Adipophilin Expression Research Articles

Association between adipophilin expression and risk of dyslipidaemia in patients with granuloma annulare

BackgroundAn association between granuloma annulare (GA) and dyslipidaemia has been reported. Adipophilin expression may play a plausible role as a cutaneous biomarker for dyslipidaemia in patients with GA; however, this potential link remains to be explored. MethodsPatients with GA were identified at our hospital between January 1, 1990, and December 31, 2021, with a thorough review of their clinical and histological characteristics. Adipophilin staining was assessed in biopsies of GA lesions. ResultsA total of 107 patients with GA were included. The prevalence of dyslipidaemia in patients with positive adipophilin staining was clearly higher than in those with negative labelling (62.3% vs 13.3%). Relative to the dyslipidaemia risk for patients with negative adipophilin expression, the odds for patients with positive adipophilin expression were increased 10-fold (OR: 10.8; p-value<.01). We identified 23 incident cases of dyslipidaemia over a median follow-up period of 91 months among 54 patients with no history of dyslipidaemia. The patients with positive adipophilin expression showed a higher risk of developing dyslipidaemia (HR: 8.9; p-value<.01). ConclusionsPatients with positive adipophilin staining in their GA biopsies were found to be associated with a higher risk for both baseline and incident dyslipidaemia.

Cytoplasmic Lipid Droplets Predict Worse Prognosis in Diffuse Large B-Cell Lymphoma: Next-Generation Sequencing Deciphering Lipogenic Genes.

Burkitt lymphoma is characterized by high cell turnover and numerous cytoplasmic vacuoles that are demonstrated to be lipid droplets (LDs) decorated by adipophilin. By contrast, cytoplasmic vacuoles are variably observed in diffuse large B-cell lymphoma (DLBCL) and less well characterized. In this study, we first validated in DLBCL that cytoplasmic vacuoles are indeed LDs by Oil-red-O stain, Bodipy fluorescent stain, and electron microscopy. Second, in a cohort of DLBCL patients (n=52) we showed that LDs in effusional lymphoma cells were associated with a poorer prognosis (P=0.029, log-rank test) and higher International Prognostic Index (IPI) score (94% vs. 66%, P=0.026) than those without. Moreover, using adipophilin as a surrogate marker for LDs, we found in another cohort of biopsy specimen (n=85) that expression of adipophilin by lymphoma cells predicted a poorer prognosis (P=0.007, log-rank test) and higher IPI score (63% vs. 30%, P=0.005). In addition, whole exome sequencing of effusional DLBCL cells showed LD-positive DLBCL shared genetic features with the MCD (MYD88 and CD79B mutations) subtype and highlighted OSBPL10 and CUBN as the most frequently mutated genes involved in lipogenesis. Whole transcriptome analysis by comparing effusional DLBCL cells with versus without LDs showed upregulation of EHHADH, SLC1A1, CD96, INPP4B, and RNF183 relevant for lymphoma lipogenesis and upregulation of epithelial-mesenchymal transition and KRAS signaling pathways. Higher expression of EHHADH and CD96 were validated in LD-positive clinical samples and LD-rich cell lines than LD-poor cells along with the known lipogenic gene, FASN. Our findings highlight the roles of LDs and adipophilin expression in DLBCL, suggest that these markers may predict prognosis and show that lipogenic genes may be potential therapeutic targets.

Malignant mesothelioma cells with characteristic intracytoplasmic vacuolization and lipids.

In this brief report, we described some uncommon cytomorphological features of malignant mesothelioma (MM) cells in pleural effusions. The tumor cells exhibited abundant cytoplasmic vacuolization, with presence of single or multiple eccentric nuclei in several cells. In the Giemsa-stained smear, we observed a glossy spherical material in some cells, which tested positive in Sudan III stain. In immunocytochemical analysis, tumor cells were positive for calretinin, podoplanin, epithelial membrane antigen, and methylthioadenosine phosphorylase; tumor cells were negative for BRCA1-associated protein 1, CD68, and desmin. The intracytoplasmic vacuoles were positive for adipophilin expression.

