Apocrine carcinoma-and-malignant myoepithelioma in a dog: a case of simultaneous malignant progression of both luminal epithelium and myoepithelium.

A 9-y-old male Boxer dog developed a mandibular skin tumor, which histologically had a locally invasive growth pattern composed of bilayered structures of inner eosinophilic cuboidal tumor cells and outer clear polygonal tumor cells with cytoplasm containing glycogen granules. Both cell populations gradually changed from low-grade morphologic features to highly anaplastic ones. Immunohistochemically, the eosinophilic tumor cells were positive for cytokeratin 8, a useful marker for luminal epithelial cells. In contrast, the clear tumor cells expressed several myoepithelial markers, including α-smooth muscle actin, p63, and cytokeratin 14. Based on these histologic and immunohistochemical characteristics, we diagnosed this apocrine sweat gland tumor as a carcinoma-and-malignant myoepithelioma with high-grade transformation of both luminal and myoepithelial cells. Our case may be a helpful reference for the histogenesis of carcinoma-and-malignant myoepithelioma, in which both the luminal epithelial and myoepithelial components are malignant.

Infective endocarditis with systemic bacterial embolism caused by Staphylococcus aureus in a free-ranging Amami rabbit (Pentalagus furnessi).

The Amami rabbit (Pentalagus furnessi) is found only on the two islands of Amami-Oshima and Tokunoshima in southwest Japan. It has a primitive appearance and ecology, is an evolutionarily valuable animal and has been assigned to the International Union for Conservation of Nature Red List of Threatened Species. We describe a case with mild purulent wounds on the distal digital skin of both forelimbs and multiple nodular lesions in various organs, including the heart and kidney. Microscopically, the heart lesions were characterized by disruption of the mitral valve and multifocal myocardial necrosis and abscesses due to infection with gram-positive cocci. Similar bacterial infarctions were also found in other organs, including the kidneys. The bacteria were identified as Staphylococcus aureus by immunohistochemical and molecular biological examinations. This first report of infective endocarditis and systemic infarctions caused by S. aureus in an Amami rabbit indicates the importance of monitoring purulent injuries, even if mild, to prevent secondary infections in this species.

Histological, immunohistochemical and ultrastructural features of polyglucosan bodies in uterine smooth muscle of pet rabbits (Oryctolaguscuniculus).

We document the frequency and morphological and immunohistochemical features of inclusion bodies in uterine smooth muscle cells in 56 (76%) of 74 investigated pet rabbits (Oryctolagus cuniculus). Inclusion bodies began to appear at the age of 2 years and their frequency increased with age (P = 0.047, r = 0.33). They ranged from 5 to 20 µm in diameter, were slightly basophilic to amphophilic with well-delimited oval bodies in haematoxylin and eosin-stained tissue sections and formed in the cytoplasm of the uterine smooth muscle cells with displacement of the cell nuclei. The inclusion bodies were positive with periodic acid-Schiff, Best's carmine, Lugol's iodine and Grocott's methenamine silver methods. They were immunoreactive to a monoclonal antibody raised against human polyglucosan and negative with monoclonal antibodies for several intermediate filament proteins. Electron microscopy revealed that they were non-membranous structures composed of electron-dense amorphous material. The morphological, histochemical, immunohistochemical and ultrastructural features of the inclusion bodies in the rabbi uteri were similar to those of human polyglucosan bodies (PGBs). PGBs appear to occur at a high frequency in the uterus of rabbits, which are known to be susceptible to uterine diseases.

Multiple cystic sphere formation from PK-8 cells in three-dimensional culture.

Three-dimensional (3D) culture of cancer cells mimics the in vivo environment. Recently, we reported that pancreatic ductal adenocarcinoma (PDAC) cell lines with epithelial and mesenchymal features formed differently shaped spheres in 3D culture. However, only PK-8 cells, the epithelial PDAC cell line with the highest E-cadherin expression among the eight PDAC cell lines, formed multiple cystic spheres in 3D culture. Optical coherence tomography revealed interconnected cysts inside the spheres. A weak inter-cellular adhesion, individual cell degeneration, necrosis, and secretory granules in the cytoplasm were observed in the PK-8 spheres using electron microscopy. The expression of MUC1, MUC5AC, and amylase was increased in PK-8 cells in the 3D culture compared with that in 2D culture. These findings suggest that highly E-cadherin-expressing epithelial PK-8 cells form multiple cystic spheres, which may be promoted by enhanced mucin and amylase synthesis in 3D culture.

