Fibrosarcomatous Transformation in Dermatofibrosarcoma Protuberans of the Male Breast and its Association with Magnetic Resonance Imaging and Immunohistopathologic Features.

BACKGROUND: Dermatofibrosarcoma Protuberans (DFSP) is a rare soft tissue sarcoma, accounting for approximately 1% of all tumors; however, DFSP of the breast is extremely rare. Moreover, DFSP generally has a low malignant potential and is characterized by a high rate of local recurrence along with a small but definite risk of metastasis. The risk of metastasis is higher in fibrosarcomatous transformation in DFSP than in ordinary DFSP. CASE REPORT: We have, herein, reported a case of a 61-year-old male patient with fibrosarcomatous transformation in DFSP. Preoperative Dynamic Contrastenhanced Magnetic Resonance Imaging (DCE-MRI) of the breast revealed an oval-shaped mass with heterogeneous internal enhancement, a large vessel embedded within, and a washout curve pattern on kinetic curve analysis. The mass exhibited a hyperintense signal on Diffusion-weighted Imaging (DWI), with a low apparent diffusion coefficient value. Histologically, the bland spindle tumor cells were arranged in a storiform pattern. Areas with the highest histological grade demonstrated increased cellularity, cytological atypia, and mitotic activity. Immunohistochemically, Ki-67 and p53 were highly expressed. CONCLUSION: Recognizing the risk and accurately diagnosing fibrosarcomatous transformation in male breast DFSP are critical for improving prognosis and establishing appropriate treatment and follow-up plans. This emphasizes the significance of combining immunohistopathological features with DCE-MRI and DWI to assist clinicians in the early and accurate diagnosis of sarcomas arising from male breast DFSP.

SIRT1 ISGylation accelerates tumor progression by unleashing SIRT1 from the inactive state to promote its deacetylase activity.

ISG15 is an interferon-stimulated ubiquitin-like protein (UBL) with multifaceted roles as a posttranslational modifier in ISG15 conjugation (ISGylation). However, the mechanistic consequences of ISGylation in cancer have not been fully elucidated, largely due to a lack of knowledge on the ISG15 target repertoire. Here, we identified SIRT1, a nicotinamide adenine dinucleotide (NAD+)-dependent protein deacetylase, as a new target for ISGylation. SIRT1 ISGylation impairs the association of SIRT1 with its negative regulator, deleted in breast cancer 1 (DBC1), which unleashes SIRT1 from its inactive state and leads to an increase in its deacetylase activity. Importantly, SIRT1 ISGylation promoted lung cancer progression and limited lung cancer cell sensitivity to DNA damage-based therapeutics in vivo and in vitro models. The levels of ISG15 mRNA and protein were significantly higher in lung cancer tissues than in adjacent normal tissues. Accordingly, elevated expression of SIRT1 and ISG15 was associated with poor prognosis in lung cancer patients, a finding that could be translated for lung cancer patient stratification and disease outcome evaluation. Taken together, our findings provide a mechanistic understanding of the regulatory effect of SIRT1 ISGylation on tumor progression and therapeutic efficacy in lung cancer.

FAM83H Expression Is Associated with Tumor-Infiltrating PD1-Positive Lymphocytes and Predicts the Survival of Breast Carcinoma Patients.

BACKGROUND: FAM83H has been implicated in cancer progression, and PD1 is an important target for anti-cancer immune checkpoint therapy. Recent studies suggest an association between FAM83H expression and immune infiltration. However, studies on the roles of FAM83H and its relationship with PD1 in breast carcinomas have been limited. METHODS: Immunohistochemical expression of FAM83H and PD1 and their prognostic significance were evaluated in 198 breast carcinomas. RESULTS: The expression of FAM83H in cancer cells was significantly associated with the presence of PD1-positive lymphoid cells within breast carcinoma tissue. Individual and co-expression patterns of nuclear FAM83H and PD1 were significantly associated with shorter survival of breast carcinomas in univariate analysis. In multivariate analysis, the expression of nuclear FAM83H (overall survival, p < 0.001; relapse-free survival, p = 0.003), PD1 (overall survival, p < 0.001; relapse-free survival, p = 0.003), and co-expression patterns of nuclear FAM83H and PD1 (overall survival, p < 0.001; relapse-free survival, p < 0.001) were the independent indicators of overall survival and relapse-free survival of breast carcinoma patients. CONCLUSIONS: This study suggests a close association between FAM83H expression and the infiltration of PD1-positive lymphoid cells in breast carcinomas and their expression as the prognostic indicators for breast carcinoma patients, and further studies are needed to clarify this relationship.