Ocular and extraocular sebaceous carcinomas: A retrospective study with emphasis on the presence of insitu lesion and discussion and review of the histogenesis of extraocular sebaceous carcinoma.

Sebaceous carcinoma (SC) is a rare carcinoma classified as ocular or extraocular. Ocular SC is believed to arise from the meibomian glands or the glands of Zeis. However, the origin of extraocular SC is controversial because there is no evidence of carcinoma arising from pre-existing sebaceous glands. Several hypotheses about the origin of extraocular SC have been proposed, including one suggesting an origin from intraepidermal neoplastic cells. Although extraocular SCs have been shown to occasionally comprise intraepidermal neoplastic cells, no study has investigated whether intraepidermal neoplastic cells possess sebaceous differentiation. The present study analyzed the clinicopathological features of ocular and extraocular SC, with an emphasis on the presence of in situ (intraepithelial) lesions. It retrospectively reviewed the clinicopathological features of eight patients with ocular and three patients with extraocular SC (eight women and three men; median age, 72 years), respectively. In situ (intraepithelial) lesions were observed in four of the eight ocular SC cases and one of the three extraocular SC cases and an apocrine component was noted in one patient with ocular SC (seboapocrine carcinoma). In addition, immunohistochemical analyses showed that the androgen receptor (AR) was expressed in all ocular SCs and two of the three extraocular SC cases. Adipophilin expression was observed in all ocular and extraocular SC. In situ lesions of extraocular SC showed positive immunoreactivity for both AR and adipophilin. The present study is the first to demonstrate sebaceous differentiation in in situ lesions of extraocular SC. The possible origin of extraocular SC is speculated to be the progenitor cells present in the sebaceous duct or interfollicular epidermis. The results of the present study and reported cases of SC in situ indicate that extraocular SC also arises from intraepidermal neoplastic cells.

Novel prognostication biomarker adipophilin reveals a metabolic shift in uveal melanoma and new therapeutic opportunities.

Metastatic uveal melanoma remains incurable at present. We previously demonstrated that loss of BAP1 gene expression in tumour cells triggers molecular mechanisms of immunosuppression in the tumour microenvironment (TME) of metastatic uveal melanoma. Adipophilin is a structural protein of lipid droplets involved in fat storage within mammalian cells, and its expression has been identified in uveal melanoma. We comprehensively evaluated adipophilin expression at the RNA (PLIN2) and protein levels of 80 patients of the GDC-TCGA-UM study and in a local cohort of 43 primary uveal melanoma samples respectively. PLIN2 expression is a survival prognosticator biomarker in uveal melanoma. Loss of adipophilin expression is significantly associated with monosomy 3 status and nuclear BAP1 losses in uveal melanoma tumours. Integrative transcriptomic and secretome studies show a relationship between transient loss of adipophilin expression and increased levels of tumour-associated macrophages and hypoxia genes, suggesting PLIN2-dependent changes in oxygen and lipid metabolism in the TME of low and high-metastatic risk uveal melanoma. We designed four adipophilin-based multigene signatures for uveal melanoma prognostication using a transcriptomic and secretome survival-functional network approach. Adipophilin-based multigene signatures were validated in BAP1-positive and BAP1-negative uveal melanoma cell lines using a next-generation RNA sequencing approach. We identified existing small molecules, mostly adrenergic, retinoid, and glucocorticoid receptor agonists, MEK, and RAF inhibitors, with the potential to reverse this multigene signature expression in uveal melanoma. Some of these molecules were able to impact tumour cell viability, and carvedilol, an adrenergic receptor antagonist, restored PLIN2 levels, mimicking the expression of normoxia/lipid storage signatures and reversing the expression of hypoxia/lipolysis signatures in co-cultures of uveal melanoma cells with human macrophages. These findings open up a new research line for understanding the lipid metabolic regulation of immune responses, with implications for therapeutic innovation in uveal melanoma. © 2023 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

Upregulated MYC expression and p53 mutations may contribute to the oncogenesis of canine Meibomian gland carcinomas.

