Significance Of Lymph Node Micrometastasis Research Articles

Abstract 3466: Prognostic implications of lymph node micrometastasis in patients with gastric cancer

Abstract Purpose: The clinical significance of lymph node micrometastasis (LNMM) remains controversial in gastric cancer (GC). In this study, we investigated the prognostic impact of patients with LNMM GC.Methods: A total of 624 patients with pathologically lymph node metastasis negative (pN0) and N1 status (pN1) who underwent gastrectomy between 2004 and 2018 were enrolled in this retrospective study. The diameter of tumor cell clusters in metastatic lymph nodes was measured in 120 patients with pN1 GC. Results: Patients with lymph node tumors of diameter < 1500 μm (LNMM) had significantly better prognosis than those with tumors of diameter ≥ 1500 μm (p = 0.012; log-rank test). Cox’s proportional hazards model revealed that LNMM (p = 0.016), several dissected lymph nodes (p = 0.049), and the provision of adjuvant chemotherapy (p = 0.002) were independent prognostic factors for overall survival of patients with pN1 GC. There was no significant difference in overall survival between patients with LNMM who received chemotherapy and those who did not (p = 0.332). Conclusions: LNMM is associated with favorable prognosis and could be an independent prognostic marker in patients with pN1 GC. LNMM in GC may be considered as one of the factors preventing adjuvant chemotherapy. Citation Format: Atsushi Yamamoto, Hirotaka Okamoto. Prognostic implications of lymph node micrometastasis in patients with gastric cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3466.

Prognostic impact of lymph node micrometastasis in patients with gastric cancer.

The clinical significance of lymph node micrometastasis (LNMM) remains controversial in gastric cancer (GC). In this study, we investigated the prognostic impact of LNMM in patients with GC. A total of 624 patients with pathologically lymph node metastasis-negative (pN0) and N1 status (pN1) who underwent gastrectomy between 2004 and 2018 were enrolled in this retrospective study. The diameter of tumor cell clusters in metastatic lymph nodes was measured in 120 patients with pN1 GC. Patients with lymph node tumors < 1500μm in diameter (LNMM) had a significantly better prognosis than those with tumors ≥ 1500μm in diameter (p = 0.012; log-rank test). Cox's proportional hazards model revealed that LNMM (p = 0.016), several dissected lymph nodes (p = 0.049), and the provision of adjuvant chemotherapy (p = 0.002) were independent prognostic factors for the overall survival of patients with pN1 GC. There was no significant difference in the overall survival between patients with LNMM who received chemotherapy and those who did not (p = 0.332). LNMM is associated with a favorable prognosis and maybe an independent prognostic marker in patients with pN1 GC. LNMM in GC may be considered a factor preventing adjuvant chemotherapy.

Clinical significance of lymph node micrometastasis in T1N0 early gastric cancer.

To investigate the significance of lymph node micrometastasis in T1N0 early gastric cancer. Lymph node micrometastasis may be a key mechanism in the recurrent T1N0 EGC patients after surgical treatment. It's unknow whether it is safe to leave the lymph nodes with micrometastasis untreated after ESD. A total of 106 T1N0 EGC patients were enrolled in this study. Immunohistochemical technique with CAM5.2 was employed to detect lymph node micrometastasis, and Immunohistochemical with D2-40 was used to detect the lymphatic vessels. Prognostic significance of lymph node micrometastasis and the relationship of lymph nodes micrometastasis with Clinicopathological features were analyzed. Twenty-two of the 106 T1N0 EGC cases were detected with lymph nodes micrometastasis, with the detection rate of 20.8%. The median survival time of the group with positive lymph nodes micrometastasis was lower than that of the group with negative micrometastasis, 48 vs 60 months. The incidence of lymph nodes micrometastasis in submucosal T1N0 EGC was 23.9%, while no micrometastasis was found in the mucosal T1N0 EGC. Of all the 30 cases according with the expanded ESD indications, six patients were found with lymph nodes micrometastasis. The occurrence of lymph node micrometastasis was common in T1N0 EGC. The cases with positive lymph nodes micrometastasis showed a lower median survival time than those with negative micrometastasis. lymph nodes micrometastasis incidence was higher in the submucosal ECG than in the mucosal ECG. lymph nodes micrometastasis was also found in the cases according to the expanded ESD indications.