Graft lymphoma in a kidney transplant recipient: a case report.

Posttransplant lymphoproliferative disorders (PTLDs) are severe complications with heterogeneous clinical pictures involving abnormal lymphoproliferation in solid organ transplants and are known to be closely associated with Epstein-Barr virus (EBV) infection. Herein, we present a case of graft lymphoma in a febrile kidney transplant recipient. A 37-year-old woman was admitted with an abrupt 39 °C fever, mild graft discomfort, and gross hematuria. She had received deceased donor kidney transplantation 8 years earlier, but developed graft failure due to a recurrence of immunoglobulin A nephropathy. Laboratory tests revealed anemia and elevated levels of inflammatory markers. Enhanced abdominopelvic computed tomography showed graft swelling with perirenal fat stranding. Thus, we administered antibiotics for a urinary tract infection and increased the doses of steroids due to suspicion of graft intolerance syndrome. However, the patient's symptoms gradually worsened. Eventually, we performed graft nephrectomy and histologically confirmed EBV-positive diffuse large B cell lymphoma. We report a case in which a PTLD was considered in the differential diagnosis of a kidney transplant recipient with symptoms similar to those of a urinary tract infection or graft intolerance syndrome.

Acute myelomonocytic leukemia and T-lymphoblastic lymphoma as simultaneous bilineage hematologic malignancy treated with decitabine: A case report.

BACKGROUND: Simultaneous bilineage hematologic malignancies are rare; however, several cases of acute myeloid leukemia (AML) and T-lymphoblastic lymphoma (T-LBL) co-occurrence have been reported. A standard treatment for simultaneous AML and T-LBL has not yet been established, and its prognosis is very poor. Further studies to develop standard treatments are required to increase patient survival rates. CASE SUMMARY: A 69-year-old man complaining of pleuritic chest pain visited the emergency room. Computed tomography revealed multiple enlarged lymph nodes (LNs) in the neck and groin and pulmonary thromboembolism with pulmonary infarction. Furthermore, a peripheral blood smear performed due to leukocytosis revealed circulating blasts. Acute myelomonocytic leukemia (AMML) was diagnosed after bone marrow examination, and T-LBL positivity for terminal deoxynucleotidyl transferase, cluster of differentiation (CD)34, and CD4 was confirmed by cervical LN biopsy. Decitabine and dexamethasone were administered because he could not receive intensive chemotherapy due to poor performance status. Complete remission of AMML and T-LBL was achieved after 4 cycles of decitabine plus dexamethasone. CONCLUSION: We report the therapeutic effect of decitabine, a hypomethylating agent (HMA), in patients with concurrent bilineage hematologic malignancies and suggest that further studies are required to evaluate the therapeutic effect of HMAs on both lymphoid and bilineage hematologic malignancies.

Sirtuin 6 Overexpression Improves Rotator Cuff Tendon-to-Bone Healing in the Aged.

Aging is an independent risk factor for recurrent tearing after surgical repair of rotator cuff ruptures around the tendon-to-bone area. However, aging signature factors and related mechanisms involved in the healing of the rotator cuff are still unknown. We hypothesized that differences in proteins involved in the rotator cuff according to age may affect tendon-to-bone healing. The proteome analysis performed to identify the signature aging proteins of the rotator cuff confirmed the sirtuin signal as an age-specific protein. In particular, the expression of SIRT6 was markedly down-regulated with age. Ingenuity pathway analysis of omics data from age-dependent rat rotator cuffs and linear regression from human rotator cuffs showed SIRT6 to be closely related to the Wnt/ß-catenin signal. We confirmed that overexpression of SIRT6 in the rotator cuff and primary tenocyte regulated canonical Wnt signaling by inhibiting the transcriptional expression of sclerostin, a Wnt antagonist. Finally, SIRT6 overexpression promoted tendon-to-bone healing after tenotomy with reconstruction in elderly rats. This approach is considered an effective treatment method for recovery from recurrent rotator cuff tears, which frequently occur in the elderly.

p21-activated kinase 4 suppresses fatty acid ß-oxidation and ketogenesis by phosphorylating NCoR1.

