[A Case of Goblet Cell Adenocarcinoma Incidentally Diagnosed after Appendectomy That Required Additional Bowel Resection with Lymph Nodes Dissection].

A 54-year-old male presented to the clinic, complaining of dull lower abdominal pain that started a day ago. There was a tenderness on right lower quadrant on palpation and abdominal computed tomography(CT)showed that dilated appendix with a diameter of 12 mm. The patient was diagnosed with acute appendicitis and laparoscopic appendectomy was performed on the same day. The tip of the appendix was swollen and looked purple, gangrenous appendicitis findings were identified. However, histopathology detected GCA on resected appendix with positive surgical margin and additional tumor resection was indicated. Laparoscopic ileocecal resection with D3 lymph nodes dissection was performed 24 days after the first surgery. Resected specimen showed that the stump of the appendix was palpable as a mass in the orifice of the appendix and histopathology revealed the remnant of the appendiceal GCA. No lymph nodes tumor metastasis was identified. Chromogranin A and synaptophysin were positive and Ki-67 was approximately 50%. According to the guideline of neoadjuvant chemotherapy for colon cancer, oral 5-fluorouracil therapy was performed for half a year after the second surgery and the patient remains still healthy without recurrence 1 year after the surgery. Here, we experienced a rare case of GCA of the appendix that was detected incidentally after appendectomy for acute appendicitis.

[A Case of Monomorphic Epitheliotropic Intestinal T-Cell Lymphoma Causing Perforation of the Small Intestine].

Monomorphic epitheliotropic intestinal T-cell lymphoma(MEITL)is very rare and aggressive subtype of lymphoma with poor prognosis. A 60-year-old man complaining of abdominal pain was underwent partial resection of the jejunum for panperitonitis with a small intestinal perforation. The histopathological and immunohistochemical findings led to the diagnosis of MEITL. Postoperative course was uneventful. One month after the operation, the patient was scheduled for 6 courses of CHOP regimens. He presented with bowel obstruction twice during the 3 courses of CHOP. As the recurrence of MEITL could not be ruled out, diagnostic laparoscopy was performed. Laparoscopic findings revealed no recurrence and adhesive small bowel obstruction. The patient was followed closely without treatment after 6 courses of CHOP. The patient has been alive without recurrence 18 months after the resection. We reported a case of monomorphic epithelial intestinal T- cell lymphoma causing jejunal perforation.

Expression level of long noncoding RNA H19 of normotensive placentas in late pregnancy relates to the fetal growth restriction.

AIM: Infants with fetal growth restriction (FGR) are at an increased risk of perinatal morbidity and mortality. The long noncoding RNA H19 gene is expressed abundantly in placental villi and recent studies suggest that it regulates FGR. However, the role of H19 in the FGR placenta remains unclear. This study aimed to clarify the relationship between H19 expression and FGR using normotensive placentas after 34 weeks of gestation. METHODS: Formalin-fixed paraffin-embedded tissues from human placentas collected from pregnancies resulting in small for gestational age (SGA) and appropriate for gestational age (AGA) newborns were used. The histopathological features of placenta tissues, such as villous stromal fibrosis, the numbers of terminal villi, villous vessels and cytotrophoblasts were analyzed using hematoxylin and eosin, Masson's trichrome staining and immunostaining. The localization and expression of H19 in the placentas were demonstrated by in situ hybridization and reverse transcription-quantitative polymerase chain reaction (RT-qPCR), respectively. Moreover, the expression levels of H19-regulated molecules such as IGF2 and decorin (DCN) were measured by RT-qPCR. RESULTS: Histopathological features of the placental villous were not different between placentas associated with SGA and AGA. H19 localized to the villous stroma, endothelial cells and cytotrophoblasts. Moreover, the expression level of H19 in SGA placentas was significantly lower than that in AGA placentas. The expression levels of IGF2 and DCN in SGA placentas tended to be lower than those in AGA placentas similarly to H19. CONCLUSION: This study highlights the potential importance of regulatory events mediated by H19 in SGA placentas without histopathological abnormalities in late pregnancy.