Lymph Node Micrometastasis Prognosticates Survival for Patients with Stage 1 Bronchogenic Adenocarcinoma

This study aimed to investigate the significance of lymph node micrometastasis (LNMM) in the lung cancer nodal categories. Between 1 January 2009 and 31 December 2013, 589 patients with suspected c-stage 1 and p-T1-2aN0-1M0 lung adenocarcinoma were enrolled in this study. The study evaluated LNMM with cytokeratin (AE1/AE3) and transcription factor-1 (TTF1) (8G7G3/1) expression by immunohistochemistry. Recurrence-free survival (RFS) and overall survival (OS) were compared among the T1-2aN0-1M0 patients stratified by the new N categories. From 589 patients, 7892 removed lymph nodes were examined, and LNMM was observed in 55 (9.3%) of the patients. The patients without LNMM or N1 had the best RFS (5-year rate: 80% vs 25%; P < 0.001) and OS (5-year rate: 87% vs 43%; P < 0.001), followed by the patients with LNMM, compared with those in the N1 category (RFS: 5-year rate, 25% vs 8%; P = 0.010; OS: 5-year rate, 43% vs 20%; P = 0.009). Similarly, this trend was observed when patients were subdivided into the T1 and T2a categories. Multivariate analysis showed that the new N categories with the addition of LNMM were an independent prognostic factor. This result also was noticed in all subgroups. The findings showed LNMM to be clinically significant as a risk factor for lung cancer. Clinicians should consider LNMM when estimating N categories to determine prognosis and the best treatment strategy.

Long-term breast cancer survival in relation to the metastatic tumor burden in axillary lymph nodes.

The clinical significance of lymph node micrometastases and isolated tumor cells (ITCs) in breast cancer is still controversial. After a median follow-up of 52 months, a report from the Swedish Multicenter Cohort Study presented a worse cancer-specific and event-free survival for patients with micrometastases than node-negative individuals, but could not demonstrate a significant difference in overall survival (OS). Due to the tendency of breast cancer to relapse after more than 5-10 years, we now report the long-term survival of the cohort. Between September 2000 and January 2004, 3355 breast cancer patients were included in a prospective cohort. Sentinel lymph node biopsy was always performed. Patients were classified in four groups according to their overall nodal stage: node negative (N0, 2372), ITCs (113), micrometastases (123), and macrometastases (747). Kaplan-Meier survival estimates and Cox proportional hazard regression models were applied. Median follow-up was 156months. Ten-year cancer-specific survival and OS were significantly lower in case of micrometastases than in N0 (84.7 vs. 93.5%, p = 0.001, and 75.5 vs. 84.2%, p = 0.046, respectively). In case of macrometastases, corresponding survival rates were 82.8 and 74.3%. Only for those aged less than 50 years, cancer-specific survival and OS were significantly worse in case of ITCs than N0. Patients with micrometastases received less often chemotherapy than those with macrometastases (24.4 vs. 53.9%). Lymph node micrometastases in breast cancer have a prognostic significance. This study demonstrates a similar survival for patients with micrometastases and those with macrometastases, possibly due to systemic undertreatment.

Novel surgical approach based on the sentinel node concept in patients with early gastric cancer.

Recent prospective multicenter trials have demonstrated the clinical safety and efficacy of sentinel node navigation surgery (SNNS) in patients with early gastric cancer. Further, development of an intraoperative imaging system and an indocyanine green fluorescence imaging approach has been attracting attention as a novel tool for detection of the sentinel node (SN). The greatest advantage of an in vivo imaging system is that it visualizes SN and afferent lymphatic vessels from the primary tumor site more clearly than the conventional dye approach. Besides visualization of the SN, it is also essential to accurately assess the presence or absence of lymph node metastasis in the intraoperative management of SNNS. However, the clinical significance of lymph node micrometastasis (LNM) in patients with gastric cancer remains controversial. Reverse transcription‐polymerase chain reaction (RT‐PCR) is one of the representative assays used to identify LNM. A rapid RT‐PCR assay that completes the detection of LNM within approximately 40 minutes has recently been produced and applied in the clinical management of SNNS. From the viewpoint of surgical methods, modified laparoscopic and endoscopic cooperative surgery with non‐exposed approaches has recently been highlighted as a promising technique to prevent tumor dissemination caused by surgical procedures, and is likely to be clinically applied to SNNS in the future. When carrying out SNNS as a minimally invasive surgery, it is important to consider the balance between post‐surgical quality of life and curability. Future prospective studies on SNNS will greatly contribute to furthering its establishment as a beneficial procedure for patients with early gastric cancer.