Sebaceous carcinomas of the human ocular adnexa commonly exhibit pagetoid spread, mutations in tumor-suppressor genes, and protooncogene copy number gain. Sebaceous carcinomas are rarely reported in other species, and while the Meibomian gland (MG) represents the most common ocular adnexal structure of the canine eyelid to develop neoplasia, most are clinically and histologically benign. The objective of this study was to compare molecular features of canine MG carcinomas and adenomas. Two retrospectively identified MG carcinomas were subject to immunohistochemistry and qPCR. When compared with normal glands, MYC was upregulated in benign and malignant MG neoplasms. Aberrant p53 expression was restricted to the nuclei of intraepithelial neoplastic cells in MG carcinomas. Adipophilin expression was diminished in MG neoplasms compared with the normal MG. Our findings, if confirmed in a larger cohort of cases, could suggest that MG oncogenesis in a dog may exhibit similar molecular features as their human counterparts.

Lipid droplet accumulation and adipophilin expression in follicular thyroid carcinoma

Follicular neoplasms of the thyroid include follicular thyroid carcinoma (FTC) and follicular thyroid adenoma (FTA). However, the differences in cytological findings between FTC and FTA remain undetermined. Here, we aimed to evaluate the accumulation of lipid droplets (LDs) and the expression of adipophilin (perilipin 2/ADRP/ADFP), a known LD marker, in cultured FTC cells. We also immunohistochemically compared adipophilin expression in the FTC and FTA of resected human thyroid tissues. Cultured FTC (FTC-133 and RO82W-1) possessed increased populations of LDs compared to thyroid follicular epithelial (Nthy-ori 3-1) cells. In vitro treatment with phosphatidylinositol-3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) signaling inhibitors (LY294002, MK2206, and rapamycin) in FTC-133 cells downregulated the PI3K/Akt/mTOR/sterol regulatory element-binding protein 1 (SREBP1) signaling pathway, resulting in a significant reduction in LD accumulation. SREBP1 is a master transcription factor that controls lipid metabolism. Fluorescence immunocytochemistry revealed adipophilin expression in the LDs of FTC-133 cells. Immunohistochemical analysis of surgically resected human thyroid tissues revealed significantly increased expression of adipophilin in FTC compared with FTA and adjacent non-tumorous thyroid epithelia. Taken together, LDs and adipophilin were abundant in cultured FTC; the evaluation of adipophilin expression can help distinguish FTC from FTA in surgical specimens.

Prognostic significance of adipophilin expression in biopsy specimens of patients with triple-negative breast cancer.

Triple-negative breast cancer (TNBC) is the most aggressive type of breast cancer. The present authors recently demonstrated that expression of the lipid-related protein adipophilin (ADP) in operative specimens is a significant poor prognostic factor in patients with TNBC. Using biopsy specimens is important in making clinical decisions for patients with breast cancer; however, the prognostic significance of ADP expression in biopsy specimens from TNBC patients remains unclear. The present study determined the prognostic significance of ADP expression in biopsy specimens from TNBC patients and compared ADP-expression status between biopsy and operative specimens. The present study analyzed ADP-expression profiles in biopsy specimens from 102 patients with TNBC using immunohistochemical staining and determined relapse-free survival and risk factors associated with ADP expression in these specimens, as well as the concordance of ADP expression between biopsy and operative specimens. The results identified ADP expression in 35.3% of biopsy specimens from TNBC patients. The Ki-67 labelling index was significantly higher in ADP-positive patients (P<0.001). Univariate analysis revealed that ADP expression in biopsy specimens was significantly associated with poor relapse-free survival in patients not administered neoadjuvant chemotherapy or adjuvant chemotherapy (P=0.026). Furthermore, the concordance rate of ADP expression between biopsy and operative specimens was 73.1%, with a Cohen's kappa coefficient of 0.385 (P=0.003). These findings suggested that ADP expression in biopsy specimens might be a useful prognostic marker for patients with TNBC and could potentially provide important information regarding treatment strategies for these patients.

