Detection Of Lymph Node Micrometastases Research Articles

Detection of lymph node micrometastases in esophageal carcinoma: Pathology of lymph node involvement

Detection of lymph node micrometastases in esophageal carcinoma: Pathology of lymph node involvement

Distribution of lymph node metastasis including micrometastasis in early gastric cance

Background: Recently, various type of surgical treatment such as endoscopic mucosal resection, laparoscopic gastrectomy has been performed in early gastric cancer. When the indication of such treatments is decided, it is important to diagnose the lymph node metastasis as correct as possible. The development of sensitive immunohistochemical techniques relying on specific monoclonal antibodies has made possible the detection of lymph node micrometastasis. The purpose of this study was to analyze the distribution of lymph node metastasis including micrometastasis in early gastric cancer. Patients and methods: A total 324 patients with early gastric cancer were enrolled in this study between 1973 and 1998. Of these, 178 patients had mucosal cancer and 146 submucosal cancer. Lymph node metastasis was found in 32 patients by routine histological examination. Immunohistochemical examination using anti-cytokeratin antibody was performed in 57 patients with submucosal cancer between 1990 and 1998. The tumor location was divided into 7 regions, namely, upper and lesser curvature (UlLess), upper and great curvature (UlGre), middle lesser curvature (MlLess), middle greater curvature (MlGre), lower and lesser curvature (LlLess), lower and greater curvature (LlLess) and esophageal invasion (E). Results: Lymph node metastasis was found in 2% (2/178) of mucosal cancer and 20% (30/146) of submucosal cancer. Significant difference was found in tumor size and tumor depth between node positive and node negative patients. In patients with tumor at E and UlLess, MlLess and MlGre, lymph node metastasis was distributed along the left gastric artery. The patients with LlLess tumor had lymph node metastasis along left and right gastric artery, and right gastro-epiploic artery. In UGre tumor, lymph node metastasis was found in right gastro-epiploic artery. The incidence of micrometastasis was detected by immunohistochemistry was 9 of 47 in node negative patients and 7 of 10 in node positive patients by histology. The distribution of lymph node micrometastasis was similar to the area distributed as above. Conclusion: Lymph node metastasis in early gastric cancer was distributed according to the lymphatic pathway of tumor location. Since lymph node micrometastasis was found in even early gastric cancer, especially in submucosal cancer, histologic examination of lymph node during operation is recommended for minimally invasive surgery.

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.

Clinical usefulness of telomerase assay for the detection of lymph node metastasis in patients with oral malignancy.

Telomerase is considered a diagnostic marker of malignancy. We investigated the usefulness of telomerase assay for the detection of lymph node micrometastasis. Sixteen cervical lymph nodes with metastasis of oral cancer and 20 benign lymph nodes were studied. The oral cancer cell line was used to estimate the sensitivity for telomerase assay. Telomerase activity was measured by semiquantitative telomeric repeat amplification protocol. There was a significant difference between malignant and benign lymph nodes. The telomerase activity of 50 mg of lymph nodes with 103 or more cancer cells differed from that of control lymph nodes. Lymph nodes with 102 or fewer tumor cells expressed similar levels as benign lymph nodes. In addition to routine histologic examination, telomerase assay is considered a useful tool for the detection of lymph node metastasis in patients with oral malignancy.

Immunohistochemically detected micrometastases in peribronchial and mediastinal lymph nodes from patients with T1, N0, M0 pulmonary adenocarcinomas.

The T1, N0, M0 subset of stage I lung adenocarcinoma is a tumor that has a 5-year disease-free survival rate of 66% to 85%. To date, there has not been a rigorous immunohistochemically detected lymph node micrometastasis study composed of patients with identical stage and type of tumors, and in which standard histologic features were incorporated into multivariate analyses. We immunohistochemically examined the peribronchial and mediastinal lymph nodes from 80 consecutively accrued patients with T1, N0, M0 adenocarcinomas and bronchioloalveolar carcinomas unselected for distant metastasis, and an additional 39 patients with similar stage and type neoplasms who were selected for their development of metastases to evaluate the prevalence of micrometastases, their association with distant metastases, and their relationship with other pathologic prognostic features. All slides were stained with keratin AE1/3. Micrometastases were confirmed with Ber-Ep4. Three immunohistochemically detected lymph node micrometastases were identified in three of 80 consecutively accrued patients (4%). These three positive stains constituted 0.5% of the 573 stains required to immunohistochemically screen all of the lymph node blocks from these patients. Among the 39 patients who were selected because they developed distant metastases, three immunohistochemically detected lymph node micrometastases from three patients were identified, which constituted 8% of patients in this group and 1% of the 280 stains required to screen all of these patients' lymph nodes. Small vessel invasion, maximum tumor dimension, and immunohistochemically detected lymph node micrometastases were independently associated with metastases on multivariate analysis. Among patients who developed metastases, there was no significant difference in the disease-free survival rate between those with and those without immunohistochemically detected lymph node micrometastases. Given the low sensitivity in terms of the number of immunohistochemical stains performed, and the prognostic significance of standard histologic features, the use of immunohistochemical screening lymph nodes from all patients with T1, N0, M0 adenocarcinomas is questionable.