Adenomatous Hyperplasia of Bowman's Capsule Epithelium in a Dog with Metastatic Nasal and Hepatic Neuroendocrine Carcinoma.

A 12-year-old spayed Shiba dog with a nasal neuroendocrine carcinoma and multiple hepatic nodules was necropsied. Histologically, proliferated blast cells with a monolayer or multilayered structure were observed in the kidney. This blast cell proliferation extended from Bowman's capsule epithelium to the proximal tubule in approximately 3% of nephrons. Immunohistochemistry revealed that blast cells were positive for vimentin, Wilm's tumour protein 1 (WT1), paired box 2 (PAX2) and CD10, but negative for cytokeratin (CK) AE1/AE3, CK19, CAM5.2, synaptophysin and chromogranin A. On the basis of these findings, adenomatous hyperplasia of Bowman's capsule epithelium was diagnosed. Multiple yellowish‒white nodules (1-3 cm) were found in the liver and diagnosed as neuroendocrine carcinoma with metastases to the lungs, adrenal glands and pancreaticoduodenal lymph nodes.

Three new species of Eimeria (Apicomplexa: Eimeriidae) from the Amami rabbit, Pentalagus furnessi (Mammalia: Leporidae).

The Amami rabbit, Pentalagus furnessi (Mammalia: Lagomorpha: Leporidae), is a relict and endangered species endemic to the Amami-Oshima and Tokunoshima Islands, located in southwestern Japan. Here, we described three new species of Eimeria (Apicomplexa: Eimeriidae) parasites detected from fecal samples of wild Amami rabbits. Eimeria furnessi n. sp., recorded in 21 (58.3%) samples, has ellipsoidal oocysts with two walls and micropyle, 26.0 × 16.6 µm, and elongate-ovoidal sporocysts, 13.1 × 6.3 µm, with Stieda body. Eimeria hilleri n. sp., recorded in 9 (25.0%) samples, has ellipsoidal oocysts with two walls and micropyle, 34.7 × 21.4 µm, and elongate-fusiform to elongate-ovoidal sporocysts, 15.7 × 8.3 µm, with Stieda and substieda bodies. Eimeria sagentae n. sp., recorded in 13 (36.1%) samples, has ellipsoidal oocysts with two walls and micropyle, 20.9 × 14.5 µm, and elongate-ovoidal sporocysts, 10.4 × 5.0 µm, with Stieda body. The three new species can be distinguished by the size and color of their oocysts. Further studies related to the pathogenicity of these parasites can improve the breeding and propagation procedures of the Amami rabbit.

Gp130-Mediated STAT3 Activation Contributes to the Aggressiveness of Pancreatic Cancer through H19 Long Non-Coding RNA Expression.

Signaling pathways involving signal transducer and activator of transcription 3 (STAT3) play key roles in the aggressiveness of pancreatic ductal adenocarcinoma (PDAC), including their tumorigenesis, invasion, and metastasis. Cancer stem cells (CSCs) have been correlated with PDAC aggressiveness, and activation of STAT3 is involved in the regulation of CSC properties. Here, we investigated the involvement of interleukin-6 (IL-6) or the leukemia inhibitory factor (LIF)/glycoprotein 130 (gp130)/STAT3 pathway and their role in pancreatic CSCs. In PDAC CSC-like cells formed by culturing on a low attachment plate, autocrine/paracrine IL-6 or LIF contributes to gp130/STAT3 pathway activation. Using a gp130 inhibitor, we determined that the gp130/STAT3 pathway contributes to the maintenance of stemness features, the expression of membrane-type 1 matrix metalloproteinase (MT1-MMP), and the invasion of PDAC CSC-like cells. The gp130/STAT3 pathway also modulates the transforming growth factor (TGF)-ß1/Smad pathway required for epithelial-mesenchymal transition induction through regulation of TGFß-RII expression in PDAC CSC-like cells. Furthermore, chromatin immunoprecipitation assays revealed that p-STAT3 can access the active promoter region of H19 to influence this metastasis-related long non-coding RNA and contribute to its transcription in PDAC CSC-like cells. Therefore, the autocrine/paracrine IL-6 or LIF/gp130/STAT3 pathway in PDAC CSC-like cells may eventually facilitate invasion and metastasis, two hallmarks of malignancy. We propose that inhibition of the gp130/STAT3 pathway provides a promising strategy for targeting CSCs for the treatment of PDAC.

