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Hepatocellular adenoma (HCA) is a benign liver tumor composed of hepatocytes.1 HCA represents a heterogeneous entity, and is subclassified into four groups according to genotype and phenotype: hepatocyte nuclear factor (HNF) 1α-inactivated HCA, β-catenin-activated HCA, inflammatory HCA, and unclassified HCA.1 Theses subtypes vary greatly in their clinical and pathological features. Identifying the HCA subtype is important because it represents a way to understand the prognosis of HCA in terms of hepatocellular carcinoma (HCC) transformation. We present a case of β-catenin-activated HCA and discuss the histopathological findings with a review of the literature.

Regulated intramembrane proteolysis of epithelial cell adhesion molecule (EpCAM) results in shedding of the extracellular domain (EpEX) and release of the intra-cellular domain (EpICD) into the cytoplasm. Released EpICD associates with FHL2, β-catenin and Lef-1 to form a nuclear complex and triggers oncogenic signaling. This study was conducted to examine the nuclear expression of EpICD in hepatocellular carcinoma (HCC) and to assess the role of EpICD in HCC. EpICD immunoexpression was examined in 100 cases of HCC using tissue microarrays and correlated with clinicopathological parameters. We also examined the role of EpICD in HCC using EpICD cDNA transfected HCC cell line and EpCAM silenced HCC cell line by small interfering RNA (siRNA). Nuclear expression of EpICD was observed in 19 of 100 (19%) cases. Nuclear expression of EpICD significantly correlated with nuclear expression of β-catenin, and Ki-67 labeling index. In addition, nuclear expression of EpICD was associated with higher histologic grade and advanced T category. Forced overexpression of EpICD in the HCC cell significantly increased the cell proliferation, migration and invasion. The overexpression of EpICD also increased the expression levels of the active form of β-catenin and c-myc and cyclin D1. In contrast, downregulation of EpCAM by siRNA decreased the cell proliferation, migration, invasion and the expression of active form of β-catenin, c-myc and cyclin D1. Our present data suggest that EpICD plays important roles in HCC progression by modulating expression of target genes of EpCAM.

The tumor-to-tumor metastasis is a rare event. The lung tumors are the most common donor tumors in tumor-to-tumor metastasis, but are exceedingly rare as a recipient. Here, we report a case of papillary thyroid carcinoma (PTC) metastasizing to adenocarcinoma in situ (AIS, formerly bronchioloalveolar carcinoma) of the lung in a 44-year-old woman who underwent total thyroidectomy for PTC 8 years ago. To the best of our knowledge, the present case is the first case reporting on PTC metastasized to AIS. A review of the relevant literature is presented.

Although the expression of keratin 7 (K7) and K20 is considered to be a useful factor in the differential diagnosis of intrahepatic cholangiocarcinoma (ICC) and metastatic colorectal carcinoma (CRC) of the liver, a proportion of typical ICC retains K20 expression. The frequency and biological significance of K20 expression in ICC remains unclear. We analyzed the expression of K7, K19 and K20 in 66 surgically resected liver tumors consisting of 46 ICCs and 20 metastatic CRCs of the liver and 20 corresponding primary CRCs. In the 46 ICCs, K7, K19 and K20 were expressed in 40 (87%), 45 (98%) and 16 (35%) cases, respectively. K7, K19 and K20 were expressed in 1 (5%), 20 (100%) and 16 (80%) of the 20 primary CRCs and 2 (10%), 20 (100%) and 16 (80%) of the 20 metastatic CRCs, respectively. A combined K7/K20 profile was identified as a good predictor for differentiating ICC and metastatic CRC. K20 expression in ICC was significantly associated with male gender (P=0.034), hilar location (P=0.026), intraductal papillary type (P=0.006), intestinal phenotype (P

Fibromatoses comprise many different entities of well-differentiated fibroblastic proliferation with variable collagen production and form a firm nodular mass. Abdominal fibromatosis is distinguishable from other forms of fibromatosis because of its location and its tendency to occur in women of childbearing age during or following pregnancy. Abdominal fibromatosis in children is an extremely rare condition. A 15-month-old boy presented with an abdominal wall mass that had recently increased in size. Mass excision was perfomed. The tumor was 4.3×4.1 cm and partly circumscribed. Histologically, the tumor was composed of parallel long fascicles of spindle-cells with a uniform appearance. The edges of the resected mass were infiltrative, and the surgical margins were positive. Mitotic figures were

The endoplasmic reticulum (ER) is an essential intracellular organelle that serves important cellular functions. One of its major functions is to ensure proper folding of newly synthesized proteins destined for secretion, the cell surface, or intracellular organelles. Various physiological and pathological conditions lead to the accumulation of unfolded proteins in the ER, a condition referred to as "ER stress." In response to ER stress conditions, cells activate an intracellular signaling pathway, the unfolded protein response (UPR),1,2 which acts to reduce ER stress by activating three adaptive pathways: 1) transcriptional induction of ER chaperones to help protein folding; 2) translational attenuation of protein synthesis, which blocks new protein synthesis; and 3) enhanced degradation of misfolded or unfolded proteins via the ubiquitin-proteasome system.1,3 If the UPR is unable to rescue cells, the cells eventually enter apoptosis via increased C/EBP homologous protein (CHOP) expression or activation of ER-specific caspases. CHOP, also known as growth arrest and DNA damage-inducible protein 153 (GADD153), is a transcription factor induced by DNA damage and is activated in response to ER stress.4 CHOP plays an important role in ER stress-induced apoptosis and is widely used as an ER stress marker. Moreover, increased CHOP expression has been reported in some malignant tumors.5-7 On the other hand, p53 is one of the important apoptosis-related genes and is also involved in many other cellular processes such as cell cycle progression, DNA repair, differentiation, senescence, and chromatin remodeling.8 Impaired p53-dependent apoptosis due to high-risk human papillomavirus (HR-HPV) has been known as one of the key mechanisms of cervical carcinogenesis. Interestingly, CHOP is one of the many p53 target genes9,10 according to human cell studies. Cervical cancer is the second most common type of cancer in women worldwide.11 Human papillomaviruses (HPV) are the etiologic agents responsible for cervical cancer. Over 100 different types of HPV have been identified based on their DNA sequence.12 HPV types such as HPV 16 and HPV 18 are high oncogenic risk types. More than 99% of cervical cancers contain DNA from at least one HR-HPV type, and approximately 70% contain HPV 16 or 18.13 However, experimental and epidemiological evidences indicate that HR-HPV is not sufficient to induce tumor development. Other factors have to be involved in the progression of infected cells to full neoplastic transformation. Recent studies have shown that ER stress may facilitate viral replication or pathogenesis.14 The ER is an essential organelle for viral replication and maturation. A large number of viral proteins are produced in infected cells, where unfolded or misfolded proteins activate the ER stress response. There are some reports regarding the role of ER stress in HPV infection. Accordingly, ER stress responses were repressed in HPV 16 infected genital keratinocytes.15 ER protein 57 (ERp57), one of the ER stress markers, was induced in HPV 16 positive squamous cell carcinoma (SqCC) of uterine cervix.16 Based on these reports, we hypothesized that CHOP is involved in the carcinogenesis of uterine cervical cancer in association with HR-HPV and/or p53. To test this, we conducted immunohistochemical studies to assess CHOP and p53 expression in cervical intraepithelial neoplasms (CIN) and invasive SqCC of the uterine cervix. We also investigated the association between CHOP expression and HR-HPV infection.