Pancreatic carcinosarcoma with the same KRAS gene mutation in both carcinomatous and sarcomatous components: molecular evidence for monoclonal origin of the tumour

Abstract

Aims: To better understand the histogenesis, prognosis and feasible treatment of pancreatic carcinosarcoma, a rare type of neoplasia.

Methods and results: We investigated eight additional cases of pancreatic carcinosarcoma at a single institution, including the clinicopathological, immunohistochemical, and KRAS mutation characteristics. We have also reviewed the current literature on this rare type of neoplasia, and summarized the clinicopathological features and feasible treatments. As a result, concordant strong nuclear immunoreactivity for P53 protein and the same type of KRAS gene mutation, c.35G>A (p.G12D) or c.35G>T (p.G12V), were showed in both carcinomatous and sarcomatous components in five of eight cases. Furthermore, we found that the patients treated with surgery plus postoperative chemotherapy had longer survival than those treated with surgery only (P = 0.034 and P = 0.131 for overall survival and disease-free survival, respectively), although Cox regression multivariate analysis indicated that it was not an independent predictor. In addition, we found KRAS mutant allele-specific imbalance in four of our five cases of pancreatic carcinosarcoma, which was associated with advanced disease and a worse prognosis.

Conclusions: This is the largest panel of cases of pancreatic carcinosarcoma studied so far, including clinicopathological, immunohistochemical and molecular cytogenetic features. Our findings indicate that the tumour could have been of monoclonal origin, and that the sarcomatous components might have arisen from metaplastic transformation of the carcinomatous components. Our results also suggest that surgery plus POC including gemcitabine may be a good choice for patients with pancreatic carcinosarcoma.

Keywords: KRAS mutation; P53; pancreatic carcinosarcoma; postoperative chemotherapy.