Detection And Clinical Significance Of Lymph Nodes Micrometastasis In Patients With Gastric Cardia Adenocarcinoma

Background and objective: Gastric cardia adenocarcinoma (GCA) is one of the most common malignant disease in Northern China. A remarkable epidemiological characteristic for GCA is its very similar geographic distribution with esophageal squamous cell carcinoma. The incidence rate of tumors of distal gastric has descended obviously from 1980s, but the incidence rate of GCA still keeps in high level. There are several differences between GCA and distal gastric cancer in respect of epidemiology, risk factors, histogenesis and clinical characteristics. Therefore GCA should be categorized as a clinically distinct disease. Lymph node metastases leads to relatively high mortality rate for GCA after operation. Micrometastasis is defined as microscopical deposit of malignant cells, less than 2mm in diameter and it is missed on conventional histological examination. The detection of lymph node metastases is very importance for clinical staging, comprehensive treatment after operation and evaluated prognosis. CD44 is a kind cell adhesion molecules that correlated with invasion and metastasis of tumor cell. Cytokeratin (CK) proteins serve as reliable markers for the epithelial origin of cells because they are essential constituents of the cytoskeleton of both normal and malignant epithelial cells. The present study was to examine the lymph nodes micrometastasis in GCA with negative nodes by routine pathological examination with two markers of CK19 and CD44v6, to investigate the micrometastasis characteristics in GCA and evaluate the relationship between micrometastasis and clinicopathological features.Materials and methods: A total of 349 lymph nodes were obtained from 45 GCA patients who underwent gastrectomy in the first affiliated hospital of Henan university of science and technology from 2004 to 2005. The postoperative patients were histological classified pN0 with routine hematoxylin-eosin (HE) staining. In the meantime, 42 cases were given follow-up study. Moreover, the lymph nodes from 10 patients with benign gastric tumors and the lymph nodes with positive by HE staining from 2 patients with GCA were obtained as control group. The anti-CK19 and anti-CD44v6 monoclonal antibody were used to examine micrometastasis in this assay. Micrometastasis was defined as single tumor cell or cluster of tumor cells that were negative in HE staining but were detected by immunostaining with anti-CK19 or anti-CD44v6. Clinicopathological data were analyzed by statistical method.Results: Routine examination by HE staining examined node-negative in all the 349 lymph nodes from 45 patients with GCA. Micrometastasis was found in 33 lymph nodes (9.46%) from 15 patients (33.33%). 33 lymph nodes from 15 patients were positive for CK19, 27 lymph nodes (7.74%) from 12 patients (26.67%) were positive for CD44v6. In control group, the negative lymph nodes by HE staining with benign gastric tumors were also negative by immunostaining with CK19 and CD44v6, the positive lymph nodes by HE staining with GCA were also positive by immunostaining with CK19 and CD44v6. The micrometastasis in lymph node was related with the depth of invasion (P<0.05) and Lauren classification (P<0.01), but not related with age, sex, tumor size and differentiation (P>0.05). Fifteen of those patients (33.3%) were up-staged (fromâ… A stage toâ… B stage in 1 patient, fromâ… B stage toâ…¡stage in 2 patients, fromâ…¡stage toâ…¢A stage in 9 patients and fromâ…¢A stage toâ…£stage in 3 patients). In 42 patients followed up, a higher incidence micrometastasis was found recurrent patients (7/15) compared with result from recurrent-free patients (1/27, P<0.01). The 2-year survival rate was significantly lower for patients with lymph node micrometastasis(63.64%) than for those without lymph node micrometastasis(95.65%, P=0.011).Conclusions: It is necessary to detect the micrometastasis in GCA with negative lymph node by routine examination. CK19 and CD44v6 can be indicator for detection of micrometastasis. The detection of micrometastasis could increase the accuracy of staging for tumor and may be helpful in clinical comprehensive treatment. Micrometastasis might correlate with worse prognosis for patients with GCA.