Farnesoid X receptor induces cell death and sensitizes to TRAIL-induced inhibition of growth in colorectal cancer cells through the up-regulation of death receptor 5.

Farnesoid X receptor (FXR) exhibits critical anti-cancer functions in several types of cancer, including colorectal cancer, in vitro and in vivo. However, the underlying mechanism remains unclear. We evaluated pharmacological activation of FXR with the synthetic agonist GW4064 using comprehensive proteomic analysis in colorectal cancer cell lines (HCT116, SW480, and DLD1). Among the commonly detected proteins in all three cell lines, death receptor 5 (DR5) was the most up-regulated protein, and key autophagy-related proteins, such as microtubule-associated protein 1 light chain 3 alpha/beta (MLP3A/3B) and p62 sequestosome-1 (SQSTM), were also differentially expressed. Western blot analysis showed that GW4064 stimulation induced activation of the extrinsic death signaling pathway in all cell lines and induced activation of the intrinsic death signaling pathway in DLD1 cells. Western blotting showed that DR5 up-regulation was associated with inhibition of autophagic activity. These results suggest that FXR activation induced DR5 up-regulation through inhibition of autophagic activity and the DR5-related death signaling pathway. In addition, DR5 selective ligand, also known as TRAIL, has been widely used for anti-cancer treatment in several clinical trials. Co-treatment of TRAIL with GW4064 synergistically inhibited colorectal cancer cell proliferation as compared with single treatments. To the best of our knowledge, our results provide novel insights into FXR function in cancer cell lines. These findings may contribute to a new therapeutic strategy for colorectal cancer.

Relationship between genetic alterations and clinicopathological characteristics of papillary thyroid carcinoma.

Papillary thyroid carcinoma (PTC) is characterized by proliferation of follicular cells with distinctive nuclear features such as ground glass appearance, nuclear groove and pseudoinclusion. From the proliferation pattern, PTC is divided into several histological subtypes; conventional histology is classified as papillary type, and there are also follicular and solid variants. PTC is heterogeneous in genetic alterations. PTC with BRAF mutation presents a histology of conventional PTC, and follows an aggressive clinical course. Most cases of PTC with RAS mutation show a follicular variant, and prognosis is favorable. RET/PTC1 is observed sporadically and in young cases, and prognosis is favorable. RET/PTC3 is associated with radiation exposure, and the solid variant is frequent. ETV6-NTRK3 may be associated with radiation exposure, and the clinical course is aggressive. Mutation in the telomerase reverse transcriptase promoter is observed in PTC cases involving elderly male patients. Tumor size is large, associated with distant metastasis and advanced stage. This mutation is found concomitantly with BRAF mutation, and the clinical course is aggressive. Genetic alterations form subsets of PTC with distinct clinicopathological features. Careful assessment of clinicopathological features is considered useful in predicting clinical course and when planning treatment.

2-Deoxy-d-glucose increases GFAT1 phosphorylation resulting in endoplasmic reticulum-related apoptosis via disruption of protein N-glycosylation in pancreatic cancer cells.