Is Extended Selective Supraomohyoid Neck Dissection Indicated for Treatment of Oral Cancer with Clinically Negative Neck?

Oral cavity tumors may develop occult metastases to the cervical lymph nodes. Current imaging techniques and routine histopathologic methods may fail to detect lymph node micrometastases, but the surgeon has to electively dissect a neck at risk of developing clinical disease. Supraomohyoid neck dissection has been the elective surgery for treating a clinically negative neck in patients with oral cavity primaries. A literature review revealed that level IV nodes can be significantly affected by occult disease with and without metastases in level I-III lymph nodes. This means that level IV nodes have to be included in the supraomohyoid neck dissection, resulting in a more extensive surgical procedure to ensure a margin of oncological safety.

Lymph node metastasis from ductal carcinoma in situ with microinvasion.

Widespread use of mammography has increased the detection of ductal carcinoma in situ with microinvasion (DCISM) in pathology specimens. Currently there is disagreement regarding the incidence of axillary metastasis from DCISM. The controversy centers on whether complete lymphadenectomy is indicated for axillary staging, given its morbidity and the reportedly minimal rate of axillary involvement in these patients. Intraoperative lymphatic mapping and sentinel lymphadenectomy (SLND) may obviate complete axillary lymph node dissection in selected breast carcinoma patients. In intraoperative lymphatic mapping, isosulfan blue dye is used to demonstrate the course of lymphatic flow from the breast tumor to the first draining or sentinel lymph node. This blue-stained lymph node is selectively excised for pathologic examination; its tumor status is used to predict the tumor status of the other axillary lymph nodes. The authors examined whether SLND would be suitable for staging DCISM. From February 1992 to January 1997, 14 patients with DCISM underwent intraoperative lymphatic mapping and SLND at the John Wayne Cancer Institute in Santa Monica, California. Clinical and pathologic data were prospectively collected. Primary DCISM tumors ranged in size from 0.9 to 6.5 cm. Nine patients presented with mammographic abnormalities, two patients presented with Paget's disease and a palpable lesion, and three patients presented with palpable lesions. Two patients (14.3%) had tumor-involved sentinel lymph nodes. One of these patients had two sentinel lymph nodes, both of which contained single cancer cells identified by immunohistochemistry. The other patient had 1 sentinel lymph node, in which a 0.3-cm metastasis was revealed by light microscopy. Completion axillary dissection was performed on both patients and revealed no further tumor positive lymph node metastases. SLND can detect lymph node micrometastases (tumor deposits <2 mm) in patients with DCISM. The clinical relevance of these micrometastases is unknown, but their existence shows that DCISM can involve the lymph nodes.

884 - Immunohlstochemlcally detected lymph node micrometastases (N1A-IHC) in breast cancer (BC)

884 - Immunohlstochemlcally detected lymph node micrometastases (N1A-IHC) in breast cancer (BC)

P53 immunohistochemical analysis of the lymph nodes in node-negative breast cancer patients who had subsequent relapse

We performed a genetic dignosis using p53 immunohistochemistry for the detection of lymph node micrometastasis. Immunohistochemical analysis was performed in 12 node-negative patients with breast cancer who subsequently showed relapse. There was no p53 immunostaining in 197 lymph nodes from 12 patients, while 2 were positive in the 12 primary lesions. p53 immunohistochemistry is not an alternative method for detecting lymph node micrometastasis in node-negative breast cancer.

Our Experience with the Enhanced Polymer One-step Staining in Frozen Sections

Rott T, Velkavrh D. Our experience with the enhanced polymer one-step staining in frozen sections. Acta Otolaryngol (Stockh) 1997; Suppl 527: 114-115.The enhanced polymer one-step staining (EPOS) method is presented with minor modifications for intraoperative frozen sections. It can be applied in almost every department of pathology where there is a necessity, because no special equipment is required. The method is rapid and immunostaining can be performed in less than 1.5 min. Antibodies are available for more than 20 important tissue and tumor markers. Out of those, antibodies against human cytokeratin, leukocyte common antigen (LCA) and chromogranin A were introduced in routine work. The first 2 antibodies yield excellent results and are a big advantage in routine diagnostic work: the use of cytokeratin is useful for confirmation or exclusion of suspected tumor invasion, especially in cases of atypical hyperplastic lesions, for detection of spindle cell carcinomas, and the detection of lymph node micrometastases. LCA demonstration is helpful in differentiating various round cell tumors, such as poorly differentiated carcinomas, sarcomas, malignant lymphomas, and evaluation of inflammatory response. Chromogranin A may detect neuroendocrine differentiation in the tumors.