Association between fatty acid synthase and adipophilin expression in triple-negative breast cancer.

It is well known that cancer cells produce energy via anaerobic glycolysis. Lipid metabolism is often upregulated in numerous types of cancer. Our previous study demonstrated that adipophilin (ADP), a lipid-associated protein, was a poor prognostic indicator in patients with triple-negative breast cancer (TNBC). However, the mechanism of ADP expression in TNBC remains unclear. Fatty acid synthase (FASN) is a crucial enzyme in de novo fatty acid synthesis, and its upregulation has been reported in several types of carcinomas; however, to the best of our knowledge, the association of FASN and ADP in TNBC remains unclear. The present study analysed the association between FASN and ADP expression and the prognostic significance of FASN in TNBC. Using immunohistochemical methods and tissue microarrays, the present study examined FASN expression in 61 patients with TNBC. Overall and relapse-free survival and their risk factors were analysed for FASN expression and compared with ADP expression. A total of 40 (65.6%) patients were classified as FASN-high (score ≥120), and this was significantly associated with a lower Ki-67 labelling index (P=0.011). FASN expression was not associated with relapse-free survival and overall survival. FASN-high was negatively associated with ADP expression (P=0.041). The results of the present study revealed that FASN-high was associated with a lack of ADP expression and a lower Ki-67 labelling index. These results indicated that de novo fatty acid synthesis by FASN is not the main pathway of lipogenesis and the source of energy in cancer cells of ADP-positive highly proliferative TNBC.

Adipophilin expression in skin lesions with clear cell histology

AimsClear cells formed due to depositions of glycogen or lipids in the cytoplasm commonly occur in various tissues. Adipophilin (ADP), a lipid regulatory protein, is closely related to lipid droplets....

Branched-chain amino acids and l-carnitine attenuate lipotoxic hepatocellular damage in rat cirrhotic liver

Branched-chain amino acids (BCAA) reverse malnutrition and l-carnitine leads to the reduction of hyperammonemia and muscle cramps in cirrhotic patients. BCAA and l-carnitine are involved in glucose and fatty acid metabolism, however their mechanistic activity in cirrhotic liver is not fully understood. We aim to define the molecular mechanism(s) and combined effects of BCAA and l-carnitine using a cirrhotic rat model. Rats were administered carbon tetrachloride for 10 weeks to induce cirrhosis. During the last 6 weeks of administration, cirrhotic rats received BCAA, l-carnitine or a combination of BCAA and l-carnitine daily via gavage. We found that BCAA and l-carnitine treatments significantly improved hepatocellular function associated with reduced triglyceride level, lipid deposition and adipophilin expression, in cirrhotic liver. Lipidomic analysis revealed dynamic changes in hepatic lipid composition by BCAA and l-carnitine administrations. BCAA and l-carnitine globally increased molecular species of phosphatidylcholine. Liver triacylglycerol and phosphatidylcholine hydroperoxides were significantly decreased by BCAA and l-carnitine. Furthermore, serum and liver ATP levels were significantly increased in all treatments, which were attributed to the elevation of mature cardiolipins and mitochondrial component gene expressions. Finally, BCAA and l-carnitine dramatically reduced hepatocellular death. In conclusion, BCAA and l-carnitine treatments attenuate hepatocellular damage through the reduction of lipid peroxides and the overall maintenance of mitochondrial integrity within the cirrhotic liver. These effectiveness of BCAA and l-carnitine support the therapeutic strategies in human chronic liver diseases.

Adipophilin expression is an independent marker for poor prognosis of patients with triple-negative breast cancer: An immunohistochemical study.