The glycolytic inhibitor 2-deoxy-d-glucose (2DG) causes energy starvation, affecting cell viability in a wide range of cancer cell lines. To determine the action of 2DG in pancreatic cancer, we performed proteomic analysis of pancreatic cancer cell line after 2DG treatment. Eighty proteins showed differential expression and among these, proteins involved in phosphohexose metabolism were upregulated. Up-regulation of glutamine: fructose 6-phosphate aminotransferase 1 (GFAT1), which belongs to the hexosamine biosynthesis pathway (HBP) that produces uridine diphosphate N-acetylglucosamine (UDP-GlcNAc) to maintain glycoprotein, was validated by evaluation of mRNA and protein levels. Therefore, we assessed the amounts of total N-glycoproteins. Unexpectedly, we found a reduction of total N-glycoproteins and phosphorylation of GFAT1 by AMP-activated protein kinase (AMPK). These data may shed light on HBP dysfunction. Furthermore, we found endoplasmic reticulum (ER) stress accompanied by increased expression of ER stress markers, such as glucose response protein 78 (GRP78) and C/EBP-homologous protein (CHOP), in 2DG-treated cells. Moreover, the additive activation of AMPK by metformin (Met) synergistically enhanced the reduction of protein N-glycosylation and cell growth inhibition in the presence of 2DG. These results suggest that 2DG reduces N-glycosylation of proteins following the increase of phosphorylation of GFAT1 and results in the inhibition of cell growth mediated by ER stress in pancreatic cancer cells.

A case of ulcerative colitis with squamous cell carcinomas and multiple foci of squamous dysplasia.

Squamous cell carcinoma (SqCC) in ulcerative colitis (UC) is rare. A 38 year-old Japanese woman, who suffered from left-sided UC for 18 years, underwent total colectomy due to SqCCs in the rectum and the sigmoid colon. They were well differentiated SqCC, and metastasis was found in the paracolic lymph nodes. Multiple small foci of squamous dysplasia (SD) were noted in the rectal mucosa. Glandular dysplasia was not found. TP53 was not detected in SD. Approximately 40% of cells were immunostained with TP53 in SqCC, however no mutation was found in TP53 gene. Human papilloma virus and Epstein Barr virus were negative in SD and SqCCs. The patient is free of the disease at one and half years after surgery and chemotherapy. SD may be a precursor of SqCC. It appeared that TP53 does not play a vital role in the development of SqCCs in the current case. Careful attention should be paid to SD in UC patients. Viral infection may need to be examined. The pathogenesis of SqCC in patients of UC needs to be elucidated.

"Wild type" GIST: Clinicopathological features and clinical practice.

Gastrointestinal stromal tumor (GIST) is a mesenchymal tumor of the gastrointestinal tract. Mutation of KIT and PDGFRA genes is implicated in the tumorigenesis. Approximately 10% of GISTs do not harbor mutation of these genes, and they are designated as "wild type" GIST. They are classified into succinate dehydrogenase (SDH)-deficient and non-SDH-deficient groups. SDH-deficient group includes Carney triad and Carney Stratakis syndrome. The patients are young women. Tumors occur in the antrum of the stomach, and tumor cells are epithelioid. Lymph node metastasis is frequent. The non-SDH-deficient group includes neurofibromatosis (NF) type 1 and GISTs with mutations of BRAF, KRAS, and PIK3CA and with the ETV6-NTRK3 fusion gene. GIST in NF occurs in the small intestine, and tumor cells are spindle shaped. GIST with BRAF mutation arises in the small intestine. Attention to the age, gender, family history and other neoplasms may raise the prediction of syndromic disease. Location of the tumor, morphology, and pleomorphism of the tumor cells are further informative. Lymphovascular invasion should be carefully evaluated. The determination of KIT expression is essential for the diagnosis. When wild type GIST is suspected, intensive genetic analysis is required. Further, a careful and long-time observation is recommended.

DNA damage response and its clinicopathological relationship in appendiceal tumors.

