Incidence Of Lymph Node Micrometastases Research Articles

Prognostic significance of immunohistochemically detected lymph node micrometastases in pT0N0 esophageal squamous cell carcinoma

Pathological complete response (pCR) after chemoradiotherapy (CRT) is the best predictor of survival in patients with squamous cell carcinoma (SCC) of the esophagus. Although no adjuvant treatment is recommended for individuals who achieve pCR, approximately 30% of these patients develop a recurrence. We applied an immunohistochemistry (IHC) stain on resected lymph nodes to evaluate the incidence of lymph node micrometastases (LNMs) and its prognostic significance. Between 1995 and 2004, paraffin-embedded specimens for evaluating the presence of LNM were available for 52 pCR patients. We performed IHC staining with the cytokeratin antibody AE1/AE3 on resected lymph nodes and correlated the pathological findings to cancer recurrence and survival. A total of 510 lymph nodes from 52 patients were examined. The incidence of LNM in pathological complete responders after CRT was 11.5%. Only six patients were found to have AE1/AE3-positive cells in the IHC staining. However, patients with LNM had a higher recurrence rate (50% vs. 22%, P = 0.16) and a reduced disease-free survival rate (44% vs. 75%, P = 0.16). Patients with LNM had a 3.6-fold higher probability to develop recurrence compared with those without LNM (P = 0.15). LNMs are uncommon in pathological complete responders but hold prognostic significance.

Cytokeratin Is a Superior Marker for Detection of Micrometastatic Biliary Tract Carcinoma

The incidence of lymph node micrometastases in patients with biliary tract carcinoma is unknown. We evaluated the utility of three antibodies for immunohistochemical (IHC) detection of micrometastatic disease in patients with gallbladder and bile duct carcinoma. Surgical specimens from 35 patients with biliary tract carcinoma were evaluated. Histologically involved tissues were stained with the following antibodies using standard IHC techniques: cytokeratin (AE1:AE3), CEA (carcinoembryonic antigen), and EMA (epithelial membrane antigen). The antibodies with the greatest degree of positive staining were then used to evaluate the lymph nodes of patients with histologically negative lymph nodes. Micrometastatic disease was defined as clustered atypical cells <2 mm in size detected only with the use of IHC. All of the primary tumors and histologically positive lymph nodes demonstrated staining with cytokeratin and CEA antibodies, whereas only 83% were positive for EMA. Therefore, cytokeratin and CEA antibodies were used to evaluate histologically negative lymph nodes. Anti-cytokeratin immunostaining detected micrometastatic disease in two patients. Staining with anti-CEA was negative in all specimens. Overall, two of 15 patients with histologically node negative biliary tract carcinoma had occult micrometastases. Cytokeratin immunostaining enables detection of micrometastases in histologically negative lymph nodes in patients with biliary tract carcinoma. Prospective protocols incorporating cytokeratin staining of the lymph nodes may help determine the incidence and clinical significance of occult micrometastatic disease in these patients.

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

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

Immunohistochemical Assay for Lymph-Node Micrometastasis in Gastric Cancer and Correlation with Survival Rate

Purpose: The purpose of this study is to identify immunohistochemical evidence of lymph-node micrometastasis in histologic node-negative gastric cancer patients and to evaluate the prognostic significance of lymph-node micrometastasis.Materials and Methods: A retrospective study of 50 gastric cancer patients who underwent curative resections from October 1990 to November 1994 was performed. Two consecutive sections were prepared: one for ordinary hematoxylin and eosin staining, and the other for immunohistochemical staining with Pan cytokeratin antibody (Novocastra, UK). In the univariate analysis, the survival rate was calculated using the Life Table Method, and the multivariate analysis was determined using a Cox Proportional HazardsModel. The statistical analyses of the relationships between the clinicopathologic factors and micrometastases were performed by using a Chi-square test. Results: Of 2522 harvested lymph nodes, 81 () nodes and 19 () of 50 patients were identified as having lymphnode micrometastases by using immunohistochemical staining for cytokeratin. The incidence of lymph-node micrometastases was significantly higher in diffuse type carcinomas (, P=0.024) and in patients with serosal invasion (, P=0.05). For patients with lymph-node micrometastases (n=19), the 5-year survival rate was significantly decreased (, P=0.015). The Lauren's classirication (P=0.021) and the depth of invasion (P=0.035) were shown by multivariate analysis to have a significant relationship with the presence of micrometastases. Multivariate analysis revealed that lymph-node micrometastasis was independently correlated with survival in histologic node-negative gastic cancer patients. Conclusion: The presence of cytokeratin detected lymphnode micrometastases correlates with the worse prognosis for patients with histologic node-negative gastric cancer.

