Can molecular markers help predict outcome in pseudomyxoma peritonei?

Abstract

455 Background: Pseudomyxoma peritonei (PMP) is a rare malignancy characterized by mucinous ascites and peritoneal tumors. Cytoreductive surgery (CRS) with or without intraperitoneal hyperthermic perfusion (IPHP) is considered the mainstay of therapy, but prognosis is variable. Due to its rarity, data on molecular phenotype is lacking and the impact on outcome is unknown. The goal of our study is to correlate molecular markers with outcome in PMP. Methods: A retrospective analysis of cases treated at the University of Cincinnati was performed and tumors analyzed. Medical records were reviewed for clinical, demographic and outcome data. Immunohistochemical studies were performed on formalin fixed paraffin embedded tissue using antibodies to Ki-67, cyclin D, and EGFR. Tumor cells were microdissected from H&E stained sections using laser capture microdissection and DNA was extracted. Exon 1 of K-ras gene was amplified by PCR and then directly sequenced. Data were analyzed using SPSS. Results: Of 22 patients (pts) included in this study 16 (73%) had an appendix primary and 6 (27%) colon. There were 12 females (55%) and 20 (90%) pts were white. Mean age was 53 (29-74) years. Most pts had prior surgery (18, 82%). Complete resection (>99% of visible disease) was achieved in 15 (68%) pts while 17 pts (77%) underwent IPHP. Nine pts had known recurrence (41%) and median time to recurrence (TTR) was 21(+/- 0.398) months (mo). There was one confirmed death and median survival could not be calculated. K-ras mutation was seen in 13 (60%), cyclin-D1 in 9 (41%) and EGFR in 10 (45%) cases. High Ki-67 (>51%) was seen in 8 cases. On univariate analysis median TTR was 15 and 43 mo for pts with high and low Ki-67 (p=0.1); 21 and 43 mo for K-ras positive and negative mutation (p=0.16), 43 and 15 mo for EGFR positive and negative tumors (p=0.6). TTR was 21 mo for cyclin D1 positive as well as negative. Conclusions: Pts with PMP who have undergone CRS and IPHP can have prolonged survival but relapses are common. Our study highlights the possible role of molecular markers such as EGFR and K-ras in tumorigenesis. A potential role in prognosis is being validated in a larger study. Future treatment strategies should incorporate molecular testing to enhance our understanding of PMP. No significant financial relationships to disclose.