PPARα corepressor NCoR1 is a key regulator of fatty acid ß-oxidation and ketogenesis. However, its regulatory mechanism is largely unknown. Here, we report that oncoprotein p21-activated kinase 4 (PAK4) is an NCoR1 kinase. Specifically, PAK4 phosphorylates NCoR1 at T1619/T2124, resulting in an increase in its nuclear localization and interaction with PPARα, thereby repressing the transcriptional activity of PPARα. We observe impaired ketogenesis and increases in PAK4 protein and NCoR1 phosphorylation levels in liver tissues of high fat diet-fed mice, NAFLD patients, and hepatocellular carcinoma patients. Forced overexpression of PAK4 in mice represses ketogenesis and thereby increases hepatic fat accumulation, whereas genetic ablation or pharmacological inhibition of PAK4 exhibites an opposite phenotype. Interestingly, PAK4 protein levels are significantly suppressed by fasting, largely through either cAMP/PKA- or Sirt1-mediated ubiquitination and proteasome degradation. In this way, our findings provide evidence for a PAK4-NCoR1/PPARα signaling pathway that regulates fatty acid ß-oxidation and ketogenesis.

Treatment of malignant perivascular epithelioid cell tumor (PEComa) on the knee with an anterolateral thigh free flap: A case report.

RATIONALE: The World Health Organization defines a perivascular epithelioid cell tumor (PEComa) as a mesenchymal neoplasia composed of perivascular epithelioid cells with characteristic morphological and immunohistochemical features. Although PEComas have the potential to behave in a malignant fashion, malignant PEComas are extremely rare. PATIENT CONCERNS: An 83-year-old man visited our clinic presented with palpable, painless, and movable mass in the right knee area. DIAGNOSES: Malignant PEComa was diagnosed by incisional biopsy. No metastases was confirmed by radiologic imaging including PET/CT, magnetic resonance imaging, high resolution computed tomography. INTERVENTIONS: We performed wide excision of the mass and used an anterolateral thigh free flap to reconstruct the defect on the right knee. OUTCOMES: The permanent histopathology showed malignant PEComa was totally resected. The flap which was performed to cover the defect was survived and the patient discharge without any complications. LESSONS: PEComa can metastasize to various anatomical regions. Although there is no established standardized treatment, radical resection is still considered the cornerstone of treatment. Rapid and appropriate defect coverage is important to improve the patient's prognosis.

Expression Patterns of PAK4 and PHF8 Are Associated with the Survival of Gallbladder Carcinoma Patients.

BACKGROUND: PAK4 and PHF8 are involved in cancer progression and are under evaluation as targets for cancer therapy. However, despite extensive studies in human cancers, there are limited reports on the roles of PAK4 and PHF8 in gallbladder cancers. METHODS: Immunohistochemical expression of PAK4 and PHF8 and their prognostic significance were evaluated in 148 human gallbladder carcinomas. RESULTS: PAK4 expression was significantly associated with PHF8 expression in gallbladder carcinomas. Positive expression of nuclear PAK4, cytoplasmic PAK4, nuclear PHF8, and cytoplasmic PHF8 were significantly associated with shorter overall survival and relapse-free survival in univariate analysis. Multivariate analysis showed that nuclear PAK4 expression and nuclear PHF8 expression were independent predictors of overall survival and relapse-free survival in gallbladder carcinomas. Furthermore, coexpression of nuclear PAK4 and nuclear PHF8 predicted shorter overall survival (p < 0.001) and relapse-free survival (p < 0.001) of gallbladder carcinoma in multivariate analysis. CONCLUSIONS: This study suggests that the individual and coexpression patterns of PAK4 and PHF8 as the prognostic indicators for gallbladder carcinoma patients.

Clinical significance of p53 protein expression and TP53 variation status in colorectal cancer.

