Insulinoma-associated protein 1 (INSM1) is an important biomarker of Achaete-scute homolog-like 1-driven pathways. For diagnosis of pancreatic neuroendocrine tumors (PanNET), chromogranin A (CGA), synaptophysin (SYP), and neural cell adhesion molecule (NCAM) were also considered as potential biomarkers. However, it is often difficult to diagnose it immunohistochemically. Hence, we examined the expression pattern of INSM1 in pancreatic solid tumors. We detected INSM1, CGA, SYP, and NCAM immunohistochemically, in 27 cases of NET [pure type: 25 cases, mixed adenoneuroendocrine carcinoma (MANEC): 2 cases]. We included 5 cases of solid-pseudopapillary neoplasm (SPN), 7 cases of acinar cell carcinoma (ACC), and 15 cases of pancreatic ductal adenocarcinoma (PDAC) as the control group. Nuclear expression of INSM1 was found in all PanNET pure type cases. However, expression of INSM1 was negative in PDAC, ACC, and SPN in all cases, whereas faint expression was seen in the cytoplasm from SPN. MANEC comprises of two components: neuroendocrine carcinoma and adenocarcinoma components. The NET component was positive for INSM1 expression, whereas the PDAC component does not express INSM1, which aids in distinguishing these components. Our results suggest that INSM1 is a useful immunohistochemical marker for diagnosing pancreatic neuroendocrine tumor.

The geriatric nutritional risk index (GNRI) is widely used for nutritional assessment in older inpatients and is associated with postoperative complications and cancer prognosis. We investigated the use of GNRI to predict long-term outcomes in hepatocellular carcinoma of all etiologies after hepatectomy. Overall, 346 patients were examined after propensity score matching. We dichotomized the GNRI score into high GNRI (> 98: N = 173) and low GNRI (≤ 98: N = 173) and evaluated recurrence-free survival (RFS) and overall survival (OS) between both groups. Clinicopathological characteristics between the low- and high-GNRI groups were similar after propensity score matching except for the components of the GNRI score (body mass index and serum albumin level), Child–Pugh score (comprising serum albumin level), and preoperative alpha-fetoprotein level (p < 0.0001, p < 0.0001, p = 0.0030, and p = 0.0007, respectively). High GNRI was associated with significantly better RFS and OS (p = 0.0003 and p = 0.0211, respectively; log-rank test). Multivariate analysis revealed that GNRI is an independent prognostic factor of RFS and OS (low vs. high; hazard ratio [HR], 1.8284; 95% confidence interval [CI] 1.3598–2.4586; p < 0.0001, and HR, 1.5452; 95% CI 1.0345–2.3079; p = 0.0335, respectively). GNRI is an objective, inexpensive, and easily calculated assessment tool for nutritional status and can predict prognosis of hepatocellular carcinoma after hepatectomy.

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We have previously shown that human liver myofibroblasts promote in vitro invasion of human hepatocellular carcinoma (HCC) cells through a hepatocyte growth factor (HGF)/urokinase/plasmin-dependent mechanism. In this study, we demonstrate that myofibroblasts synthesize the serine proteinase inhibitor tissue factor pathway inhibitor-2 (TFPI-2). Despite the fact that recombinant TFPI-2 readily inhibits plasmin, we show that it potentiates HGF-induced invasion of HCC cells and is capable of inducing invasion on its own. Furthermore, HCC cells stably transfected with a TFPI-2 expression vector became spontaneously invasive. HCC cells express tissue factor and specifically factor VII. Addition of an antibody to factor VII abolished the pro-invasive effect of TFPI-2. We suggest that TFPI-2 induces invasion following binding to a tissue factor-factor VIIa complex preformed on HCC cells. Our data thus demonstrate an original mechanism of cell invasion that may be specific for liver tumor cells.Hepatocellular carcinoma (HCC) 1 is one of the most frequent primary tumors in the world (1). It is a major complication of liver cirrhosis, although more rarely it will develop on a noncirrhotic liver. HCC are characterized by a high rate of local, intra-hepatic invasion. HCC are infiltrated by myofibroblastlike cells, located around tumoral sinusoids and in fibrous septa and capsule, when present (2-4). We have previously shown that cultured human liver myofibroblasts strongly promoted in vitro invasion of human HCC cell lines through their secretion of hepatocyte growth factor (HGF) (5). In further studies, we showed that HGF induced invasion by increasing the expression of the urokinase-type plasminogen activator (uPA) by the cancer cells (6). Indeed, myofibroblast-or HGFinduced invasion was dose-dependently blocked by a selective uPA antagonist (6). One of the main functions of uPA is to convert the inactive zymogen plasminogen into plasmin, a broad-spectrum proteinase able to degrade several components of the extracellular matrix and thus a likely effector of cancer cell invasion.Tissue factor pathway inhibitor-2 (TFPI-2), also known as placental protein 5 is a serine proteinase inhibitor containing 3 tandemly arranged Kunitz-type proteinase inhibitor domains, homologous to tissue factor pathway inhibitor (7). TFPI-2 exists as 3 isoforms of 27, 31, and 33 kDa that are synthetic products of a single gene and arise from differential glycosylation. TFPI-2 is a strong inhibitor of plasmin as well as of trypsin, plasma kallikrein, and factor XIa. It does not inhibit uPA (8). TFPI-2 synthesis has been described in dermal fibroblasts and endothelial cells (9 -11). In these cell types, the major part of TFPI-2 is sequestered within the extracellular matrix (ECM), presumably bound to heparan sulfate. In the course of a systematic sequencing of a human liver myofibroblast cDNA library described elsewhere (12), we found that these cells expressed transcripts for TFPI-2. Given the ability of TFPI-2 to inhibit plasmin, we were interest...