Long‐term oncological outcomes of ovarian serous carcinomas with psammoma bodies: A novel insight into the molecular pathogenesis of ovarian epithelial carcinoma

Abstract

A two-tier system in which ovarian epithelial carcinomas are subdivided into type I and type II tumors has been proposed on the basis of recent molecular pathogenesis findings. Type I tumors, unrelated to tumor protein p53 (TP53) mutations, show favorable prognosis in a slow step-wise process, whereas type II tumors, related to TP53 mutations, contribute to poor prognosis. Ovarian serous carcinomas with excessive psammoma bodies behave like type I tumors. However, their etiology and prognostic significance remain obscure. The objective of the present study was to evaluate the characteristic features and potential relevance of psammoma bodies to the clinical outcome of 44 patients with serous carcinomas with long-term follow-up. The 5-and 10-year survival rates were significantly different between the serous carcinomas with less than 5% area of psammoma bodies and those at least 5% area (P < 0.01). All tumors with at least 5% area were both diploid and immunohistochemically negative for TP53 mutations. All patients with these tumors, including eight with International Federation of Gynecology and Obstetrics (FIGO) stages III or IV disease, survived more than 5 years and their 10-year survival rate was 76%. In multivariate analysis using clinical parameters, the apparent existence of psammoma bodies was an indication to view serous carcinomas as type I tumors with long-term survival. Our results suggested that the formation of psammoma bodies is associated with increased apoptotic tumor cell death related to normal TP53 function. The pathological findings of psammoma bodies might contribute to the consideration of pathogenesis and to the development of prognostic prediction rules for serous carcinomas. (Cancer Sci 2010; 101: 1550-1556 O varian carcinoma is the fifth leading cause of cancerrelated death and the most lethal malignancy of the female reproductive tract.(1) The clinical outcome of patients with advanced ovarian carcinoma is poor despite aggressive surgery and intensive chemotherapy. Accurate evaluation of the primary tumor is important to determine the prognosis and treatment strategies. Various known prognostic factors such as clinical stage of disease, histological grade, and DNA ploidy have been established in an effort to estimate a patient's individual prognosis and to improve therapeutic strategies in ovarian carcinoma. (2)(3)(4)(5) Shih and Kurman recently proposed a model of ovarian carcinogenesis based on clinical, pathological, and molecular genetic studies.(6) The model divides ovarian carcinomas into two groups designated type I and type II. Type I tumors show favorable prognosis and generally develop from wellestablished precursor lesions or borderline tumors. Type I tumors, including micropapillary serous carcinoma (7) and well-differentiated serous carcinoma, are genetically stable and are characterized by mutations in a number of different genes including v-Ki-ras2 kirsten rat sarcoma viral oncogene homolog (KRAS), v-raf murine sarcoma viral oncogene homolog B1 (BRAF), and v-erb-b2 ery...

The prognostic value of dividing epithelial ovarian cancer into type I and type II tumors based on pathologic characteristics

“…Several studies have investigated the eligibility of a dualistic model for ovarian serous carcinoma [5,[15][16][17][18][19][20][21]. All studies show that a dualistic model for ovarian serous cancer is a significant predictor of survival.…”

“…A number of studies have investigated the prognostic value of dividing serous ovarian cancer in high-and low-grade serous carcinomas from pathological characteristics [7,[15][16][17][18][19][20]. However, only few studies have included the full spectrum of histological subtypes of EOC and a comprehensive number of other prognostic values, when evaluating the putative prognostic value of the two groups [21,22].…”

Hypermetabolic Calcified Lymph Nodes on 18Fludeoxyglucose-Positron Emission Tomography/Computed Tomography in a Case of Treated Ovarian Cancer Recurrence: Residual Disease or Benign Formation?

“…More investigation is required to elucidate their exact nature, their formation mechanism, and whether they are the result or the cause of retardation of tumor growth in ovarian cancer. Although the exact mechanism of psammoma body formation is yet unclear, they are known to be associated with increased apoptotic cell death, BRAF mutation, and normal TP53 function, all of which are more profound in low-grade ovarian serous adenocarcinoma (22,23,24). FDG uptake can occur through inflammatory processes secondary to these mechanisms.…”

Molecular-Biological Characteristics of Type I, Ovarian Low-Grade Serous and Mucinous Carcinomas and Prospects of Molecular-Targeted Therapy

“…The ratio of low-to high-grade serous carcinoma cases among all serous carcinoma cases is 1:9, indicating a very low incidence of low-grade serous carcinoma [6]. Anticancer drug sensitivity of low-grade serous carcinoma is lower than that of highgrade serous carcinoma [5]; however, the clinical prognosis is more favorable than that of high-grade serous carcinoma [7]. These findings might reflect the biological characteristics of the disease, which is a tumor of low malignant potential.…”