Involvement of Nestin in the Progression of Canine Mammary Carcinoma.

Nestin, a class VI intermediate filament protein, is known to be expressed in various types of human neoplasms, including breast cancer, and is associated with their progression. However, its expression and role in canine mammary tumors remain unknown. We analyzed nestin expression in canine mammary tumors using in situ hybridization and immunohistochemistry. We also investigated its role in a canine mammary carcinoma cell line using RNA interference. Nestin expression was not observed in luminal epithelial cells of any of the 62 cases of benign mammary lesions examined, although myoepithelial cells showed its expression in most cases. In 16/50 (32%) primary mammary carcinomas and 6/15 (40%) metastases of mammary carcinomas, cytoplasmic nestin expression was detected in luminal epithelial cells. In luminal cells of primary mammary carcinomas, its expression was positively related to several pathological parameters that indicate high-grade malignancy, including histological grading (P < .01), vascular/lymphatic invasion (P < .01), Ki-67 index (P < .01), and metastasis (P < .05). Immunohistochemistry revealed that nestin expression was related to vimentin expression in mammary carcinomas (P < .01). This relationship was confirmed using reverse transcription-quantitative polymerase chain reaction using 9 cell lines derived from canine mammary carcinoma (P < .01). Finally, nestin knockdown in canine mammary carcinoma cells using small interfering RNA inhibited cell proliferation and migration based on WST-8, Boyden chamber, and cell-tracking assays. These findings suggest that nestin may at least partially mediate these behaviors of canine mammary carcinoma cells.

Genomic characterisation of bovine papillomavirus types 1 and 2 identified in equine sarcoids in Japan.

BACKGROUND: Bovine papillomavirus types 1 and 2 (BPV1/2) infection in horses has been associated with the development of equine sarcoids. Previous findings revealed the presence of sarcoid-associated BPV sequence variants that have been proposed as a key factor of cross-species infection in horses. To verify this hypothesis, sarcoid-associated BPV variants should be identified regardless of geographic location. OBJECTIVES: Sequence analyses of BPV1/2 derived from both horses and cattle were conducted to clarify the sarcoid-associated sequence variants. The aim of this study was to clarify the correlation between BPV phylogeny and the geographic origin/host species. STUDY DESIGN: Cross-sectional study. METHODS: Conventional PCR to detect BPV1/2 was performed with genomic DNA extracted from equine sarcoid (n = 10) and bovine papilloma (n = 10) samples collected in Japan. Direct sequencing results were compared between equine and bovine (equine/bovine)-derived BPV to identify sarcoid-associated variants of two early regions (E2, E5), one late region (L1) and the long control region (LCR). Phylogenetic and phylogeny-trait correlation were analysed using Bayesian Markov chain Monte Carlo (MCMC) method and Bayesian tip-association significance testing (BaTS). RESULTS: Seven BPV1 and three BPV2 were identified from equine sarcoids using PCR and direct sequencing. Sequence analysis of equine/bovine-derived samples showed no sarcoid-associated variants in four regions (E2, E5, L1 and LCR) of either BPV1 or BPV2. The phylogenetic tree of BPV1 E2, L1 and LCR tended to cluster within its geographic origins. BaTS analysis demonstrated that BPV1 sequence variability may be due to the geographic origin rather than host species difference. MAIN LIMITATIONS: There was a limitation in sample numbers. CONCLUSIONS: This study supports the geographic-specific hypothesis of sequence variability, suggesting that BPV1 is shared between local equids and bovids. However, more extensively collected sequences worldwide and functional evaluations are needed to verify the geographic-specific sequence variability of BPV1/2 between equine- and bovine-derived sequence.

FGFR4 Inhibitor BLU9931 Attenuates Pancreatic Cancer Cell Proliferation and Invasion While Inducing Senescence: Evidence for Senolytic Therapy Potential in Pancreatic Cancer.