The prognostic significance of immunohistochemically detected lymph node micrometastases in colorectal carcinoma.

Micrometastases have been detected by immunocytochemical means in the lymph nodes of patients with otherwise node-negative cancer of the colon and rectum. This study examines the incidence and prognostic significance of nodal micrometastases in Dukes' B carcinoma. Five hundred and fifty-nine lymph nodes from 77 cases of Dukes' B carcinoma were examined for lymph node micrometastases by immunocytochemical staining for cytokeratin AE1:AE3. Micrometastases were detected in 19 cases (25 per cent). Cell clusters were present in ten cases, the remaining nine cases displaying only single cells. The presence of micrometastases was unrelated to age (P = 0.06), sex (P = 0.32), tumour site (P = 0.37), tumour size (P = 0.67), or tumour differentiation (P = 0.66). Ten-year survival estimates by the Kaplan-Meier lifetable method was 47 per cent in patients with and without micrometastases (chi 2 = 0.35 and 1 df, P = ns). The presence of nodal micrometastases detectable only by immunocytochemistry in patients with Dukes' B colorectal cancer does not justify reassignment to a more advanced disease stage.

The utility of immunocytochemistry in invasive adenocarcinoma of the cervix

The purpose of the study was to evaluate the utility of immunocytochemistry in the management of cervical adenocarcinoma. Patterns of reactivity to various immunocytochemical markers were correlated with clinically known risk factors for recurrence. A retrospective evaluation of 55 patients with invasive cervical adenocarcinoma was conducted. Monoclonal antibodies were generated against various human intermediate filament proteins and tested on fixed, paraffin-embedded tissue by the avidin-biotin complex immunoperoxidase method. Dako V9 antivimentin antibodies and two anticytokeratin antibodies, 35 beta H11 and 34 beta E12, were used. Polyclonal antibodies to carcinoembryonic antigen and antibodies to epithelial membrane antigen were used. Of 55 patients, 50 (91%) had positive epithelial membrane antigen antibodies in tumor cells. Tissue from patients with cervical adenocarcinoma demonstrated positivity for 35 beta H11 antibodies in 46 of 53 patients (87%) and positivity for 34 beta E12 antibodies in 15 of 54 patients (28%). Vimentin antibodies were negative in all except one patient. Carcinoembryonic antigen-positive antibodies were detected in 37 of 55 patients (67%). This study also demonstrated consistent negative expression of vimentin in invasive cervical adenocarcinoma. Carcinoembryonic antigen expression rates were 50% and 75% for patients with small tumors (less than or equal to 2 cm) and large tumors (greater than 2 cm), respectively (p less than 0.01). Patients with carcinoembryonic antigen expression are at increased risk for recurrence and also sustain reduced survival potential. Patients with cervical adenocarcinoma and carcinoembryonic antigen expression are at increased risk for recurrence. We speculate that immunocytochemistry may detect lymph node micrometastases otherwise unsuspected by conventional microscopy.

Effectiveness of immunohistochemical techniques in the detection of lymph node micrometastases of cervical squamous cell carcinoma

Out of a total of 1050 lymph nodes from patients with clinical squamous carcinoma, 58 lymph node metastases related to 18 patients were detected with H&amp;E staining, while 61 lymph node metastases related to 19 patients were observed by immunohistochemical methods. However, by re-staining the original H&amp;E sections with an anti-keratin antibody, the same 58 lymph node metastases were seen. Therefore, the three metastases emerged only in deeper sections which had been used for the immunohistochemical examination. It is suggested that the detection of micrometastases in lymph nodes may be improved by examining several sections at different levels rather than by immunohistochemical methods, even though these facilitate the observation of small groups of neoplastic cells.

Demonstration of Two Ovarian Tumor-Associated Antigens in Primary and Metastatic Breast, Gastric, and Colonic Tumors

The presence of two ovarian tumor-associated antigens (TAAs) defined by monoclonal antibodies BC3 and CC4 in primary and metastatic breast, gastric, and colonic malignant tumors was determined by immunohistochemistry. The BC3 TAA was present in all gastric, colonic, and breast tumors, typically with a large proportion of tumor cells expressing antigen. The CC4 TAA was present in most of these tumors, generally with a lower proportion of tumor cells expressing antigen compared with that of BC3. Both of these TAAs were found in some epithelial cells in normal breast, stomach, and colon, however, the location of the two TAAs in normal tissue was different. With the use of both antibodies, an increase in the number of tumor cell-positive lymph nodes was found in patients with breast, gastric, colonic, and ovarian tumors, including detection of micrometastases in nodes from patients considered node negative on purely morphologic grounds. Immunohistochemical detection of micrometastases derived from adenocarcinomas appears to be superior to purely morphologic detection.