In human colorectal cancer (CRC), TP53 is one of the most important driver genes. Immunohistochemistry (IHC) has been used most often to assess the variational status of TP53. Recently, next-generation sequencing (NGS) of the TP53 gene has increased. However, to our knowledge, a comparison between TP53 status evaluated by IHC and NGS has not been studied. Therefore, the primary aim of this study was to compare the clinical effect of TP53 status evaluated by IHC and NGS in patients with CRC. The secondary aim was to investigate the correlation between expression of p53 by IHC and variational status of TP53 by NGS. We performed immunohistochemical staining of p53 and sequencing of TP53 by NGS in 204 human samples of CRC. We then analyzed the correlation between variational status of TP53 and p53 expression, along with their prognostic impact in CRC patients. There was significant correlation between p53 expression and TP53 variation, TP53 variation and higher N stage, and positive p53 expression and higher N stage. Positive IHC expression of p53 was significantly associated with overall survival (OS) of CRC patients by univariate analysis and was revealed as an independent prognostic factor by multivariate analysis. Additionally, the nonsense/frameshift p53 expression pattern showed a significantly better prognosis than the wild type and missense p53 expression patterns. However, the variational status of TP53 was not significant in OS of CRC patients. These results suggest that IHC expression of p53 protein correlates with variation status of TP53 and expression of p53 protein rather than variation status of TP53 has more significant impact on the OS of CRC patients.

Individual and Co-Expression Patterns of FAM83H and SCRIB at Diagnosis Are Associated with the Survival of Colorectal Carcinoma Patients.

Background: FAM83H is important in teeth development; however, an increasing number of reports have indicated a role for it in human cancers. FAM83H is involved in cancer progression in association with various oncogenic molecules, including SCRIB. In the analysis of the public database, there was a significant association between FAM83H and SCRIB in colorectal carcinomas. However, studies evaluating the association of FAM83H and SCRIB in colorectal carcinoma have been limited. Methods: The clinicopathological significance of the immunohistochemical expression of FAM83H and SCRIB was evaluated in 222 colorectal carcinomas. Results: The expressions of FAM83H and SCRIB were significantly associated in colorectal carcinoma tissue. In univariate analysis, the nuclear expressions of FAM83H and SCRIB and the cytoplasmic expression of SCRIB were significantly associated with shorter survival of colorectal carcinomas. The nuclear expressions of FAM83H and SCRIB and the cytoplasmic expression of SCRIB were independent indicators of shorter cancer-specific survival in multivariate analysis. A co-expression pattern of nuclear FAM83H and cytoplasmic SCRIB predicted shorter cancer-specific survival (p < 0.001) and relapse-free survival (p = 0.032) in multivariate analysis. Conclusions: This study suggests that FAM83H and SCRIB might be used as prognostic markers of colorectal carcinomas and as potential therapeutic targets for colorectal carcinomas.

An in vitro study on anti-carcinogenic effect of remdesivir in human ovarian cancer cells via generation of reactive oxygen species.

BACKGROUND: Remdesivir is an anti-viral drug that inhibits RNA polymerase. In 2020, remdesivir was recognized as the most promising therapeutic agents against coronavirus disease 2019 (COVID-19). However, the effects of remdesivir on cancers have hardly been studied. PURPOSE: Here, we reported that the anti-carcinogenic effect of remdesivir on SKOV3 cells, one of human ovarian cancer cell lines. RESEARCH DESIGN: We anlalyzed the anti-carcarcinogenic effect of remdesivir in SKOV3 cells by performing in vitro cell assay and western blotting. RESULTS: WST-1 showed that remdesivir decreased cell viability in SKOV3 cells. Experiments conducted by Muse Cell Analyzer showed that remdesivir-induced apoptosis in SKOV3 cells. We found that the expression level of FOXO3, Bax, and Bim increased, whereas Bcl-2, caspase-3, and caspase-7 decreased by remdesivir in SKOV3 cells. Furthermore, we observed that intracellular reactive oxygen species (ROS) level increased after treatment of remdesivir in SKOV3 cells. Interestingly, cytotoxicity of remdesivir decreased after treatment of N-Acetylcysteine. CONCLUSION: Taken together, our results demonstrated that remdesivir has an anti-carcinogenic effect on SKOV3 cells vis up-regulation of reactive oxygen species, which suggests that remdesivir could be a promising reagent for treatment of ovarian cancer.

Acetylshikonin, A Novel CYP2J2 Inhibitor, Induces Apoptosis in RCC Cells via FOXO3 Activation and ROS Elevation.