Adipophilin is a lipid droplet-associated protein whose expression can act as a prognostic marker for specific cancers. Using immunohistochemical staining and tissue microarrays, we assayed the expression of adipophilin in 61 patients with triple-negative breast cancer (TNBC) who underwent surgery from January 2006-December 2018. Relapse-free survival (RFS) and its risk factors were analyzed based on adipophilin expression. Fourteen (23.0%) patients expressed adipophilin. As compared to the adipophilin-negative TNBC patients, adipophilin-positive patients exhibited poor RFS (p = 0.032). Among the TNBC patients with a high Ki-67 labeling index, patients negative for adipophilin exhibited better RFS than patients positive for adipophilin (p = 0.032). Moreover, among patients who did not undergo adjuvant chemotherapy, patients negative for adipophilin expression exhibited better RFS than adipophilin-positive patients (p = 0.080). Multivariate analysis showed that adipophilin expression correlated with a high rate of relapse (hazard ratio, 4.89; 95% confidence interval, 1.04-23.0; p = 0.044). Taken together, these results indicate that adipophilin is a novel marker for the poor prognosis of patients with TNBC.

Adipophilin expression as an independent marker for poor prognosis of patients with triple-negative breast cancer.

e12552 Background: Adipophilin (ADP) is a lipid-regulating protein of the perilipin/adipophilin/tail interacting protein of 47 kDa (PAT) family that coats the surfaces of cytoplasmic lipid droplets. Lipids are essential for cellular proliferation in tumor cells, and ADP, which increases the efficiency of lipid use, may contribute to cancer growth. Some previous studies suggest that ADP expression can act as a prognostic marker for specific cancers. The aim of this study is to investigate the clinicopathological significance of ADP expression in patients with triple-negative breast cancer (TNBC). Methods: Using immunohistochemical staining and tissue microarrays, we analyzed the expression profiles of ADP, glutaminase, and glutamate dehydrogenase (key enzymes in glutamine metabolism) in 61 TNBC patients who underwent operation from January 2006–December 2018. Relapse-free survival (RFS) was compared based on ADP expression and the risk factors for RFS were analyzed. Results: Fourteen (23.0%) patients were ADP-positive. As compared to ADP-negative TNBC patients, ADP-positive TNBC patients correlated with poor RFS ( p = 0.032). Among the TNBC patients with high Ki-67 labeling index, those negative for ADP exhibited better RFS than those positive for ADP ( p = 0.049). Moreover, among the patients without adjuvant chemotherapy, those negative for ADP exhibited better RFS than those positive for ADP ( p = 0.080). ADP-positive patients correlated with a significantly higher recurrence based on multivariate analyses (hazard ratio, 4.89; 95% confidence interval, 1.04–23.0; p = 0.044). Moreover, ADP expression significantly correlated with the expression of glutaminase and glutaminate dehydrogenase ( p &lt; 0.001 and p = 0.029, respectively). Conclusions: ADP expression is a novel marker for poor prognosis of patients with TNBC and might be superior to Ki-67 as a prognostic marker. ADP expression may be related to upregulation of glutamine metabolism in cancer cells of TNBC.

Adipophilin expression in cutaneous malignant melanoma is associated with high proliferation and poor clinical prognosis

