Stromal Palladin Expression Is an Independent Prognostic Factor in Pancreatic Ductal Adenocarcinoma

It has been clear that cancer-associated fibroblasts (CAFs) in the tumor microenvironment play an important role in pancreatic ductal adenocarcinoma (PDAC) progression. However, how CAFs relate to the patients' prognosis and the effects of chemoradiation therapy (CRT) has not been fully investigated. Tissue microarrays (TMAs) representing 167 resected PDACs without preoperative treatment were used for immunohistochemical studies (IHC) of palladin, alpha-smooth muscle actin (SMA), and podoplanin. Correlations between the expression levels of these markers and clinicopathological findings were analyzed statistically. Whole sections of surgical specimens from PDACs with and without preoperative CRT, designated as the chemotherapy-first group (CF, n = 19) and the surgery-first group (SF, n = 21), respectively, were also analyzed by IHC. In TMAs, the disease-specific survival rate (DSS) at 5 years for all 167 cases was 23.1%. Seventy cases (41.9%) were positive for palladin and had significantly lower DSS (p = 0.0430). alpha-SMA and podoplanin were positive in 167 cases (100%) and 131 cases (78.4%), respectively, and they were not significantly associated with DSS. On multivariable analysis, palladin expression was an independent poor prognostic factor (p = 0.0243, risk ratio 1.60). In the whole section study, palladin positivity was significantly lower (p = 0.0037) in the CF group (5/19) with a significantly better DSS (p = 0.0144) than in the SF group (16/22), suggesting that stromal palladin expression is a surrogate indicator of the treatment effect after chemoradiation therapy

Comparative genetic analysis of a rare synchronous collision tumor composed of malignant pleural mesothelioma and primary pulmonary adenocarcinoma

Background: Although asbestos acts as a potent carcinogen in pleural mesothelial and pulmonary epithelial cells, it still remains unclear whether asbestos causes specific and characteristic gene alterations in these different kinds of target cells, because direct comparison in an identical patient is not feasible. We experienced a rare synchronous collision tumor composed of malignant pleural mesothelioma (MPM) and primary pulmonary adenocarcinoma (PAC) in a 77-year-old man with a history of long-term smoking and asbestos exposure, and compared the DNA copy number alteration (CNA) and somatic mutation in these two independent tumors. Methods: Formalin-fixed paraffin-embedded (FFPE) tissues of MPM and PAC lesions from the surgically resected specimen were used. Each of these MPM and PAC lesions exhibited a typical histology and immunophenotype. CNA analysis using SNP array was performed using the Illumina Human Omni Express-12_FFPE (Illumina, San Diego, CA, USA) with DNA extracts from each lesion. Somatic mutation analysis using next-generation sequencing was performed using the TruSeq Amplicon Cancer Panel (Illumina). Results: The CNA analysis demonstrated a marked difference in the frequency of gain and loss between MPM and PAC. In PAC, copy number (CN) gain was detected more frequently and widely than CN loss, whereas in MPM there was no such obvious difference. PAC did not harbor CNAs that have been identified in asbestos-associated lung cancer, but did harbor some of the CNAs associated with smoking. MPM exhibited CN loss at 9p21.2-3, which is the most common genetic alteration in mesothelioma. Conclusion: In this particular case, asbestos exposure may not have played a primary role in PAC carcinogenesis, but cigarette smoking may have contributed more to the occurrence of CN gains in PAC. This comparative genetic analysis of two different lesions with same amount of asbestos exposure and cigarette smoke exposure has provided information on differences in the cancer genome related to carcinogenesis

CTNNB1 mutational analysis of solid-pseudopapillary neoplasms of the pancreas using endoscopic ultrasound-guided fine-needle aspiration and next-generation deep sequencing

Solid-pseudopapillary neoplasm (SPN), a rare neoplasm of the pancreas, frequently harbors mutations in exon 3 of the cadherin-associated protein beta 1 (CTNNB1) gene. Here, we analyzed SPN tissue for CTNNB1 mutations by deep sequencing using next-generation sequencing (NGS). Tissue samples from 7 SPNs and 31 other pancreatic lesions (16 pancreatic ductal adenocarcinomas (PDAC), 11 pancreatic neuroendocrine tumors (PNET), 1 acinar cell carcinoma, 1 autoimmune pancreatitis lesion, and 2 focal pancreatitis lesions) were analyzed by NGS for mutations in exon 3 of CTNNB1. A single-base-pair missense mutations in exon 3 of CTNNB1 was observed in all 7 SPNs and in 1 of 11 PNET samples. However, mutations were not observed in the tissue samples of any of the 16 PDAC or other four pancreatic disease cases. The variant frequency of CTNNB1 ranged from 5.4 to 48.8 %. Mutational analysis of CTNNB1 by NGS is feasible and was achieved using SPN samples obtained by endoscopic ultrasound-guided fine needle aspiration

Independent prognostic factors for disease-specific survival on multivariable analysis.

<p>Independent prognostic factors for disease-specific survival on multivariable analysis.</p

Disease-specific survival analysis of PDAC patients who underwent surgery after CRT based on palladin expression level.

<p>In a subanalysis of the chemotherapy-first group, palladin-positive cases have significantly shorter disease-specific survival after surgery.</p

Prognostic factors for disease-specific survival and disease-free survival on univariate analysis.

<p>Prognostic factors for disease-specific survival and disease-free survival on univariate analysis.</p