Acetylshikonin is a shikonin derivative originated from Lithospermum erythrorhizon roots that exhibits various biological activities, including granulation tissue formation, promotion of inflammatory effects, and inhibition of angiogenesis. The anticancer effect of acetylshikonin was also investigated in several cancer cells; however, the effect against renal cell carcinoma (RCC) have not yet been studied. In this study, we aimed to investigate the anticarcinogenic mechanism of acetylshikonin in A498 and ACHN, human RCC cell lines. MTT (3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide), cell counting, and colony forming assay showed that acetylshikonin induced cytotoxic and antiproliferative effects in a dose- and time-dependent manner. Cell cycle analysis and annexin V/propidium iodide (PI) double staining assay indicated the increase of subG1 phase and apoptotic rates. Also, DNA fragmentation was observed by using the TUNEL and comet assays. The intracellular ROS level in acetylshikonin-treated RCC was evaluated using DCF-DA. The ROS level was increased and cell viability was decreased in a dose- and time-dependent manner, while those were recovered when cotreated with NAC. Western blotting analysis showed that acetylshikonin treatment increased the expression of FOXO3, cleaved PARP, cleaved caspase-3, -6, -7, -8, -9, γH2AX, Bim, Bax, p21, and p27 while decreased the expressions of CYP2J2, peroxiredoxin, and thioredoxin-1, Bcl-2, and Bcl-xL. Simultaneously, nuclear translocation of FOXO3 and p27 was observed in cytoplasmic and nuclear fractionated western blot analysis. Acetylshikonin was formerly identified as a novel inhibitor of CYP2J2 protein in our previous study and it was evaluated that CYP2J2 was downregulated in acetylshikonin-treated RCC. CYP2J2 siRNA transfection augmented that apoptotic effect of acetylshikonin in A498 and ACHN via up-regulation of FOXO3 expression. In conclusion, we showed that the apoptotic potential of acetylshikonin against RCC is mediated via increase of intracellular ROS level, activation of FOXO3, and inhibition of CYP2J2 expressions. This study offers that acetylshikonin may be a considerable alternative therapeutic option for RCC treatment by targeting FOXO3 and CYP2J2.

IL4Rα and IL13Rα1 Are Involved in the Development of Human Gallbladder Cancer.

BACKGROUND: Gallbladder cancer is commonly associated with inflammation, which indicates that inflammation-related cytokines and cytokine receptors are related to the progression of gallbladder cancers. Interleukin 4 (IL4) is a well-known cytokine that promotes the differentiation of naive helper T cells (Th0) to T helper type 2 cells (Th2). IL13 is a cytokine that is secreted by Th2 cells. IL4 and IL13 are closely related in immune responses. However, the role of IL4Rα and IL13Rα1 signaling pathway has not been fully understood in the development of gallbladder cancer. METHODS: In human gallbladder carcinomas, the expression of IL4Rα and IL13Rα1 were evaluated with immunohistochemical staining in tissue microarray tissue sections. After knockdown of IL4Rα or IL13Rα1, cell assays to measure the proliferation and apoptosis and Western blotting analysis were conducted in SNU308 human gallbladder cancer cells. Since Janus kinases2 (JAK2) was considered as one of the down-stream kinases under IL4Rα and IL13Rα1 complex, the same kinds of experiments were performed in SNU308 cells treated with AZD1480, Janus-associated kinases2 (JAK2) inhibitor, to demonstrate the cytotoxic effect of AZD1480 in SNU308 cells. RESULTS: Immunohistochemical expression of IL4Rα was significantly associated with the expression of IL13Rα1 in human carcinoma tissue. In univariate analysis, nuclear expression of IL4Rα, cytoplasmic expression of IL4Rα, nuclear expression of IL13Rα1, and cytoplasmic expression of IL13Rα1 were significantly associated with shorter overall survival and shorter relapse-free survival. Multivariate analysis revealed nuclear expression of IL4Rα as an independent poor prognostic indicator of overall survival and relapse-free survival. Then, we found that knockdown of IL4Rα or IL13Rα1 decreased viability and induced apoptosis in SNU308 cells via activation of FOXO3 and similarly, AZD1480 decreased viability and induced apoptosis in SNU308 cells with dose dependent manner. CONCLUSIONS: Taken together, our results suggest that IL4Rα and IL13Rα1 might be involved in the development of human gallbladder cancer cells and IL4Rα and IL13Rα1 complex/JAK2 signaling pathway could be efficient therapeutic targets for gallbladder cancer treatment.

Unique Ultrasonographic Findings of Isolated IgG4-Related Lymphadenopathy.