BACKGROUND: Appendiceal tumors are rare, and their pathogenesis is not well known. DNA damage response (DDR) is a sequence from the detection of damaged DNA to the repair, and its impairment is implicated in the progression of cancers. The aim of the current study is to explore the expression and phosphorylation of checkpoint kinase 2 (Chk2) and TP53, which are key molecules in DDR, and their clinicopathological correlation in the appendiceal tumors. METHODS: Chk2, phosphorylated Chk2 (pChk2), and TP53 were immunostained in 4 cases of adenoma (AD), 5 non-mucinous adenocarcinomas (AC), 29 low-grade appendiceal mucinous neoplasms (LAMN), and 7 mucinous adenocarcinomas (MAC). Ki-67 labeling index was also evaluated by immunostaining. RESULTS: Chk2 was highly expressed in the nuclei of all the appendiceal tumors. While pChk2 was high in AD, LAMN, and MAC, it was reduced in AC. Nuclear positive reaction of TP53 was lower in LAMN compared with those of other tumors. The Ki-67 labeling index was slightly lower in LAMN than those in other tumors. The recurrence and death in LAMN is infrequent compared with those in AC and MAC. CONCLUSIONS: The current study suggested the impairment of DDR in AC and MAC. DDR appeared to be preserved in LAMN, and it may account for low proliferating activity and a favorable clinical course in LAMN.

Focal ground glass opacity of the lung in metachronous prostate and gastric cancer: A case report.

Chest computed tomography (CT) revealed a focal ground glass opacity (GGO) with a minimal solid area in a 75-year-old man. The shadow was located in the periphery of the right upper lobe and measured 11 mm in diameter. The patient had a medical history of metachronous prostate and gastric cancers. The patient had been treated with androgen deprivation therapy for prostate cancer for 12 years and underwent subtotal gastrectomy for triple gastric cancers 7 months before. Since primary lung adenocarcinoma was suspected, CT-assisted percutaneous needle biopsy was performed. Histology revealed the sheet-like and trabecular proliferation of atypical cells, suggesting that the lesion was moderately to poorly differentiated adenocarcinoma. Adenocarcinoma cells showed subepithelial extension causing the thickening of alveolar walls. A tumor thrombus was not detected in the blood or lymphatic vessels. Immunohistochemistry revealed that carcinoma cells were negative for cytokeratin 7 (CK7), CK20, thyroid transcription factor-1 and CDX2 and positive for prostate-specific antigen and P504S. Based on these findings, the patient was diagnosed with metastatic carcinoma from prostate cancer. The disease remained stable for 4 months after the diagnosis, and no new lesions were observed on chest CT. Metastatic carcinoma rarely presents with focal GGO. Lung biopsy is necessary to identify the pathology of the lesion, and the primary site needs to be confirmed by immunohistochemistry with specific markers, particularly in a case of metachronous multiple cancers. A tumor thrombus, which is suggestive of lymphangitic carcinomatosis or pulmonary tumor thrombotic microangiopathy, also needs to be evaluated.

VIP and calcitonin-producing pancreatic neuroendocrine tumor with watery diarrhea: clinicopathological features and the effect of somatostatin analogue.

CONTEXT: Pancreatic neuroendocrine tumor (pNET) secretes various peptide hormones; however, calcitonin hypersecretion is rare. Its clinicopathological significance and treatment is still controversial. CASE REPORT: A 43 year-old Japanese man presented severe watery diarrhea and a large mass in the pancreatic tail. Blood concentration of VIP was elevated to 649 pg/mL (reference range: 0-100 pg/mL), and calcitonin to 66,700 pg/mL (reference range: 15-86 pg/mL). There was no tumor in other endocrine organs. The resected tumor was composed of 80% calcitonin-positive cells and 10% VIP-positive cells. After the operation, the levels of VIP and calcitonin were decreased to 44 and 553 pg/mL, respectively, and diarrhea was improved. The mRNA of somatostatin receptor (SSTR) subtypes 2, 3 and 5 in the tumor tissue were increased 22.8, 25.1, and 37.0-fold of those of normal pancreas, respectively. At 19 months after the operation, blood calcitonin was again raised to 3,980 pg/mL, and metastatic tumors were found in the liver. With the treatment of long-acting somatostatin analogue, calcitonin was reduced to 803 pg/mL. The patient does not present endocrine symptom, and the size of the metastatic tumors appears stable. CONCLUSION: From the world literature to date, co-secretion of VIP and calcitonin was documented in only 10 cases of pNET including the current case. Although VIP is a primary cause of diarrhea in these cases, high level of calcitonin may also influence on the clinical symptoms. Somatostatin analogue suppresses the levels of VIP and calcitonin, and the control proliferation is also expected when tumor cells express SSTRs.