The incidence of lymph node micrometastases in patients pathologically staged N0 in cancer of oral cavity and oropharynx.

The presence of nodal metastasis in head and neck cancer is an important prognostic factor and crucial in making critical decisions regarding postoperative radiation treatment and follow up. The final documentation of nodal metastasis is still based on routine histopathological evaluation of the lymph nodes in the neck. The newer technologies including immunohistochemistry, molecular analysis and subserial sectioning may increase the detection of lymph node micrometastases in patients pathologically staged N0 in cancer of oral cavity and oropharynx.

Sentinel lymph node biopsy: is it indicated in patients with high-risk ductal carcinoma-in-situ and ductal carcinoma-in-situ with microinvasion?

Axillary lymph node status is the strongest prognostic indicator of survival for women with breast cancer. The purpose of this study was to determine the incidence of sentinel node metastases in patients with high-risk ductal carcinoma-in-situ (DCIS) and DCIS with microinvasion (DCISM). From November 1997 to November 1999, all patients who underwent sentinel node biopsy for high-risk DCIS (n = 76) or DCISM (n = 31) were enrolled prospectively in our database. Patients with DCIS were considered high risk and were selected for sentinel lymph node biopsy if there was concern that an invasive component would be identified in the specimen obtained during the definitive surgery. Patients underwent intraoperative mapping that used both blue dye and radionuclide. Excised sentinel nodes were serially sectioned and were examined by hematoxylin and eosin and by immunohistochemistry. Of 76 patients with high-risk DCIS, 9 (12%) had positive sentinel nodes; 7 of 9 patients were positive for micrometastases only. Of 31 patients with DCISM, 3 (10%) had positive sentinel nodes. 2 of 3 were positive for micrometastases only. Six of nine patients with DCIS and three of three with DCISM and positive sentinel nodes had completion axillary dissection; one patient with DCIS had an additional positive node detected by conventional histological analysis. This study documents a high incidence of lymph node micrometastases as detected by sentinel node biopsy in patients with high-risk DCIS and DCISM. Although the biological significance of breast cancer micrometastases remains unclear at this time, these findings suggest that sentinel node biopsy should be considered in patients with high-risk DCIS and DCISM.

Detection and significance of lymph node micro-metastases in patients with node-negative gastric carcinoma

Objective: To study micrometastases in lymph nodes from patients with node-negative gastric carcinoma by routine histologic examination and discuss their prognostic significance and the relationship between micrometastases and each of the clinicopathologic factors. Methods: A total of 1245 perigastric lymph nodes from 105 patients with node-negative gastric carcinoma was immunohisto-chemically detected using a monoclonal antibody against low molecular weight cytokeratin AE1. The characteristics of the micrometastases, their related factors and effect on patients’ survival after surgery were analysed and tested with statistical methods. Results: Micrometastases were observed in 81 lymph nodes (6.5%) of 31 patients (29.5%). The incidence of lymph node micrometastases was significantly higher in the diffuse type (41.5%) than in the intestinal type gastric carcinoma (17.6%,P<0.01,x 2test). In addition, the presence of micrometastases was closely correlated with the size and invasion depth of the primary tumor, but had no relation to patient’s age, sex and the location of primary tumor. The patients with micrometastases had significantly worse prognosis shown by Log-rank test. Their five-year survival rate after surgery was 61.29%; for those without micrometastases the rate was 82.43%,P=0.0116. When the number of patient’s lymph nodes with micrometastases was three or more, the five-year survival rate of these patients was much lower (41.67%,P=0.0012). Conclusion: The detection of lymph node micrometastases is necessary to more accurately determine the prognosis and clinical staging of patients with node-negative gastric carcinoma by routine histologic examination. The presence of micrometastases may be regarded as one of the clues in adjuvant therapy of those patients.