Lymph node micrometastasis in gallbladder cancer.

Prognosis of gallbladder cancer (GBC) is grim even after curative surgery. Lymph node metastasis is the most important prognostic factor, but distant relapses occurring in their absence point towards additional factor. Lymph node micrometastasis could be one. The present study aimed to evaluate the incidence and clinical significance of lymph node micrometastasis. This is a prospective study of patients undergoing curative surgery for GBC from 1 March 2013 to 30 April 2015, at our institute. All lymph nodes were examined with hematoxylin and eosin and immunohistochemistry against CK7. The incidence of lymph node and its relation to other clinicopathological parameters, recurrence, and survival was evaluated. Out of 589 lymph nodes retrieved from 40 patients, metastasis was seen in 13 (2.20%) nodes from 8 (20%) patients and micrometastasis in 4 (0.68%) nodes from 3 (7.5%) patients. Micrometastases were absent in pT1 tumors (0/10 in pT1 vs. 3/30 in pT2-4) and more common in patients with nodal metastasis (13% vs. 6%). Though the presence of micrometastasis would have upstaged the disease, it did not statistically relate to clinicopathological parameters, recurrence, and survival. Incidence of lymph node micrometastasis in GBC was low and did not correlate with other clinicopathological parameters, recurrence, and survival.

Impact of lymph node micrometastasis on gastric carcinoma prognosis: a meta-analysis.

To investigate the prognostic significance of lymph node micrometastasis (LNMM) in patients with gastric carcinoma. Two reviewers independently searched electronic databases including PubMed, EMBASE, the Cochrane Database of Systematic Reviews, the Cochrane Controlled Studies Register, and the China National Knowledge Infrastructure electronic database between January 1996 and January 2014. Strict literature retrieval and data extraction were performed to extract relevant data. Data analysis was conducted using RevMan 5.2.4 software, and relative risks (RRs) for patient death in five years and recurrence were calculated. A fixed- or random-effects model was selected to pool and a forest plot was used to display RRs. Twelve cohort studies containing a total of 1684 patients were identified. LNMM positivity was worse than LNMM negativity with regards to the number of patients who died in five years. The effects of LNMM positivity in patients with gastric cancer of different T-stages remain unclear. LNMM in patients with gastric carcinoma was also associated with a higher recurrence rate. With regards to the number of patients who died in five years, Asian patients were worse than European and Australian patients. We recommend that LNMM should not be used as a gold standard for prognosis evaluation in patients with gastric cancer in clinical settings until more high quality trials are available.

Should lymph node micrometastasis be considered in node staging for gastric cancer?: the significance of lymph node micrometastasis in gastric cancer.

In TNM staging system, lymph node staging is based on the number of metastatic lymph nodes in gastric cancer and micrometastasis is not considered. Several reports proposed the importance of lymph node micrometastasis as the causative factor for recurrence and poor survival, but it remains controversial among researchers. A total of 482 gastric cancer patients who underwent curative resection from 2004 to 2010 at Korea University Medical Center Ansan Hospital, South Korea were prospectively enrolled. For detecting lymph node micrometastasis, immunohistochemical staining with anti-cytokeratin antibody (CAM 5.2) was performed on negative lymph nodes by hematoxylin-eosin (H-E) staining. Survival differences were compared between conventional node staging and new node staging that took micrometastasis into consideration. Also, the prognostic value of lymph node micrometastasis was investigated in multivariate analysis. A total of 156 patients (32.4%) showed lymph node micrometastasis. Overall, the micrometastatic group had more advanced tumor and lymph node stage, lymphovascular cancer cell invasion, a higher rate of recurrence, and poor survival. Furthermore, when the cumulative numbers of macro- and micrometastatic lymph nodes were calculated together, the discriminative power of survival difference between each node stage became more stratified. Also, multivariate analysis using Cox's proportional hazards model demonstrated perineural invasion, pathologic T stage, dissected lymph nodes, macro- and micrometastatic lymph nodes are independent prognostic factors. Lymph node micrometastasis was clinically significant as a risk factor for recurrent gastric cancer. Lymph node micrometastasis should be considered when estimating TNM stage for determining prognosis and the best treatment strategy.