Central Nervous System-related Graft-versus-host Disease after Allogeneic Hematopoietic Stem Cell Transplantation.

Allogeneic hemopoietic stem cell transplantation (allo-HSCT) is the only curative therapy for refractory hematological malignancies. However, there are many treatment-related complications, including organ disorders, graft-versus-host disease (GVHD), and infectious diseases. Furthermore, there are many unclear points regarding central nervous system (CNS) complications, and the prognosis in patients with CNS complications is extremely poor. We herein report a 49-year-old woman who developed CNS-GVHD after a second transplantation for therapy-related myelodysplastic syndrome. CNS-GVHD in this case was refractory to all treatments, including steroids, and progressed. We also present a review of the literature about the symptoms, diagnosis, and treatment of CNS-GVHD.

Characteristics of non-neoplastic epithelium that appears within gastric cancer with and without Helicobacter pylori eradication: A retrospective study.

A non-neoplastic epithelium (NE) often appears in gastric cancer (GC). We explored the histological features of NE in comparison between HP-eradicated and HP-infected GCs. We enrolled 40 HP-eradicated and 40 HP-infected GCs matched by size, macroscopic and histological type. NE was classified into full gland type and surface type; the former was a non-neoplastic gland isolated within cancer, and the latter was NE on the surface of the cancer. Surface type was additionally divided into NE at the cancer margin (marginal surface type) and NE inside cancer (internal surface type). The primary endpoints were the frequency and the length ratio (the ratio to cancer length) of NE. The secondary endpoints were the relationships between NE and clinicopathological factors, including endoscopic findings of a gastritis-like appearance (GLA), reddish depressed lesion (RDL), and white nodular mucosa (WNM). The frequency and length ratio of the internal surface type in HP-eradicated GCs were significantly higher (82.5% vs 50%, P = 0.005) and larger (11.6 ± 10.6 vs 4.2 ± 9.9, P < 0.001) than those in HP-infected GCs, and the increase was more significant according to the passage of time since HP eradication. The frequency and length ratio of marginal surface type and full gland type were not significantly different between the two groups, but the coexistence of internal surface and full gland types was statistically significant (p < 0.001). The frequencies of GLA, RDLs, and WNM in HP-eradicated GCs were significantly higher than those in HP-infected GCs. GLA-positive GCs were covered more widely by internal surface type than GLA-negative GCs (13.3% vs. 6.6%, P = 0.003). Various types of NE were noted in gastric cancer, and the internal surface type of NE was shown to be significantly linked to HP-eradicated cancer and GLA.

Inhibitor for protein disulfide-isomerase family A member 3 enhances the antiproliferative effect of inhibitor for mechanistic target of rapamycin in liver cancer: An in vitro study on combination treatment with everolimus and 16F16.

