapy does not seem to be associated with the finding of occult lymph node metastases, but long-term follow-up is needed. So far, the results do not justify the search for occult lymph node metastases as a routine procedure in these patients     

Disease progression and survival of patients with positive lymph nodes after radical prostatectomy. Is there a chance of cure?

PURPOSE: In prostate cancer involvement of regional lymph nodes is regarded as a poor prognostic factor. Is this also true for micrometastasis if a meticulous lymph node dissection is performed? We determined progression rate and survival of patients with positive nodes following radical prostatectomy according to the number of metastases. MATERIALS AND METHODS: Between 1989 and 1999, 367 patients with clinically organ confined prostate cancer underwent meticulous pelvic lymph node dissection and radical prostatectomy. None of the patients received immediate adjuvant therapy. RESULTS: Of the patients 92 (25%) had histologically proven lymph node metastases. Followup of more than 1 year was available in 88 patients (96%), and median followup was 45 months (range 13 to 141). Of 19 patients (22%) who died of prostate cancer 16 had more than 1 positive node. Of the 39 patients with only 1 positive node 15 (39%) remained without signs of clinical or chemical progression. Whereas of the 20 and 29 patients with 2 or more positive lymph nodes only 2 (10%) and 4 (14%), respectively, remained disease-free. Time to prostate specific antigen relapse, symptomatic progression and tumor related death were significantly affected by the number of positive nodes. CONCLUSIONS: Meticulous lymph node dissection reveals a high rate of metastases (25%). In patients with positive nodes time to progression is significantly correlated with the number of diseased nodes. Some patients with minimal metastatic disease remain free of prostate specific antigen relapse for more than 10 years after prostatectomy without any adjuvant treatment. Meticulous pelvic lymph node dissection, particularly in patients with micrometastases, seems not only to be a staging procedure, but may also have a positive impact on disease progression and long-term disease-free survival.     

Lymph node isolated tumor cells and micrometastases in pathological stage I non-small cell lung cancer: prognostic significance

Objective: To determine the prevalence and prognostic significance of lymph node micrometastases and isolated tumor cells (ITC) in patients submitted for radical resection for pathological stage I non-small cell lung cancer (NSCLC). Methods: From January 1998 through December 2005, 87 consecutive pT1-2, pN0 NSCLC patients were enrolled. Surgical specimens were submitted to pathological routine examinations to define histotype, grade, stage, vascular invasion, necrosis and tumor proliferative index. A total of 694 regional lymph nodes were examined by means of serial sections stained with hematoxylin and eosin and labelled by immunohistochemistry (antibody AE1/AE3, DAKO). Relationships between these parameters and patients’ prognosis were investigated. Results: By histological examination, there were 36 squamous-cell carcinoma, 38 adenocarcinoma and 13 large-cell carcinoma. Micrometastases and ITC were detected in 19 lymph nodes (2.7%) of 14 patients (16%). Significant correlation was observed between micrometastases or ITC and adenocarcinoma (p = 0.03) and the absence of necrosis (p = 0.05). No relationship was demonstrated between micrometastases or ITC and T-status, vascular invasion or proliferative index (p > 0.05). Median follow-up was 3.2 (range 0.25–8.6) years. Two- and 5-year disease-free survival was similar for patients with and without micrometastases or ITC (79% and 64% vs 81% and 64%, respectively). Recurrence occurred in three patients with (two local, 66%) and in 21 patients without micrometastases or ITC (three local, 14%) (p = 0.186). By multivariate analysis only T-status was demonstrated to be a significant prognostic factor. Discussion: Micrometastases or ITC to regional lymph nodes are demonstrated to be not a rare aspect of pathological stage I resected lung cancer. In our series, the presence of lymph nodes micrometastases does not affect long-term disease-free survival.     

Sentinel lymphonodectomy and S-classification: A successful strategy for better prediction and improvement of outcome of melanoma

The most successful strategies in the management of melanoma have always been based on early diagnosis and timely surgical removal. Sentinel lymphonodectomy (SLNE) is the most reliable technique for the detection of melanoma micrometastases in regional lymph nodes. The micromorphometric S-classification, a routinely determinable surrogate of tumor burden in the sentinel lymph node (SLN), has high prognostic relevance. SIII metastases, defined by a depth of invasion (d) greater than 1 mm below the capsular level, imply a risk of more than 50% for the presence of nonsentinel lymph node metastases in the same basin and for the emergence of distant metastases within 5 years of follow-up. Corresponding risk with SI metastases (d≤0.3 mm) and SII metastases (0.3 mm<d≤1 mm) do not exceed 15%. The survival curve for patients with SIII metastases approaches that of patients in the pre-SLNE era who underwent delayed lymph node dissection for subsequently detected nodal macrometastases. The survival of patients with initially removed SI and SII metastases is much better, similar to that of patients with S0 metastases. This explains the significant survival benefit of SLN-guided surgery in the entire population of patients with melanomas thicker than 0.75 mm, although the outcome of the subgroup without nodal metastases is not influenced by SLNE.     