Assessment of Sentinel Node Concept in Esophageal Cancer Based on Lymph Node Micrometastasis

The clinical significance of lymph node micrometastasis remains unclear in patients with esophageal cancer. Therefore, accurate assessment of lymph node status including micrometastasis is important when performing sentinel node (SN) navigation surgery. The purpose of the present study was to investigate the adequacy of SN concept based on lymph node micrometastasis determined by immunohistochemistry (IHC) and reverse transcription-polymerase chain reaction (RT-PCR) in patients with esophageal cancer. A total of 57 patients with esophageal cancer who were preoperatively diagnosed as having T1-T2 (cT1-T2) and N0 (cN0) were enrolled. They underwent standard esophagectomy with lymph node dissection. One day before surgery, a total of 3 mCi of 99mTechnetium-tin colloid was endoscopically injected into the submucosa around the tumor. During the operation, radioisotope uptake in the lymph nodes was measured using Navigator GPS. All dissected lymph nodes were investigated by RT-PCR using the double marker of CEA and SCC, hematoxylin-eosin (HE) staining, and IHC. Node-positive incidence identified by HE and IHC was 12.3% (7/57) and 19.3% (11/57), respectively. RT-PCR demonstrated micrometastasis in four of 46 patients without nodal metastasis determined by HE staining and IHC. No non-SN metastases were found in 42 patients without micrometastasis identified by IHC and RT-PCR of SN. Accuracy and false negative rates were 100% (57/57) and 0% (0/42), respectively. SN concept might be acceptable in patients with cT1-T2 and cN0 esophageal cancer, even in the presence of micrometastasis identified by IHC and RT-PCR.

Molecular diagnosis and prognostic significance of lymph node micrometastasis in patients with histologically node-negative non-small cell lung cancer

Lymph node metastasis is a major prognostic factor in resected non-small cell lung cancer (NSCLC). However, 30-40 % rate of recurrence after performing complete resection in node-negative patients suggests that their nodal staging is suboptimal. We aimed to evaluate the molecular diagnosis and prognostic significance of lymph node micrometastasis in patients with node-negative NSCLC. Primary tumor samples from 62 patients with resected stage I-IIB NSCLC were screened for fragile histidine triad (FHIT) and CDKN2A mRNA deletion using reverse transcriptase polymerase chain reaction (RT-PCR). The molecular alternations were found in tumors of 49 patients. A total of 269 lymph nodes from these 49 NSCLC patients with FHIT or/and CDKN2A deletion tumors were examined. Fifteen positive-control nodes and ten negative-control nodes were also analyzed for FHIT and CDKN2A mRNA deletion. Thirty-nine (22 %) and 22 (18 %) lymph nodes from the 49 patients with FHIT and CDKN2A mRNA deletion in primary tumor had FHIT and CDKN2A mRNA deletion, respectively. The types of FHIT and CDKN2A mRNA deletion in lymph nodes were identical with those in their primary tumors. By combination of two markers, 16 patients (32.7 %) were found to have nodal micrometastasis. Survival analysis showed that patients with nodal micrometastasis had reduced disease-free survival (P = 0.001) and overall survival (P = 0.002) rates. Multivariate analysis demonstrated that nodal micrometastasis was an independent predictor for worse prognosis. Thus, the detection of lymph node micrometastasis by FHIT and CDKN2A mRNA deletion RT-PCR will be helpful to predict the recurrence and prognosis of patients with completely resected stage I-IIB NSCLC.