Fibroblast growth factor receptor 4 (FGFR4), one of four tyrosine kinase receptors for FGFs, is involved in diverse cellular processes. Activation of FGF19/FGFR4 signaling is closely associated with cancer development and progression. In this study, we examined the expression and roles of FGF19/FGFR4 signaling in human pancreatic ductal adenocarcinoma (PDAC). In human PDAC cases, FGFR4 expression positively correlated with larger primary tumors and more advanced stages. Among eight PDAC cell lines, FGFR4 was expressed at the highest levels in PK-1 cells, in which single-nucleotide polymorphism G388R in FGFR4 was detected. For inhibition of autocrine/paracrine FGF19/FGFR4 signaling, we used BLU9931, a highly selective FGFR4 inhibitor. Inhibition of signal transduction through ERK, AKT, and STAT3 pathways by BLU9931 reduced proliferation in FGF19/FGFR4 signaling-activated PDAC cells. By contrast, BLU9931 did not alter stemness features, including stemness marker expression, anticancer drug resistance, and sphere-forming ability. However, BLU9931 inhibited cell invasion, in part, by downregulating membrane-type matrix metalloproteinase-1 in FGF19/FGFR4 signaling-activated PDAC cells. Furthermore, downregulation of SIRT1 and SIRT6 by BLU9931 contributed to senescence induction, priming these cells for quercetin-induced death, a process termed senolysis. Thus, we propose that BLU9931 is a promising therapeutic agent in FGFR4-positive PDAC, especially when combined with senolysis (195/200).

Hepatic neuroendocrine carcinoma with metastases to the lymph nodes in a sika deer (Cervus nippon yakushimae).

A 26-year and 6-month-old male sika deer that was kept at the Showa Park, Tokyo, Japan, collapsed and died of severe disease wasting and severe tabefaction. Grossly, numerous masses, 0.3-1.0 cm diameter, were dispersed throughout the liver. The multiple masses were composed of tumor cells, which had hypochromatic nuclei and abundant faintly eosinophilic cytoplasm, arranged in nests of various sizes. Immunohistochemically, tumor cells were positive for cytokeratin, chromogranin A, synaptophysin and gastrin. Ultrastructurally, the cytoplasm of the tumor cells contained abundant membrane-bound electron-dense granules. A metastatic lesion was observed in the renal, hepatic and pancreatic lymph nodes. On the basis of these findings, this tumor was diagnosed as a neuroendocrine carcinoma with metastases to the lymph nodes.

Alien parasitic infections in the endangered Ryukyu long-furred rat (Diplothrix legata) on Amami-Oshima Island, Japan.

There is limited knowledge about parasites of the endangered Ryukyu long-furred rat, Diplothrix legata (Murinae, Rodentia) endemic to Okinawa, Tokunoshima, and Amami-Oshima Islands in Japan. In the present study, postmortem histopathological examination of an individual found on Amami-Oshima Island revealed a mixed helminth infection of Calodium hepaticum, Hydatigera taeniaeformis, and Angiostrongylus cantonensis. These helminths are considered non-native to Amami-Oshima Island and are maintained by invasive mammals, such as non-native rats and outdoor cats. This observation presents a new host record for C. hepaticum and H. taeniaeformis and the first record of A. cantonensis in Ryukyu long-furred rat on Amami-Oshima Island.

Enhanced morphological and functional differences of pancreatic cancer with epithelial or mesenchymal characteristics in 3D culture.

Pancreatic cancer, composed of heterogeneous cancer cells, alters epithelial to mesenchymal features during growth and metastasis. In this study, we aimed to characterize pancreatic ductal adenocarcinoma (PDAC) cells showing epithelial or mesenchymal features in 3D culture. In 3D culture, PK-1 cells had high E-cadherin and low vimentin expression and exhibited a round-like appearance encircled by flat cells. PANC-1 cells had high vimentin and low E-cadherin expression and formed grape-like spheres. PK-1 cells had secretary granules and many microvilli, desmosomes, and adherens junctions, while PANC-1 cells had few microvilli, adherens junction, and no desmosomes. Cytokeratin 7, trypsin, CA19-9, and E-cadherin were highly expressed in PK-1 cells but not in PANC-1 cells. Ki-67 was diffusely expressed in PANC-1 spheres but was restricted to the peripheral flat cells of PK-1 spheres. PANC-1 and PK-1 cells were positive for transforming growth factor (TGF) ß receptor II and phosphorylated smad2/3, but PK-1 cells were smad4 negative. Taken together, 3D culture enhanced morphofunctional differences of PDAC cells showing epithelial or mesenchymal characteristics, and epithelial phenotype maintenance may be due to the ineffectiveness of the TGF- ß pathway. Clarification of heterogeneity using 3D culture may be useful for development of individualized diagnostic and therapeutic methods in patients with PDAC.

