Abstract
BackgroundAlthough postoperative adjuvant chemoradiotherapies prevent recurrence for some patients with ampullary cancer, the recurrence rate is as high as 29 % in patients with stage I cancer. In an effort to identify predictors of recurrence in patients with ampullary adenocarcinoma, we investigated the clinical value of assessing standard and variant forms of CD44.MethodsImmunohistochemistry staining and reverse-transcription polymerase chain reaction (RT-PCR) was used to detect standard and variant forms of CD44 in samples of ampullary adenocarcinoma. The cDNA microarray analysis comparing tumors with or without pancreatic invasion was undertaken and analyzed by Ingenuity Pathway Analysis.ResultsThe standard CD44 (CD44s) isoform was detected in 76 of 98 patients with ampullary adenocarcinoma, and the negative or weak expression of CD44s was correlated with pancreatic invasion, lymphovascular invasion, advanced stage and bone metastasis. Moderate to dense expression of CD44s was correlated with shorter overall survival in patients with localized cancer (T1 or T2 disease, P = 0.0268). The patients with advanced cancer (T3 or T4 disease) and moderate or dense CD44s expression had a trend toward better survival. Alternative splicing of CD44 was confirmed using RT-PCR, which revealed that the CD44ν3-10 isoform was only expressed in patients with cancer recurrence. Fold change of CD44ν6-10 was also increased. In addition, networks containing CD44, vascular endothelial growth factor (VEGF), epidermal growth factor receptor (EGFR), transforming growth factor-β (TGF-β), matrix metalloproteinase 2 (MMP2), AKT, extracellular signal-regulated protein kinase 1 and 2 (ERK1/2), p38 MAPK, activated protein 1 (AP1)‚ and CTNNB1 were constructed after comparing microarray data from patients with and without pancreatic invasion.ConclusionsWhereas CD44s functions as tumor-promoting oncoprotein in early localized ampullary adenocarcinoma, CD44 variants are expressed in advanced cancer and patients with recurrence. Regional invasiveness and distant metastasis of ampullary cancer is controlled by a complex interacting network.Electronic supplementary materialThe online version of this article (doi:10.1186/s12885-015-1924-3) contains supplementary material, which is available to authorized users.
Highlights
Postoperative adjuvant chemoradiotherapies prevent recurrence for some patients with ampullary cancer, the recurrence rate is as high as 29 % in patients with stage I cancer
standard CD44 isoform (CD44s) expression was correlated with recurrence and survival in ampullary adenocarcinoma patients In 94 patients with regular follow-up, 60 patients developed recurrence and some patients had recurrence in two or more regions
The pancreaticobiliary type of ampullary adenocarcinoma predicts poor prognosis in some study [4]; the histological type was not correlated with poor survival in Because CD44s expression was correlated with pancreatic invasion (Table 1), which was a predictor for poor prognosis in a previous study [3], we grouped the patients according to pancreatic invasion to omit its’ interference
Summary
Postoperative adjuvant chemoradiotherapies prevent recurrence for some patients with ampullary cancer, the recurrence rate is as high as 29 % in patients with stage I cancer. Postoperative adjuvant chemoradiotherapies may prevent cancer recurrence for some patients [5], the recurrence rate is 54 % after multimodality treatment and is as high as 29 % in patients with stage I ampullary cancer [6]. Increased expression of CD24 is found in ampullary carcinomas than ampullary adenoma or normal mucosa of periampullary duodenum [12]. CD44, CD133, CD166‚ and EpCAM are considered markers of CSCs in colorectal cancer [10], and their expression is increased in ampullary carcinoma as compared with ampullary adenoma or normal mucosa [13]
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