IgG4-related disease is a rare immune-mediated disease that can involve many organs in the body. The lymph node is also where IgG4-related diseases occur, but its histological structure is different from that of other organs. For this reason, pathologists have difficulty diagnosing IgG4-related lymphadenopathy. If there were specific imaging findings of IgG4-related lymphadenopathy, it would be of great help to pathologists. A 64-year-old male visited our hospital with right ankle pain. On physical examination, the right lower extremity showed severe swelling with wound dehiscence, and infection was suspected. On CT (128-MDCT, Somatom Definition Flash, Siemens Healthcare) taken at the lower extremity, multiple enlarged lymph nodes were incidentally noted in the right inguinal area. On ultrasonography, a "starry night sign" resembling hyperechoic follicles was observed in the enlarged lymph node. A core needle biopsy was performed, and IgG4-related lymphadenopathy was diagnosed. Laboratory examination showed hypergammaglobulinemia with marked elevated serum IgG4, corresponding to IgG4-related disease. Chest and abdominal imaging were evaluated, but there was no extranodal IgG4-related disease. IgG4-related lymphadenopathy showed a very unique ultrasonography imaging finding. The cortex was filled with diffusely scattered hyperechoic foci and some bright foci gathered to form a follicle. This imaging finding may help diagnose IgG4-related lymphadenopathy.

Correlation of PIK3CA mutation with programmed death ligand-1 (PD-L1) expression and their clinicopathological significance in colorectal cancer.

BACKGROUND: The prognostic significance of PIK3CA mutations in colorectal cancer (CRC) remains controversial. Recently, an association between programmed death ligand-1 (PD-L1) and PIK3CA mutations has been reported. The study presented here was conducted to investigate the effect of PIK3CA mutations on the prognosis of CRC patients and the association between PIK3CA mutations and PD-L1. METHODS: PIK3CA mutations were analyzed by targeted next-generation sequencing using formalin-fixed paraffin-embedded specimens from 224 primary CRC patients. PD-L1 expression was evaluated by immunohistochemical staining. RESULTS: PIK3CA mutations and PD-L1 expression were detected in 21.4% and 10.3% of CRC patients, respectively. PIK3CA mutations were significantly correlated with right-side colon cancer (P=0.011) and were correlated inversely with lymph node metastasis (P=0.026), distant metastasis (P=0.047), and high TNM stage (P=0.036). In univariate analysis, PIK3CA mutations were correlated with longer relapse-free survival in CRC patients. PD-L1 expression was correlated significantly with PIK3CA mutations (P<0.001). CONCLUSIONS: PIK3CA mutations were associated with favorable prognostic factors, longer relapse-free survival, and expression of PD-L1. Further investigation is needed to identify whether PIK3CA mutations are a good prognostic factor. Additionally, further studies are needed to understand the mechanisms behind the correlation between PIK3CA mutations and PD-L1 expression.

FAM83H and Nectin1 expression are related with survival and relapse of bladder urothelial carcinoma patients.

BACKGROUND: FAM83H was originally reported to be essential for dental enamel formation. However, FAM83H has recently been implicated in tumorigenesis and tumor progression. Analysis of a publicly available gene expression database revealed a significant correlation between FAM83H and Nectin1 mRNA expression and bladder urothelial carcinoma (BUC). Therefore, we investigated the association between FAM83H and Nectin1 expression levels and the survival and recurrence of BUC in BUC patients using a tissue microarray. METHODS: We performed immunohistochemical staining of FAM83H and Nectin1 in 165 human BUC tissue sections, and analyzed the prognostic significance of FAM83H and Nectin1 expression. RESULTS: Both FAM83H and Nectin1 were mainly expressed in the cytoplasm, and their expression was significantly associated. FAM83H expression was significantly correlated with higher histologic grade, higher T stage, higher TNM stage, and recurrence. Nectin1 expression was significantly associated with higher histologic grade and recurrence. Univariate analysis showed FAM83H expression and Nectin1 expression were significantly associated with worse overall survival (OS) and shorter relapse-free survival (RFS) of BUC patients. In multivariate analysis, levels of FAM83H and Nectin1 were independent indicators of shorter survival of BUC patients. CONCLUSIONS: Our results suggest that FAM83H and Nectin1 are important in the progression of BUC, and that expression patterns of these two proteins can be used as prognostic indicators of survival in BUC patients.