mTOR is involved in the proliferation of liver cancer. However, the clinical benefit of treatment with mTOR inhibitors for liver cancer is controversial. Protein disulfide isomerase A member 3 (PDIA3) is a chaperone protein, and it supports the assembly of mTOR complex 1 (mTORC1) and stabilizes signaling. Inhibition of PDIA3 function by a small molecule known as 16F16 may destabilize mTORC1 and enhance the effect of the mTOR inhibitor everolimus (Ev). The aim of the present study was to elucidate the usefulness of combination treatment with Ev and 16F16 in liver cancer using cultured Li-7 and HuH-6 cells. The proliferation of cultured cells was examined following treatment with 0.01 µM Ev, 2 µM 16F16 or both. The expression levels and phosphorylation of S6 kinase (S6K) and 4E-binding protein 1 (4E-BP1) were examined by western blotting. Li-7 was susceptible to Ev, and proliferation was reduced to 69.5±7.2% by Ev compared with that of untreated cells. Proliferation was reduced to 90.2±10.8% by 16F16 but to 62.3±12.2% by combination treatment with Ev and 16F16. HuH-6 cells were resistant to Ev, and proliferation was reduced to 86.7±6.1% by Ev and 86.6±4.8% by 16F16. However, combination treatment suppressed proliferation to 57.7±4.0%. Phosphorylation of S6K was reduced by Ev in both Li-7 and HuH-6 cells. Phosphorylation of 4E-BP1 was reduced by combination treatment in both Li-7 and HuH-6 cells. Immunoprecipitation assays demonstrated that PDIA3 formed a complex with 4E-BP1 but not with S6K. The small molecule 16F16 increased susceptibility to Ev in cultured liver cancer cells, which are resistant to Ev. The inhibition was associated with reduction of 4E-BP1 phosphorylation, which formed a complex with PDIA3. Combination treatment with Ev and 16F16 could be a novel therapeutic strategy for liver cancer.

[An adult with chronic active Epstein-Barr virus infection associated with repeated liver dysfunction].

A 30-year-old woman with hepatitis for 5 months was admitted to our hospital. She had been given a diagnosis of liver dysfunction 2 years previously, and the hepatitis in this case was believed to be drug-induced. On admission, the patient was asymptomatic. Serologic tests for hepatitis A, B, and C were negative, and the laboratory results showed a WBC count of 7600/mm3 (lymphocytes, 85%), an AST level of 559 U/L, ALT level of 427 U/L, and EBV-DNA of 2.9x10(6) copies/microg DNA. Histopathological examination of the liver biopsy specimens revealed moderate lymphocyte infiltration in the sinusoids and positive Epstein-Barr-encoded RNA (EBER) -lymphocytes. Therefore, chronic active Epstein-Barr virus infection (CAEBV) was diagnosed. However, 9 months after the diagnosis she died of mycotic sepsis. We presume that the patient may have developed CAEBV at the prior diagnosis of liver dysfunction 2 years previously. Therefore, CAEBV associated with liver dysfunction should be considered during the differential diagnosis of patients showing persistent liver dysfunction.

High Expression of p21 as a Potential Therapeutic Target in Ovarian Clear-cell Carcinoma.

BACKGROUND/AIM: DNA damage response (DDR), wherein p21 is a cell fate determinant, is a potential cancer therapeutic target. Molecular expression during DDR was explored in ovarian clear-cell carcinoma (CCC). MATERIALS AND METHODS: CHK1, CHK2, TP53 and p21 expression in DDR was examined using immunostaining in surgical sections of CCC (n=22). Molecular alterations in two types of CCC cell lines, JHOC-5 and JHOC-9, were investigated using western blot analysis. RESULTS: Expression of DDR-associated molecules was noted in most patients. While high p21 expression was found in half of the patients, the remaining patients exhibited low p21 expression. Treatment with UC2288, a p21 inhibitor, attenuated proliferation of both cell lines, more prominently in JHOC-9, resulting in reduced viability and subsequent apoptosis. CONCLUSION: p21 Inhibitor induced cell death in cells with high p21 expression, suggesting that p21 suppression can be a therapeutic strategy to treat patients with CCC.

Three cases of follicular pancreatitis: association between radiological findings and pathological features.

Follicular pancreatitis (FP) is characterized by nodular mass composed of lymphoid hyperplasia and fibrosis. We here present radiological and pathological features of three cases of FP. The three patients were middle- or old-aged men, and nodular mass was pointed out at health examination. Computed tomography failed to demonstrate a mass. Magnetic resonance imaging demonstrated a mass in each case. 18F-fluorodeoxyglucose positron-emission tomography (FDG-PET) demonstrated two nodular masses with high standardized uptake value (SUV) in two cases and single mass in one case. The pathological examination disclosed two lesions with fibrosis and hyperplastic lymphoid follicles in two cases and one lesion in one case. Masses with high SUV appeared to correspond with the lesions of FP. Compared with the features of FDG-PET images of pancreatic ductal carcinoma, multiple lesions with high SUV favor a diagnosis of FP rather than pancreatic cancer. FDG-PET is useful for the diagnosis of FP.

