Mesothelin as a New Tumor Marker for Ovarian Cancer
Mesothelin as a New Tumor Marker for Ovarian Cancer
Ovarian cancer became a more and more important disease in recent years due to its first
 mortality rate of gynecologic malignancies. The incidence of ovarian cancer also increased in
 recent year in Taiwan. The lack of symptoms, difficulties in early diagnosis, insufficient
 accurate tumor markers, and lack of information about ovarian tumor biology contribute to the
 poor prognosis in ovarian cancer patients. The prognostic parameters for ovarian carcinomas
 are tumor stage, histologic subtype, degree of malignancy, and residual tumor after surgical
 treatment. However, these factors present an incomplete picture of the tumor biology of
 ovarian cancer and are frequently interrelated. Thus, the identification of new biologic
 factors predictive of individual disease course and prognosis would be extremely useful.

 Detection of tumor markers that are released into the circulation can aid in the diagnosis
 and/or monitoring of therapeutic responses of patients with various tumors, including
 carcinomas of ovary. CA125 is the most commonly used serum marker for patients with ovarian
 carcinoma. Although it has proven clinically valuable in monitoring the response of patients
 to therapy, some ovarian carcinomas do not express CA125, and CA125 often is increased in
 patients with inflammatory disease. Thus, there is a need for improvement, either in the form
 of a more specific and/or sensitive assay or an assay that uses a different marker and can be
 used to complement CA125 toward the goal to improve patient survival by improving diagnosis.

 Mesothelin is a 40-kDa glycosylphosphatidylinositol-linked glycoprotein. In normal tissues,
 the expression of mesothelin has subsequently been shown to be largely restricted to
 mesothelial cells, although immunoreactivity has also been reported in epithelial cells of
 the trachea, tonsil, fallopian tube, and kidney. Mesothelin has been shown to be
 over-expressed in pancreatic carcinomas, gastric carcinoma and ovarian carcinoma, and it
 seems that mesothelin may be utilized as a new tumor marker for ovarian carcinoma. We will
 evaluate that if mesothelin can be a new potential tumor marker for ovarian cancer in this
 proposal.
Incidence of Ovarian Cancer Ovarian cancer is the first mortality rate of gynecologic
 malignancies (1-3) and became a more and more important disease in recent years (4-6). The
 incidence of ovarian cancer also increased in recent year in Taiwan (7). Ovarian cancer has
 the highest mortality of all gynecological cancers, with an overall 5-year survival rate of
 only 20-30% (1). The lack of symptoms, difficulties in early diagnosis, insufficient accurate
 tumor markers, and lack of information about ovarian tumor biology contribute to the poor
 prognosis in ovarian cancer patients (8). The prognostic parameters for ovarian carcinomas
 are tumor stage, histologic subtype, degree of malignancy, and residual tumor after surgical
 treatment (9-12). However, these factors present an incomplete picture of the tumor biology
 of ovarian cancer and are frequently interrelated (13). Thus, the identification of new
 biologic factors predictive of individual disease course and prognosis would be extremely
 useful. From the above-mentioned data, ovarian cancer indeed is a disease that should be
 respected, however, there were only few of research work focusing on it in Taiwan.

 Tumor marker for ovarian cancer Detection of tumor markers that are released into the
 circulation can aid in the diagnosis and/or monitoring of therapeutic responses of patients
 with various tumors, including carcinomas of ovary (14-17), prostate (18), the
 gastrointestinal tract (19, 20), or breast (21). CA125 is the most commonly used serum marker
 for patients with ovarian carcinoma (14). Although it has proven clinically valuable in
 monitoring the response of patients to therapy, some ovarian carcinomas do not express CA125,
 and CA125 often is increased in patients with inflammatory disease. Thus, there is a need for
 improvement, either in the form of a more specific and/or sensitive assay or an assay that
 uses a different marker and can be used to complement CA125 toward the goal to improve
 patient survival by improving diagnosis.

 New potential molecule as tumor marker for ovarian cancer Mesothelin is a 40-kDa
 glycosylphosphatidylinositol-linked glycoprotein. It is synthesized as a precursor of
 molecular mass 69 kDa, which then is proteolytically processed into an N terminal secreted
 form of molecular mass 30 kDa and a membrane-bound form of 40 kDa (22, 23). The 30-kDa
 secreted form has been termed megakaryocyte potentiating factor (23). In normal tissues, the
 expression of mesothelin has subsequently been shown to be largely restricted to mesothelial
 cells, although immunoreactivity has also been reported in epithelial cells of the trachea,
 tonsil, fallopian tube, and kidney (24). Mesothelin has been shown to be expressed in
 pancreatic carcinomas(25), gastric carcinoma (26) and ovarian carcinoma (27), and it seems
 that mesothelin may be utilized as a tumor marker for ovarian carcinoma.

 We will evaluate the amount of mesothelin in pre- and post-treatment serum samples of
 patients with epithelial ovarian cancer. We will also correlate the clinicopathologic items
 and the prognosis of ovarian cancer patients and evaluate whether mesothelin can be a new
 rumor marker for ovarian cancer patients.
Inclusion Criteria:

 - Patients with ovarian carcinoma who undergo hysterectomy, bilateral
 salpingo-oophorectomy, omentectomy, and appendectomy will be enrolled and the clinical data
 will be obtained from our hospital. All of the patients received four to six courses of
 adjuvant platinum-containing chemotherapy.Histologic grading was according to International
 Union against Cancer criteria (28). The stage of disease was classified according to the
 International Federation of Gynecology and Obstetrics (FIGO, 1987). Pelvic and paraaortic
 lymph node samplings will be performed, if the disease will be confined to within the ovary
 or will be without a ruptured capsule. The histopathologic data, including histologic type
 and histologic grade, will be evaluated by a certified pathologist. The maximal diameter of
 the residual tumor after surgery will be also recorded. All patients will be followed up at
 3-month intervals.

 Patients with ovarian endometrioma, other benign ovarian tumors receiving surgical
 intervention, or healthy patients without surgical intervention will be presented as normal
 controls.

 Exclusion Criteria:

 -