Clinical significance of lymph node micrometastases in cervical cancer

In most cancers of epithelial origin, metastases to the lymph nodes constitute the most important prognostic factor and are predictive of the results of the surgical and adjuvant therapies. Data on the lymph node status allows to design an appropriate treatment plan. Despite advances in gynecologic oncology the importance of lymph node micrometastases in cervical cancer especially in nonsentinel lymph nodes which are detected by ultrastaging, has not been fully elucidated. The purpose of the article is to familiarize the reader with the state of current knowledge on cervical cancer micrometastases. The authors attempt to answer the question about the benefits of lymph node assessment in the search for micrometastases in cervical cancer as well as to address emerging doubts.

The incidence and clinical significance of lymph node micrometastases determined by immunohistochemical staining in stage I - lymph node negative endometrial cancer.

Determine the incidence and clinical relevance of lymph node micrometastases found with immunohistochemical (IHC) staining in patients diagnosed with stage I lymph node-negative endometrial adenocarcinoma. Eligible patients with endometrioid-type histology and negative lymph nodes by H&E were identified by a computerized database. After histologic confirmation, all paraffin-embedded pathologic specimens were freshly sliced and stained with IHC stains for pancytokeratin. Slides were interpreted by two pathologists and positive IHC staining for micrometastases was defined as positive staining of cells <2 mm in greatest dimension. Patient demographics, clinicopathologic factors, and follow-up data were abstracted. Fifty-one patients were included in our study. Most patients had stage IA (84%) tumors of grade 2/3 histology (51%), and 11 patients (22%) received adjuvant therapy. Mean number of lymph nodes was 12.2 per patient. Of 151 lymph node paraffin blocks evaluated for pancytokeratin, only two (1.3%) had IHC-positive micrometastases. The two lymph node-positive results occurred in separate patients, leading to 3.9% of all patients in our cohort. Both micrometastatic lymph node-positive patients had adjuvant radiation therapy for uterine high-risk factors and are currently without evidence of disease at 15 and 16 months, respectively. Three lymph node-negative patients (6.1%) have developed recurrences within a median follow-up of 15 months. The incidence of IHC stain-positive micrometastases in H&E-negative lymph nodes is low in surgically staged endometrial cancer and does not justify routine IHC staining. Additionally, as little evidence exists to support the clinical significance of IHC-stained micrometastases in endometrial cancer, further study is warranted.

Significance of Lymph Node Micrometastasis in Pancreatic Cancer Patients

Background /Aims: The present study deals with the significance of lymph node micrometastasis in the survival rate for pancreatic cancer patients. Methods: Between January 2006 and December 2010 at the First Department of Surgery in Košice, a prospective trial was done in which we investigated the survival rate after radical pancreatic resection. All negative lymph nodes removed during standard radical lymphadenectomy were subjected to immunohistochemical staining to detect occult micrometastasis. A comparison of the median survival rate in groups of patients with immunohistochemistry-positive and -negative lymph nodes was performed. Results: Radical pancreatic resection with standard radical lymphadenectomy was performed on 64 pancreatic cancer patients. The median survival time was 15 months. Out of the 319 histopathologically negative lymph nodes (34 patients), 134 lymph nodes were classified as immunohistochemistry positive (21 patients). The median survival rate in the group of patients with immunohistochemistry-negative lymph nodes was 23 months, but in the group of patients with immunohistochemistry-positive lymph nodes it was 14 months. There was a statistically significant difference between these 2 groups of patients (p ≤ 0.01). Conclusion: The immunohistochemical examination of histopathologically negative lymph nodes can lead to positive lymph node detection. The presence of lymph node micrometastasis could predict the survival rate.