Toxoplasma gondii infection in Amami spiny rat on Amami-Oshima Island, Japan.

The Amami spiny rat (Tokudaia osimensis) is an endangered rodent species that is endemic to the forests of Amami-Oshima Island, Kagoshima, Japan. In July 2018, a deceased adult male Amami spiny rat was found on the Yuwandake Mountain Trail on the south-central coast of Amami-Oshima Island. Histopathological observations revealed protozoan infections in the liver, lungs, and heart. Nested or semi-nested PCRs targeting the B1, SAG3, GRA6, and ROP18 genes successfully detected the genomic DNA of Toxoplasma gondii in the formalin-fixed and paraffin-embedded specimen. Sequence analyses of the SAG3, GRA6, and ROP18 genes suggested that the strain detected in the study specimen was related to the type II strain of T. gondii. This is the first confirmed case of T. gondii infection in an Amami spiny rat.

Malignant rhabdoid tumor of the musk gland and systemic T-cell lymphoma in a masked palm civet (Paguma larvata).

A 21-year-old male masked palm civet died after 2 months of continuous abdominal distention and poor appetite. Grossly, both musk glands were markedly swelled. Microscopically, round, polygonal and spindle neoplastic cells proliferated diffusely in the right musk gland and a metastatic focus was observed in the lung. The neoplastic cells had abundant cytoplasm with faintly eosinophilic inclusions that ultrastructurally corresponded to whorl aggregates of intermediate filaments. Immunohistochemically, these cells were positive for vimentin, cytokeratins and glial fibrillary acidic protein and negative for desmin. Based on these findings, the tumor was diagnosed as malignant rhabdoid tumor. Papillary adenoma was seen in the opposite musk gland. T-cell lymphoma of the lymph nodes, small intestine and liver was considered as the cause of death.

Expression and Roles of S100A4 in Anaplastic Cells of Canine Mammary Carcinomas.

S100A4 (metastasin), a member of the S100 protein family, was initially identified in metastatic cells and is well established as a marker of aggressive human cancer. However, expression and roles of S100A4 in canine mammary tumors have not been clarified. In this study, expression of S100A4 was examined immunohistochemically in normal, hyperplastic, and neoplastic mammary glands of dogs. In all normal and benign lesions, S100A4 was restricted to a few stromal fibroblasts and inflammatory cells. However, in 7 of 57 (12%) of the malignant tumors examined, cytoplasmic and nuclear expression of S100A4 was observed in epithelial tumor cells and stromal cells. Particularly, the frequency of S100A4-positive anaplastic carcinomas was high (4/8 cases, 50%). Next, we established a novel cell line, named NV-CML, from a S100A4-positive canine mammary carcinoma. The cultured NV-CML cells and the tumors that developed in the immunodeficient mice after subcutaneous injection of the cells maintained the immunophenotype of the original tumor, including S100A4 expression. Using this cell line, we examined the cellular functions of S100A4 using RNA interference. S100A4 expression level in NV-CML cells transfected with small interfering RNA (siRNA) targeting canine S100A4 (siS100A4) was reduced to about one-fifth of those with negative-control siRNA (siNeg). Cell proliferation in WST-8 assay and cell migration in Boyden chamber assay were significantly decreased in siS100A4-transfected cells compared with siNeg-transfected cells. These findings suggest that S100A4 may be related to progression of canine mammary carcinomas via its influence on cell growth and motility.

H19 long non-coding RNA contributes to sphere formation and invasion through regulation of CD24 and integrin expression in pancreatic cancer cells.

