A. Newtson

A predictive model for serous epithelial ovarian cancer chemo-response using clinical characteristics

One of the prognostic factors most highly associated with ovarian cancer survival is response to initial chemotherapy. Current prediction models of chemo-response built with comprehensive molecular datasets, like The Cancer Genome Atlas (TCGA), could be improved by including clinical and outcomes data designed to study response to treatment. The objective of this study was to create a prediction model of ovarian cancer chemoresponse using clinical-pathological features, and to compare its performance with a similar TCGA clinical model.

p53 mutation status is a primary determinant of placenta-specific protein 1 expression in serous ovarian cancers

Placenta-specific protein 1 (PLAC1) expression is co-opted in numerous human cancers. As a consequence of PLAC1 expression, tumor cells exhibit enhanced proliferation and invasiveness. This characteristic is associated with increased aggressiveness and worse patient outcomes. Recently, the presence of the tumor suppressor p53 was shown in vitro to inhibit PLAC1 transcription by compromising the P1, or distal/cancer, promoter. We sought to determine if this phenomenon occurs in primary patient tumors as well. Furthermore, we wanted to know if p53 mutation influenced PLAC1 expression as compared with wild-type. We chose to study serous ovarian tumors as they are well known to have a high rate of p53 mutation. We report herein that the phenomenon of PLAC1 transcription repression does occur in serous ovarian carcinomas but only when TP53 is wild-type. We find that mutant or absent p53 protein de-represses PLAC1 transcription. We further propose that the inability of mutant p53 to repress PLAC1 transcription is due to the fact that the altered TP53 protein is unable to occupy a putative p53 binding site in the PLAC1 P1 promoter thus allowing transcription to occur. Finally, we show that PLAC1 transcript number is significantly negatively correlated with patient survival in our samples. Thus, we suggest that characterizing tumors for TP53 mutation status, p53 protein status and PLAC1 transcription could be used to predict likely prognosis and inform treatment options in patients diagnosed with serous ovarian cancer.

Clinicopathological predictors of chemoresponsiveness in epithelial ovarian cancer: a preliminary institutional study

Objective: One-third of women with epithelial ovarian cancer are resistant to standard platinum-based chemotherapy, and insufficient data exist in predicting response to chemotherapy. We describe the clinical and pathological factors of patients with complete and incomplete response to treatment. Method: In this retrospective study, data was reviewed from 75 medical charts of 243 patients with primary epithelial ovarian cancers as a preliminary study. All patients underwent chemotherapy and cytoreductive surgery for primary disease. Fifty-six patients had complete response (CR) to chemotherapy and 19 had incomplete response (IR). Fifty-eight and 17 patients had optimal and suboptimal cytoreductive surgery, respectively. Clinical and pathological factors were compared in patients with complete and incomplete response to treatment, and optimal and suboptimal surgery. Overall survival (OS), cancer-specific survival (CSS), and time to recurrence (TTR) were estimated using the Kaplan-Meier method for patient groups. Results: The majority of patients in both the CR and IR groups were diagnosed at advanced stage ovarian cancer. The CR group had significantly lower preoperative CA125 and was more likely to have optimal chemotherapy. The CR group was also more likely to have lymph nodes removed during cytoreductive surgery. A significantly lower percentage of CR patients died from the disease and had statistically longer disease free survival. Patients who underwent suboptimal surgery had significantly shorter survival, but no difference existed in the time until recurrence between patients with optimal and suboptimal surgery. OS, CSS, and TTR were significantly increased in the CR group and in patients that had optimal surgery. Conclusion: Complete response during treatment and optimal surgery significantly increases OS, CSS, and TTR. Preoperative CA125 and lymph node removal during surgery may be predictive of complete treatment response.