Cd44(Cell Adhesion Molecule) Expression in Gastric Adenocarcinoma-Prognostic Importance. A Study of 50 Cases.

Gastric Carcinoma Is The Second Most Common Malignancy Among Men And Third Most Common Among Women In Asia And Also Worldwide (1). Frequency Of Gastric Carcinoma Varies Much With Different Geographic Locations. The Symptoms And Signs Of The Gastric Carcinoma Are Often Reported Late When The Disease Is Already In Advanced Stages (2). Though The Incidence Of Gastric Carcinoma Is Decreasing Nowadays, It Is Still The Second Leading Cause Of Cancer Related Deaths (3). The Major Causes Of Mortality In Case Of Gastric Carcinoma Even After A Curative Resection Are Recurrence And Metastasis. The 5-Year Survival Rate Is Less Than 30% In Developed Countries And Around 20% In Developing Countries (4). Gastric Adenocarcinoma Comprises 95% Of The Total Malignancies Of Stomach. Multiple Genetic And Epigenetic Alterations Are Known To Involve Oncogenes, Tumor Suppressor Genes, Cell Cycle Regulators, Cell Adhesion Molecules And Are Implicated In The Multistep Carcinogenesis Of Human Gastric Carcinoma(8). HISTOLOGICAL AND ANATOMICAL CLASSIFICATION OF GASTRIC CANCER: Several Classification Systems Have Been Proposed To Delineate Gastric Cancer On The Basis Of Both Macroscopic As Well As Microscopic Patterns Of Growth. Different Classification System Includes Borrman, Stout, Japanese System, Ming, World Health Organization (WHO) System And Lauren’s Method. Of Which WHO And Laurens Are The Two Most Commonly Used Classification Systems (5). Treatment Of Choice For Any Resectable Gastric Cancer Is, Surgical Therapy Which Could Be Total Gastrectomy, Subtotal Gastrectomy Or Proximal Gastrectomy. The Choice Of Procedure Depends On The Location Of Tumor And The Ability To Achieve Tumor Free Surgical Margins. The Current TNM Staging Classified Nodal Metastasis Based On Number Of Positive Nodes, In Which It Advocates A Minimum Of 15 Lymph Nodes To Be Resected And Examined For Staging To Be Accurate. Here Comes The Extended D2 Resection Procedure Which Offers Better Survival Advantage Compared With Other Surgical Resections Without Lymphadenectomy(7). Though With The Availability Of Advanced Methods Of Surgical Techniques, It Is Still Common To See Patients With Recurrence In Many Cases. Despite Knowing That Gastric Carcinoma Is Not Very Sensitive To Current Chemotherapy Agents, Most Of Them Are Considered As Palliative In Order To Reduce The Tumor Burden, To Provide Symptomatic Relief And For Better Survival Time. Post Operative Adjuvant Chemotherapy Can To Some Extent Decrease The Rate Of Recurrence. Though We Know That Gastric Carcinoma Is Prone For Recurrence, Even With Curative Resection And Modern Chemotherapeutic Drugs, No Molecular Biomarker Is Currently Available To Predict Gastric Carcinoma Recurrence Before / After Resection. Frequent Cause Of Death In Gastric Carcinoma Are Recurrence And Metastasis. Metastasis Is Initiated Primarily By The Loss Of Adhesion That Renders The Cancer Cells To Leave The Site Of Origin, And Subsequently Reach The Distant Sites Such As Lymph Nodes, Liver, Or The Peritoneum To Form Secondary Cell Colonies (9). Interaction Between The Cells And Also Between The Cell And The Extracellular Matrix Is Strictly Regulated By Cell Adhesion Molecules. Any Breakthrough In This Property Of Cell Adhesion Molecules Allow The Process Of Tumor Progression And Metastasis(10). CD44 Is A Principal Cell Surface Receptor For Hyaluronic Acid. Hyaluronic Acid Is A Major Component Of Extracellular Matrix. Increased Expression Of CD44 By The Tumor Cells Leads To Avid Binding With The Hyaluronan In The Matrix, Thereby Helping In Communication Of Cell-Matrix Interactions Into The Cell Which Is Known As Outside-In Signalling(10). CD44 Plays A Role In Carcinogenesis, Differentiation, As Well As Lymph Node Metastasis Which Are Considered To Be Prognostic For Carcinomas Of Various Organs Such As Lung , Breast , Pancreas, Gastrointestinal Tract Including Gastric Cancer. It Is Considered As A Determinant Of Metastatic And Invasive Behavior(11). As The Literature Suggests, CD44 Is One Of The Factor That Shows Better Association With Initiation And Progression Of Gastric Cancer And Also Plays Major Role In Diagnosis, Therapy As Well As In Prognosis. The Objective Of This Study Is To Identify The Role Of An Adhesion Protein CD44 In The Genesis Of Gastric Carcinoma. The Primary Techniques That Help To Evaluate The Presence And Degree Of CD44 Expression Are Immunohistochemistry, Fluorescence Cell Sorting, And Reverse Transcriptase Polymerase Chain Reactions. Research On CD44 Has Been Active But Fragmented, And It May Offer Newer Therapeutic Approach To Gastric Cancer. While Clinical Predictive Factors, Such As Tumor Staging, Can Predict Recurrence Of Advanced Gastric Cancer, Some Group Of Molecular-Based Biomarkers Like CD44 Which Is A Cell Adhesion Molecule Can Serve As A Useful Predictor For Recurrence Of Advanced Gastric Cancer After Curative Resection And It Has Some Possible Predictive Relevance In Future Clinical Practice