Expression of CD44 Alternative Splicing Variants in Primary and Lymph Node Metastatic Lesions of Gynecological Cancer

CD44 is known as an adhesion molecule which is involved in lymphocyte activation and lymphocyte homing. In recent years, its role in the invasion and metastasis of malignant tumors has attracted the attention of investigators.　　 In this study, the expression of CD44 variants was investigated in primary lesions and metastasis into the lymph node in 53 patients with gynecological cancer.　　 The following patients with various types of gynecological carcinoma, established by operation and pre-treatment biopsy, were included in this study: 19 patients with cancer of the uterine cervix, 23 with cancer of the uterine endometrium, and 11 with ovarian cancer. Tissue samples were obtained from a primary lesion and a nodal metastasis of each patient, and immunohistochemical staining was performed by the ABC method through the use of monoclonal antibodies against CD44vl-10. Specimens proving CD44vl-10 positive were then submitted to immunohistochemical staining through the use of monoclonal antibodies against CD44v6 and CD44v9. Expression of CD44v was judged positive when DAB revealed color development, irrespective of the degree of staining intensity.　　 CD44v were all expressed in the cancer cell membrane. In normal endometrium, expression of CD44vl-10 and v9 was observed in the endometrial gland cell membrane. In normal ovarian tissues, CD44v6 and v9 were not detected.　　 The expression of CD44v6 in patients with endometrial cancer was noted in 13 (72.2%) of 18 patients with vascular invasion and in one (20.0%) of 5 patients without it, indicating a significant relation to vascular invasion. It was also remarkably higher in those for whom the invasion exceeded 1/2 of the myometrium than in those for whom the invasion did not exceed 1/2 of the myometrium, and was higher too in advanced stages and in node-positive patients. In one patient, CD44v6 was detected not in the primary lesion but in the nodal metastasis. The expression of CD44v6 in patients with ovarian cancer occurred more frequently in nodepositive patients.　　 Our study results suggest that the expression of CD44v6 in endometrial adenocarcinoma cells is involved in the progression of the carcinoma, nodal metastasis, myometrial invasion, and vascular invasion, and that in ovarian cancer, the expression of CD44v6 is involved in nodal metastasis

RNA splicing alteration in the response to platinum chemotherapy in ovarian cancer: A possible biomarker and therapeutic target

AbstractSince its discovery, alternative splicing has been recognized as a powerful way for a cell to amplify the genetic information and for a living organism to adapt, evolve, and survive. We now know that a very high number of genes are regulated by alternative splicing and that alterations of splicing have been observed in different types of human diseases, including cancer. Here, we review the accumulating knowledge that links the regulation of alternative splicing to the response to chemotherapy, focusing our attention on ovarian cancer and platinum‐based treatments. Moreover, we discuss how expanding information could be exploited to identify new possible biomarkers of platinum response, to better select patients, and/or to design new therapies able to overcome platinum resistance