Adverse prognosis of clustered‐cell versus single‐cell micrometastases in pN0 early gastric cancer

The clinical significance of lymph node micrometastasis (MM) for pN0 early gastric cancer is not well documented. The aim of this study is to clarify the risk factors of lymph node MM and the prognostic significance of the type of lymph node MM in patients with pN0 early gastric cancer. We investigated the lymph node MM with using an anticytokeratin immunohistochemical stain in 160 patients with pN0 early gastric cancer who underwent curative resection between 2000 and 2005. We identified lymph node MM in 34 of 160 patients (21.3%), and in 84 of 1,656 lymph nodes (5.1%). MM occurred as single-cell type in 10 patients and as cell cluster type in 24 patients. MM was significantly associated with tumor size (P = 0.041) and lymphatic invasion (P = 0.008). The statistically significant prognostic factors affecting 5-year survival rates were depth of tumor invasion (P = 0.020), tumor size (P = 0.035), lymphatic invasion (P = 0.018), MM (P < 0.001), and type of MM (P < 0.001). Cox regression survival analysis revealed that the presence of MM, and particularly the cluster-type MM (P < 0.001), were independent prognostic factors in pN0 early gastric cancer patients. The incidence of lymph node MM in patients with node negative early gastric cancer was 21.3%, and cancer cell cluster type of MM proved a primary independent prognostic factor for pN0 early gastric cancer patients.

The E-Cadherin expression and its clinical significance of lymph node micrometastases in colorectal carcinoma

Objective Purpose To detect the expression of E-cadherin in colorectal carcinoma and lymph node micrometastases,and investigate their relationship.Methods 82 cases of lymph node simple was dectected with RT-PCR method using CK20 mRNA acridinium ester.in screening colorectal carcinoma lymph node micrometastases.E-Cadherin expression analysed by immuno-histochemical staining(the SP method) in colorectal cancer tissue,tissue nearby cancer,the normal control tissue.Results In 60 cases of colorectal carcinoma,the expression of E-Cadherin was 71.67%.Number of positive nodes was 55.8%,the expression of E-cadherin was 56.7%(34 cases) and number of positive nodes was 45.5%(356 cases) through routine pathological examination.The low level expression of E-Cadherin was positively correlated with the Dukes staging,serosa infiltration,lymph node and liver metastasis of colorectal carcinoma(x2 = 16.72,P ＜ 0.05).The expression of E-Cadherin was negative in 6 of the 11 patients with lymph node micrometastases,and in 6.67% 1 of the 15 patients without lymph node micrometastases(x2 = 4.160,P = 0.041).Conclusion The negative expression of E-Cadherin may contribute to lymph node micrometastases in colorectal carcinoma. Key words: colorectal carcinoma; E-Cadherin; Lymphatic metastasis; Rt-pcr

Breast Cancer Survival in Relation to the Metastatic Tumor Burden in Axillary Lymph Nodes

The aim of this study was to determine the prognostic significance of lymph node micrometastases in patients with breast cancer. Between September 2000 and January 2004, 3,369 patients with breast cancer were included in a prospective cohort. According to their lymph node status, they were classified in the following four groups: 2,383 were node negative, 107 had isolated tumor cells, 123 had micrometastases, and 756 had macrometastases. Median follow-up time was 52 months. Kaplan-Meier estimates and the multivariate Cox proportional hazard regression model were used to analyze survival. Five-year cause-specific and event-free survival rates were lower for patients with micrometastases (pN1mi) than for node-negative (pN0) patients (94.1% v 96.9% and 79.6% v 87.1%, respectively; P = .020 and P = .032, respectively). There was no significant survival difference between node-negative patients and those with isolated tumor cells. The overall survival of pN1mi and pN0 patients did not differ. This study demonstrates a worse prognosis for patients with micrometastases than for node-negative patients.

Analysis of micrometastatic disease in histologically negative lymph nodes of patients with adenocarcinoma of the distal esophagus or gastric cardia