Small cell carcinoma with skeletal muscle differentiation of urinary bladder.

Reported herein is a case of small cell carcinoma (SCC) with skeletal muscle differentiation of urinary bladder in a 76-year-old woman presenting macrohematuria. Ultrasonography and CT detected a mass at the anterior wall of the urinary bladder, and total cystectomy followed. The tumor consisted of solid growth of small round cells with high nucleocytoplasmic ratio admixed with rhabdoid cells with eosinophilic cytoplasmic inclusions, invading the perivesical tissue. On immunohistochemistry the tumor cells were diffusely positive for neural markers and CD99, and sporadically for skeletal muscle markers. Fluorescence in situ hybridization showed no translocation of EWS. The patient died from massive recurrence in the pelvis 4 months after operation. This rare tumor indicates a potential of myoid differentiation in SCC of the urinary bladder and differential diagnosis from primitive neuroectodermal tumor is important because the treatment is different.

[A case report--gastric stenosis due to primary gastric malignant lymphoma after administration of R-CHOP].

A 67-year-old man was diagnosed with primary gastric malignant lymphoma by an endoscopic examination. Endoscopy revealed irregular ulcerative regions from body to antrum of the stomach. With a diagnosis of diffuse large B-cell lymphoma based on the biopsy finding, the patient was treated with R-CHOP chemotherapy. After three cycles of chemotherapy, a tight stenosis was located at the antrum of the stomach. Total gastrectomy was performed due to an obstruction. Pathological diagnosis was complete response. It was thought that the tumor organization rapidly disappeared due to the effectiveness of the chemotherapy, and that the origin of the stricture caused fibrosis.

Histology and molecular biology studies on the expression and localization of angiopoietin-like protein 8 in human tissues.

Angiopoietin-like protein (ANGPTL) 8 regulates the partitioning of triglycerides by inhibiting lipoprotein lipase in muscle and adipose tissues. ANGPTL8 is expressed in the liver and adipose tissue and secreted into the blood. However, the precise localization of ANGPTL8-expressing cells in these tissues remains unknown. The aim of the present study was to investigate the localization of ANGPTL8-expressing cells in human tissues. Using formalin-fixed paraffin-embedded human tissue specimens, the expression of ANGPTL8 was investigated by reverse transcription-quantitative polymerase chain reaction (RT-qPCR), immunohistochemistry (IHC) and in situ hybridization (ISH). The expression level of ANGPTL8 mRNA was the highest in the liver, followed by lipoma, hibernoma and normal adipose tissue. In the liver, wild type (KF809856) and two splice variants of ANGPTL8 mRNA (KF809857 and KF809858) were found to be expressed. The expression level of the splice variant KF809858, which produces a short form of ANGPTL8, accounted for <1% of ANGPTL8 in the liver. IHC revealed that ANGPTL8 was expressed in hepatocytes in zone 1 of the hepatic acinus in the liver. In the adipose tissue, mature adipocytes weakly expressed ANGPTL8, while immature adipocytes strongly expressed it. ISH confirmed ANGPTL8 mRNA expression in portal hepatocytes and immature adipocytes. ANGPTL8 was expressed in the cells, which actively uptake and metabolize triglycerides. In hibernoma, the ANGPTL8 protein and mRNA were homogeneously expressed in tumor cells. The expression of ANGPTL8 was associated with the differentiation state and activity of lipid metabolism in a subpopulation of cells in the liver and adipose tissue. The association may be helpful for the understanding of local metabolic state in organs and diseases associated with the lipid metabolism.