前列腺癌根治术前盆腔淋巴结微转移检测的研究

目的 明确新辅助治疗后前列腺癌根治术前,real-time PCR检测盆腔淋巴结微转移的意义.方法 2007年8月至2010年3月对21例临床局限性前列腺癌病例,根据病理检查阳性(A组)、real-time PCR检查前列腺特异性抗原(PSA)mRNA和前列腺特异性膜抗原(PSMA)mRNA阳性(B组)、病理检查及real-time PCR检查PSA mRNA及PSMA mRNA均阴性(C组)进行分组,D组为对照组.术前行淋巴管造影显示盆腔淋巴结,对可疑淋巴结在X线定位下穿刺抽吸淋巴液,用real-time PCR方法检测淋巴液中PSA mRNA和PSMA mRNA的表达,阳性表达提示淋巴结转移的存在,术后对淋巴结组织切片进行免疫组化检查.结果 对术前盆腔淋巴结穿刺抽吸淋巴液用real-time PCR方法检测PSA mRNA和PSMA mRNA的表达,证实有14例淋巴结存在微转移,术后对清扫淋巴结进行免疫组化检查有3例存在淋巴结转移,A组与B组PSA mRNA和PSMA mRNA的表达存在明显的差异;A、B组淋巴液中PSA mRNA及PSMA mRNA的表达明显高于淋巴结(P＜0.01).结论 采用real-time PCR方法检测淋巴液中PSA和PSMA mRNA的表达有利于探测到淋巴结微转移的存在,术前穿刺淋巴结抽吸淋巴液提高了术前前列腺癌分期的准确性.     

Characteristics of the sentinel lymph node in breast cancer predict further involvement of higher-echelon nodes in the axilla: a study to evaluate the need for complete axillary lymph node dissection

BACKGROUND: Sentinel lymph node (SLN) biopsy techniques provide accurate nodal staging for breast cancer. In the past, complete lymph node dissection (CLND) (levels 1 and 2) was performed for breast cancer staging, although the therapeutic benefit of this more extensive procedure has remained controversial. HYPOTHESIS: It has been demonstrated that if the axillary SLN has no evidence of micrometastases, the nonsentinel lymph nodes (NSLNs) are unlikely to have metastases. OBJECTIVE: To determine which variables predict the probability of NSLN involvement in patients with primary breast carcinoma and SLN metastases. METHODS: An analysis of 101 women with SLN metastases and subsequent CLND was performed. Variables included size of the primary tumor, tumor volume in the SLN, staining techniques used to initially identify the micrometastases (cytokeratin immunohistochemical vs hematoxylin-eosin), number of SLNs harvested, and number of NSLNs involved with the metastases. Tumor size was determined by the invasive component of the primary tumor. Patients with ductal carcinoma in situ who were upstaged with cytokeratin staining were considered to have stage T1a tumors. RESULTS: Sentinel lymph node micrometastases (<2 mm) detected initially by cytokeratin staining were associated with a 7.6% (2/26) incidence of positive CLND compared with a 25% (5/20) incidence when micrometastases were detected initially by routine hematoxylin-eosin staining. Sentinel lymph node micrometastases, regardless of identification technique, inferred a risk of 15.2% (7/46) for NSLN involvement. As the volume of tumor in the SLN increased (ie, <2 mm, >2 mm, grossly visible tumor), so did the risk of NSLN metastases (P<.001). CONCLUSIONS: Our study demonstrated that patients with micrometastases detected initially by cytokeratin staining had low-volume disease in the SLN with a small chance of having metastases in higher-echelon nodes in the regional basin other than the SLN. Characteristics of the SLN can provide information to determine the need for a complete axillary CLND. Complete lymph node dissection may not be necessary in patients with micrometastases detected initially by cytokeratin staining since the disease is confined to the SLN 92.4% of the time. However, the therapeutic value of CLND in breast cancer remains to be determined by further investigation.     

Genetic detection of lymph node micrometastases: a selection criterion for liver transplantation in patients with liver metastases after colorectal cancer