Lymphatic dissemination is the most important prognostic factor in patients with esophageal carcinoma. However, the clinical significance of lymph node micrometastases is still debated due to contradictory results. The aim of the present study was to identify the incidence of potentially relevant micrometastatic disease in patients with histologically node-negative esophageal adenocarcinoma and to analyze the sensitivity and specificity of three different immunohistochemical assays. From a consecutive series of 79 patients who underwent a transthoracic resection with extended 2-field lymphadenectomy, all 20 patients with pN0 esophageal adenocarcinoma were included in this study. A total of 578 lymph nodes were examined for the presence of micrometastases by immunohistochemical analysis with the antibodies Ber-EP4, AE1/AE3 and CAM 5.2. Lymph node micrometastases were detected in five of the 20 patients (25%). They were identified in 16 of the 578 lymph nodes examined (2.8%) and most frequently detected with the Ber-EP4 and AE1/AE3 antibody (sensitivity 95% and 79% respectively). In 114 of the 559 negative lymph nodes (20.4%), positive single cells were found that did not demonstrate malignant characteristics. These false-positive cells were more frequently found with the AE1/AE3 staining (specificity of the Ber-Ep4 and AE1/AE3 antibody 94% and 84% respectively). The presence of nodal micrometastases was associated with the development of locoregional recurrences (P=0.01), distant metastases (P=0.01), and a reduced overall survival (log rank test, P=0.009). For the detection of clinically relevant micrometastatic disease in patients operated upon for adenocarcinoma of the distal esophagus or gastric cardia, Ber-EP4 is the antibody of first choice because of its high sensitivity and specificity. Immunohistochemically detected micrometastases in histologically negative lymph nodes have potential prognostic significance and are associated with a high incidence of both locoregional and systemic recurrence. Therefore, this technique has the potential to refine the staging system for esophageal cancer and to help identify patients who will not be cured by surgery alone.

Lymph node micrometastasis in node negative early gastric cancer

Aims The clinical significance of lymph node micrometastasis for histologically node negative gastric cancer is not well documented. This study was to assess the incidence and to clarify the risk factors of lymph node micrometastasis in patients with node negative early gastric cancer (EGC). Methods We investigated the lymph node micrometastasis with using an anticytokeratin immunohistochemical stain in 90 patients with node negative EGC who underwent curative resection between 1991 and 2000. Results Among 3526 nodes from 90 patients, there were 17 cytokeratin immunohistochemical stain positive nodes from nine patients. The incidence of micrometastasis was higher in patients with lymphatic invasion ( p = 0.012), venous invasion ( p = 0.026) and larger tumor ( p = 0.003). The independent risk factors for lymph node micrometastasis were lymphatic invasion ( p = 0.004, RR = 22.915, 95% CI = 2.709 ∼ 193.828) and tumor size ( p = 0.029, RR = 1.493, 95% CI = 1.042 ∼ 2.138). Although there were 10 deaths during the follow-up period of mean 67.6 months (1 month ∼ 147 months), there was no death from a cancer recurrence. Conclusions The incidence of lymph node micrometastasis in patients with node negative early gastric cancer was 10%, and the independent risk factors for micrometastasis were lymphatic invasion and tumor size.

The clinical significance of lymph node micrometastasis in stage I and stage II colorectal cancer

Recent advances in immunohistochemical techniques have made it possible to identify micrometastasis using antibodies to cytokeratins (CK). The aim of the study was to determine the prevalence and prognostic significance of immunohistochemically detected micrometastasis (IHM) in patients with localised colorectal cancer (CRC) (Dukes' A and B). A further aim was to study the prognostic role of histopathological factors such as vascular invasion. The original histology of 168 consecutive patients with Dukes' A or B tumours who had undergone curative resection was reviewed. Immunohistochemical staining was performed using CK antibodies, AE1/AE3 and MNF116 on all (n=898) lymph nodes. Survival analysis was performed on 105 cases that had been followed up until death or for at least 5 years. IHM were detected in 17.3% of lymph nodes analysed. Adverse outcome (death/local recurrence) was recorded in 8/49 (16%) patients with IHD-positive nodes and in 10/56 (18%) patients negative for IHM. IHM was not associated with adverse outcome on either univariate (p=0.540) or multivariate analyses (p=0.673). There was no correlation of IHM with age, gender, site, size and grade of tumour, depth of tumour invasion or perineural and vascular invasion. Vascular invasion was the only independent prognostic factor identified. We have shown that isolated CK-positive epithelioid cells are commonly found in morphologically benign pericolic lymph nodes of patients with localised (Dukes' A or B) CRC. These cells may represent occult micrometastasis but are not clinically significant. Vascular invasion identifies patients with localised CRC likely to develop recurrences or die of disease.