The long non-coding RNA H19 is highly expressed in several cancers, and the functions of H19 vary among cancer cell types. Recently, we reported that H19 contributes to the metastasis of pancreatic ductal adenocarcinoma (PDAC) cells and that inhibition of H19 reduces metastasis in vivo. However, the molecular mechanisms underlying the metastasis-promoting role of H19 in PDAC cells remain poorly elucidated. In this study, we clarified the mechanisms by which H19 regulates PDAC metastasis, with a focus on cancer stem cells (CSCs), by using H19-overexpressing and knockdown PDAC cells. Whereas the sphere-formation and invasion abilities of PDAC cells depended on H19 expression levels, other CSC characteristics of the cells, including stemness-marker expression and anticancer-drug resistance, were unaffected by H19 levels. Furthermore, metalloproteinase activity, a key mediator of invasion, was also independent of H19 expression. By contrast, H19 promoted cell adhesion through regulation of integrin and CD24 expression. Notably, the increased adhesion of H19-overexpressing cells was blocked by an anti-ß1-integrin antibody, and this resulted in the inhibition of sphere formation and invasion. Thus, H19 plays critical roles in the CSC self-renewal and cell adhesion of PDAC that lead to invasion and metastasis. Our findings suggest that H19 represents a novel therapeutic target for the metastasis of pancreatic cancer.

Pancreatic cancer stem cells: features and detection methods.

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy with a high incidence of distant metastasis and recurrence. Cancer stem cells (CSCs), which are pluripotent, self-renewable, and capable of forming tumors, contribute to PDAC initiation and metastasis and are responsible for resistance to chemotherapy and radiation. Three types of experimental methods are commonly used to identify CSCs: CSC-specific marker detection, a sphere-formation assay that reveals cell proliferation under non-adherent conditions, and detection of side-population (SP) cells that possess high intracellular-to-extracellular pump functions. Several CSC-specific markers have been reported in PDACs, including CD133, CD24, CD44, CXCR4, EpCAM, ABCG2, c-Met, ALDH-1, and nestin. There remains controversy regarding which markers are specific to PDAC CSCs and which are expressed alone or in combination in CSCs. Examining characteristics of isolated CSCs and discovering CSC-specific treatment options are important to improve the prognosis of PDAC cases. This review summarizes CSC-detection methods for PDAC, including CSC-marker detection, the sphere-formation assay, and detection of SP cells.

Reduced expression of the H19 long non-coding RNA inhibits pancreatic cancer metastasis.

H19 is an oncofetal RNA expressed in the developing embryo as well as in bladder, breast, gastric, pancreatic, hepatocellular, and prostate cancers. Recent studies have shown that H19 enhances cancer invasion and metastasis; however, its roles in cancer remain controversial. In the current study, H19 exhibited the second largest increase (82.4-fold) and represented the only non-protein coding gene among 11 genes identified that were elevated over 10-fold in lung-metastasis-derived pancreatic cancer cells compared with their parental cells using a mouse metastatic model. Subsequently, we further clarified the roles of H19 in pancreatic cancer growth and metastasis using in vitro and in vivo techniques. In situ hybridization showed that H19 was detected in 23 of 139 invasive ductal carcinomas (17%), and that H19 expression positively correlated with higher histological grades (P < 0.0001). Overexpression of H19 in PANC-1 pancreatic cancer cells induced higher motilities, whereas H19 inhibition using shRNA and siRNA showed opposite results; however, cell growth rates were not impacted. Intravenous injection of H19 shRNA vector-transfected PANC-1 cells yielded marked inhibition of metastasis in the liver and lungs of immunodeficient mice. These findings suggest that H19 has important roles in pancreatic cancer metastasis, and that inhibition of H19 represents a novel candidate for pancreatic cancer therapy.

Expression and role of long non-coding RNA H19 in carcinogenesis.

With the recent advent of whole genome and transcriptome sequencing technologies, long non-coding RNAs have been brought into the spotlight in molecular biology. H19 was one of the first reported long non-coding RNAs; its expression is high in embryonic organs and absent or greatly reduced in most adult tissues. Accumulating evidence suggests that H19 plays crucial roles in embryogenesis. However, its levels are increased in different cancers, including breast, hepato-gastrointestinal, urological, respiratory, and brain tumors. Although there have been several controversial reports as to whether H19 is oncogenic or tumor-suppressive, most studies have indicated that H19 is associated with growth, migration, invasion, and/or metastasis in many cancers; however, its reported functional mechanisms vary among cancer types. Furthermore, serum H19 levels in patients with certain cancers have been suggested to be useful for diagnosis and prognosis. Thus, H19 long non-coding RNA might be a candidate for development of promising therapeutic and diagnostic modalities for several cancers. The purpose of this review is to provide an inclusive report on the functional role of H19 in different cancers.