BACKGROUND: Liver transplantation for nonresectable liver metastases from colorectal cancer was abandoned in 1994 on account of high recurrence rates. The aim of this study was to investigate whether the genetic detection of micrometastases in histologically negative lymph nodes of the primary colon cancer could be applied to select patients for liver transplantation. METHODS: We analyzed 21 patients with colorectal cancer who had undergone liver transplantation between 1983 and 1994 for liver metastases. Eleven patients were histologically lymph node negative at the time of surgery; ten patients with lymph node metastases served as control group. DNA sequencing was used to screen tumor material for p53 and K-ras mutations. Mutant allele-specific amplification (MASA) was then used to search for micrometastases in DNA from regional lymph nodes of the primary colorectal cancer. RESULTS: p53 and K-ras mutations were detected in 12 (57%) and 3 (14%) of 21 patients in the colorectal cancer, respectively. The mutations were confirmed in the corresponding liver metastases. Of 11 patients with histologically negative lymph nodes, nine were eligible for MASA due to presence of p53 or K-ras mutation. MASA revealed six of nine patients to be genetically positive for micrometastases. Three patients were both genetically and histologically negative. These three patients showed a significantly longer overall survival (P = 0.011) of 4, 5, and 20 years, respectively. CONCLUSIONS: We conclude that the genetic detection of micrometastases by MASA could be a powerful prognostic indicator for selecting patients with colorectal liver metastases who could benefit from liver transplantation.     

非小细胞肺癌淋巴结微转移的临床病理研究

目的 探讨免疫组化染色检测非小细胞肺癌淋巴结微转移的可行性。方法 将25例肺癌患者术中获取的淋巴结标本进行石蜡包埋,然后连续切片,6～10张不等,切片厚为5μm。选择第1和倒数第2张切片进行苏木精伊红染色,剩余切片用于免疫组化染色。免疫组化所选抗体为鼠抗人细胞角蛋白19单克隆抗体。结果 195枚淋巴结接受了苏木精伊红染色检查。9例患者共30枚淋巴结中发现有显性转移,无一例患者的淋巴结中检测出微转移。135枚苏木精伊红染色阴性的淋巴结又进行了免疫组化染色检查,有31枚淋巴结病理切片中显现出了癌微转移。16例常规病理PN0期患者中,5例患者肺门淋巴结出现了微转移;另9例常规病理PN1期患者中,4例出现了纵隔淋巴结的微转移,差异有统计学意义（x^2=52．900,P=0．0193）。结论 普通苏木精伊红染色能准确地检测出非小细胞肺癌淋巴结中的显性转移灶,而不易发现隐匿性微转移灶。免疫组化染色能提高非小细胞肺癌淋巴结微转移的检出率,并可对部分Ⅰ、Ⅱ期患者重新进行TNN分期。     

Re-evaluation of Axillary Skip Metastases in the Era of Sentinel Lymph Node Biopsy in Breast Cancer

Purpose To investigate whether skip axillary metastases are really skip metastases or a continuation of level I micrometastases in invasive breast cancer, and to determine whether there are any factors predisposing to skip metastases. Methods We reviewed 568 consecutive patients with breast cancer who underwent complete axillary lymph node dissections (ALND) between January 1998 and December 2004. For patients with skip axillary lymph node metastases, resectioning and immunohistochemical staining of the remaining part of paraffin blocks from level I lymph nodes were done to determine whether there were any micrometastases in this group of lymph nodes. Results Skip axillary metastases were found in 27 (10%) of 268 patients with axillary lymph node metastases. Re-evaluation of the level I lymph nodes, both with thin sectioning and immunohistochemical staining, in the patients with axillary skip metastases revealed no micrometastases. No significant correlation was found between the demographic and histopathological variables of the patients with skip metastases and those with regular axillary metastases. Conclusions These results suggest that skip axillary metastases are actual skip metastases, not a continuation of undetected level I micrometastases. Moreover, none of the clinical and histopathological measures of primary tumors are predictors of the presence of skip metastases.     

Do bone marrow micrometastases correlate with sentinel lymph node metastases in breast cancer patients?

BACKGROUND: Sentinel lymph node biopsies (SLNB) are used to detect axillary metastases as an important prognostic indicator for breast cancer patients. Bone marrow micrometastases (BMM) have also been shown to predict prognosis. This study examines whether SLNB and BMM are associated. STUDY DESIGN: A retrospective analysis was performed on 124 stages I to III breast cancer patients treated with mastectomy or lumpectomy, SLNB, and bone marrow aspiration between 1997 and 2003. SLNB were examined for the presence of metastases by hematoxylin and eosin (H&E) stains and also by immunohistochemistry (IHC) for lymph nodes negative by H&E. The kappa statistic was used to evaluate the association (agreement) between SLNB and BMM. RESULTS: In this study population, 36 patients (29%) had micrometastases detected in their bone marrow, and 51 patients (41%) had positive sentinel lymph nodes. Of the patients with positive BMM (n = 36), 53% (19 of 36) had positive SLNB (14 of 19 by H&E and 5 of 19 by IHC). In patients with negative BMM (n = 88), 36% (32 of 88) had a positive SLNB (27 of 32 by H&E and 5 of 32 by IHC). The kappa statistic and associated 95% confidence interval indicated poor agreement between SLNB and BMM (kappa = 0.15; 95% CI = -0.03, 0.32). CONCLUSIONS: There was poor agreement between axillary metastases and micrometastases detected in the bone marrow. This study suggests that BMM and axillary metastases are not concordant findings in most patients.