Study Of Preoperative EUS Stage And Relationship With Invasion And Metastasis In Gastric Carcinoma

IntroductionGastric cancer is one of the most encountered malignances. .It has been accepted that accurate preoperative staging is not only important for prediction of the prognosis, but also essential to establishment of individualized cancer therapy.The staging was previously made by analysis on the bases of clinical presentations, laboratory test results, and various imaging findings such as trans-abdominal B-mode Ultrasonography, computed tomography (CT) or magnetic resonance imaging (MRI). However, precise conclusion was often difficult to obtain due to limitations on or local unavailability of these techniques themselves.Endoscopic ultrasonography (EUS) was first introduced by a Germen doctor in the early 1980s and is now used worldwide. The ability of EUS to accurately visualize and differentiate the different layers of the gut wall makes it possible to determine the penetration depth of a gastrointestinal cancer more precisely. Simultaneously, the observation of the evolvement of lymph nodes and other organs adjacent to the cancer within the range of EUS scanning can provide more detailed additional information to the disease.Currently, EUS is becoming one of the routine methods in staging of gastrointestinal cancers, including gastric carcinoma.Published data showed that the accuracy of T and N staging for gastric cancer is 78-92% and 63-78 %, respectively, being imperative in prognostic prediction and especially in decision making regarding to individualized therapeutic regimens.It has been noticed that overstaging and understaging are the common problems encountered in current EUS practice,and accuracy for lymph node staging exhibits discrepancy between observers. Current study was aimed to evaluate the usefulness of EUS in TNM staging of gastric cancer by comparing EUS preoperative staging results with pathological findings, and the preliminary exploration of possible reasons for above-mentioned phenomenon was especially intended.Meantime, Immunohistochemistry was used to measure the expression of PETN,MMP-2 and CD_44V6 in gastric cancer .The relationship was analysised between the preoperative EUS staging and the expression rate of PTEN,MMP-2 and CD_44V6.Materials1 .Patients : A total of 74 patients with histologically confirmed gastric cancer were referred to EUS and stageed preoperatively by using the TNM system.2.Primary agents and instruments: The concentrated monoclonal antibodies against PTEN,MMP-2, CD_44V6 were used, whose concentration were 1:75,1:100, 1:100 respectively, as well as the immunohistochemistry PV-9000 kits. And those routine agents and instruments used in immunohistochemistry.MethodsA total of 74 patients with histologically confirmed gastric cancer were referred to EUS and stageed preoperatively by using the TNM system. And the staging results of endoscopic ultrasonography were compare with the histopathological staging. Immunohistochemistry was used to measure the expression of PTEN,MMP-2 and CD_44V6 in gastric cancer .The relationship was analysised between the preoperative EUS staging and the expression rate of PTEN,MMP-2 and CD_44V6.The data was statistical analyzed by SPSS 13.0. The level of significancer was set at P<0.05.Results1. The overall accuracy of EUS for determination of the T stage was 82.5%, and for T1, T2, T3, and T4 were 100%, 72.8%, 85% and 78.9%, respectively. For N stage, EUS had the accuracy of 74.3%, with sensitivity and specificity of 82.4% and 56.5%, respectively. 2. The preoperative EUS for T and N staging of gastric cancer was of inversely correlation with the expression rate of PTEN ,and was of positive correlation with the expression rate of MMP-2 and CD_44V6(P<0.05).DiscussionClinical experience with EUS used as an important preoperative staging tool for gastric cancer has been widely reported.Our reports for accuracy of T stage of EUS was 82.5%, and for T1, T2, T3, and T4 were 100%, 72.8%, 85% and 78.9%, respectively. For N stage, EUS had the accuracy of 74.3%, with sensitivity and specificity of 82.4% and 56.5%, respectively.EUS is an accurate staging modality in most cases, with a few exceptions of overstaging and understaging. In our study, 13 incorrectly staged patients consisted of ulcerated type in 7 cases, protruded type in 4, and flat type in 1. By careful examination and analysis, we found pathologically that reasons contributing to overstaging can be misinterpretation of necrostic tissue overlaying the ulcer surface, scars and fibrosis, inflammatory reaction in the peripheral structure of cancer, thickened gastric wall. Microscopic cancer invasion or focal destruction of a certain layer undetectable with lower frequency ultrasound often results in understaging.Inaccuracy of N stage may be as the result of lack of reliable differential standard for benign and malignant nodes.The diameter, location, and the distance of lymph node to the primary lesion, and the endoscopists' expertise are important as well. Other factors affecting the accuracy may also include the frequency and penetration depth of the transducers used.PTEN is a tumor suppressor gene. The expression rate of PTEN in gastric cancers was lower than in normal gastric tissues obviously, and reduced with increased invasive depth and clinical stages, reduced histological differentiation and occurring of lymphatic and long distance metastasis. The degradation of extracellular matrix and basement membrane is the key progress in invasion and metastasis of cancers.The substrates of MMP-2 are fibrous framework molecules of extracellular matrix and basement membrane,and type IV collagen can be degradated by MMP-2. CD44 is a group of cell surface adhesion molecules involved in cell-cell and cell-matrix interactions. CD44 spliced variants 6(CD44V6)have been found to enhance the metastatic potential of gastric cancer. The role of CD44V6 as a prognostic marker and predictor of metastatic potential in gastric carcinomas has been reported.Our study shows that the preoperative EUS for T and N staging of gastric cancer was of inversely correlation with the expression rate of PTEN ,and was of positive correlation with the expression rate of MMP-2 and CD_44V6 . The preoperative EUS for T and N staging could well display the molecular pathologic basis of gastric carcinoma.Conclusion1. EUS is an accurate staging modality in determining cancer invasive depth and lymph node involved, with a few exceptions of overstaging and understaging.Patients with gastric cancers can benefit from preoperative EUS staging for establishing individualized therapy. However,EUS criteria to differentiate benign from malignant nodes still need to be further defined by future studies.2. The preoperative EUS for T and N staging could well display the molecular pathologic basis of gastric carcinoma.