Abstract 5276: Epithelial mesenchymal transition may contribute to anaplastic change of pancreatic ductal adenocarcinoma
Authors: Miura Kotaro , Kimura Kenjiro , Amano Ryosuke , Yamazoe Sadaaki , Ohira Go , Nishio Kohei , Shibutani Masatsune , Sakurai Katsunobu , Nagahara Hisashi , Toyokawa Takahiro , Kubo Naoshi , Tanaka Hiroaki , Muguruma Kazuya , Otani Hiroshi , Yashiro Masakazu , Maeda Kiyoshi , Ohira Masaichi , Hirakawa Kosei 
Published: August 2015

Introduction: Anaplastic pancreatic cancer (APC) is a rare subtype of pancreatic ductal adenocarcinoma (PDA). The prognosis of APC is poorer than that of ordinary PDA. There is no established therapeutic strategy as well as PDA. In this study, we compared the expression of molecular markers in intratumoral different lesions which are undifferentiated lesion (UL) and ductal lesion (DL) to reveal progression pattern of APC and hold important clue for the therapy of APC.

Materials & Methods: Formalin fixed paraffin embedded blocks were made from the primary APC tissues obtained from 6 patients. Each block was manipulated for staining with Hematoxylin and Eosin (H&E) and immunohistochemistry (IHC) for SOX9, E-cadherin, vimentin, ZEB-1, Snail, N-cadherin, CD24 and CD44. Using H&E slice, each sample was divided from cancerous lesion and non-cancerous lesion. Furthermore, cancerous lesion were divided from DL and UL. And then, for each marker, the intensity of staining of UL was compared with that of DL. The intensity was scored from 0 to 3. The relation between DL and UL was estimated based on the intensity score of each sample.

Results: The proportion of DL to all cancerous lesion was 0.5% to 32%. The score of SOX9 was all 3 except one case in both lesions. Although the expression of E-cadherin was almost negative in UL, DL showed various scores. About vimentin, the intensity in UL was largely 2 and 3. In contrast, that of DL was very weak or none. The score of ZEB1 was 0 or 1 in DL and 1 or 3 in UL. Although Snail showed various scores in both regions, the score was mostly higher in UL than in DL. The score of N-cadherin expression was comparatively high in UL. CD24 and CD44 were not almost expressed in DL. In UL, the expression of these markers were various intensity.

Disscusion: In the current study, it was suggested that APC might be derived from PDA by showing the expression of SOX9. Previous studies were reported from the view of KRAS mutation and cytokeratin expression about the origin of APC. However, recent studies were reported that these markers were often expressed even in other pancreatic neoplasm. Furthermore the expression of SOX9 is only identified in PDA among pancreatic neoplasms.

Also, it was suggested that UL might change from DL through EMT by confirming the difference of the expression pattern of markers relating EMT in DL and UL.

Because the expression of CD24 and CD44 varied in each case, it is unclear whether the stemness concerned with the progression to APC in our study. We also need to estimate the other stem cell markers including CD133, Oct3/4 or Nanog.

Conclusion: It was suggested that EMT might induce the progression from PDA to APC.

Citation Format: Kotaro Miura, Kenjiro Kimura, Ryosuke Amano, Sadaaki Yamazoe, Go Ohira, Kohei Nishio, Masatsune Shibutani, Katsunobu Sakurai, Hisashi Nagahara, Takahiro Toyokawa, Naoshi Kubo, Hiroaki Tanaka, Kazuya Muguruma, Hiroshi Otani, Masakazu Yashiro, Kiyoshi Maeda, Masaichi Ohira, Kosei Hirakawa. Epithelial mesenchymal transition may contribute to anaplastic change of pancreatic ductal adenocarcinoma. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 5276. doi:10.1158/1538-7445.AM2015-5276