AbstractAdipophilin (ADP) is a primary protein component of lipid droplets (LDs). For more than half a century, certain types of cancer cells have been known to contain LDs in their cytoplasm. However, the pathological significance of ADP or LDs in cancer remains unclear. In the present study, we investigated the association between ADP and other pathological characteristics in cutaneous malignant melanomas to clarify the role of ADP in melanoma cells. We immunostained whole paraffin sections of primary cutaneous melanomas obtained from 90 cases for ADP, after which we analyzed the correlation between ADP immunohistochemistry (IHC) and patient survival data. We also studied the relationship between the ADP IHC score and in situ hybridization (ISH) score of ADP mRNA, and the Ki67-labeling index (Ki67-LI) by using tissue microarrays consisting of 74 primary cutaneous malignant melanomas, 19 metastasizing melanomas, and 29 melanocytic nevi. Finally, we analyzed the relationship between ADP expression and cell proliferation in cutaneous melanoma cell lines. We found that high ADP expression was associated with poor metastasis-free survival, disease-specific survival, and overall survival rates of patients with cutaneous melanomas (P < 0.05). By linear regression analysis, ADP IHC was correlated with increasing ADP mRNA ISH H-scores and Ki67-LI scores in melanocytic lesions (P < 0.01). ADP IHC and ADP ISH H-scores and Ki67-LI scores were greater in pT3–4 melanomas than in pT1–2 melanomas. In cell-based assays, cells with increased ADP expression showed higher proliferation rates compared with those of low-ADP cells. Thus, ADP expression in malignant melanoma was significantly associated with high cell proliferation and poor clinical prognosis. Our results thus indicate a significant association between ADP and melanoma progression, and we propose that ADP may be a novel marker of aggressive cutaneous melanoma with a lipogenic phenotype.

The clinicopathological significance of the adipophilin and fatty acid synthase expression in salivary duct carcinoma

Salivary duct carcinoma (SDC) is an aggressive, uncommon tumor histologically comparable to high-grade mammary ductal carcinoma. SDCs are usually androgen receptor (AR)–positive and often HER2-positive. Recently, therapies targeting these molecules for SDC have attracted attention. Lipid metabolism changes have been described in association with biological behavior in various cancers, although no such relationship has yet been reported for SDC. We therefore analyzed the clinicopathological relevance of the immunohistochemical expression of adipophilin (ADP) and fatty acid synthase (FASN), representative lipid metabolism–related proteins, in 147 SDCs. ADP and FASN were variably immunoreactive in most SDCs (both 99.3%), and the ADP and FASN expression was negatively correlated (P = 0.014). ADP-positive (≥ 5%) SDCs more frequently exhibited a prominent nuclear pleomorphism and high-Ki-67 labeling index than those ADP-negative (P = 0.013 and 0.011, respectively). In contrast, a high FASN score, calculated by the staining proportion and intensity, (≥ 120) was correlated with the high expression of AR and FOXA1 (P < 0.001 and = 0.003, respectively). The ADP and FASN expression differed significantly among the subtypes based on biomarker immunoprofiling, as assessed by the AR, HER2, and Ki-67 status (P = 0.017 and 0.003, respectively). A multivariate analysis showed that ADP-positive expression was associated with a shorter overall and progression-free survival (P = 0.018 and 0.003, respectively). ADP was associated with an aggressive histopathology and unfavorable prognosis, and FASN may biologically interact with the AR signaling pathway in SDC. ADP may, therefore, be a new prognostic indicator and therapeutic target in SDC.

Analysis of the Expression of Genes Related to Lipidic and Glycogenic Metabolism in Pleomorphic Adenomas and Carcinomas Ex Pleomorphic Adenomas

Abstract Introduction The carcinoma ex pleomorphic adenoma (CXPA) arises from a pleomorphic adenoma (PA) and is supposed to gain lipogenesis and glycogenesis during its malignant transformation. Increased lipogenesis is a characteristic of cancer cells, consisting of increased fatty acid synthesis by the enzyme fatty acid synthase (FASN) and by the accumulation of cytoplasmic lipid droplets, which express adipophilin. The increase in glycolytic metabolism has been associated with the activity of glycolytic enzymes and glucose transporters (GLUTs), whose expression is induced by HIF-1 (inducing factor of hypoxia 1). Objectives To analyze the gene expression of FASN, adipophilin, HIF-1α, and GLUT-1 in PA and CXPA samples. Methodology Gene expression analysis of the FASN, adipophilin, HIF1-α, and GLUT-1 genes was performed by the real-time PCR (qPCR) method. Fourteen cases of PA and 14 cases of CXAP were evaluated. Results FASN, adipophilin, HIF-1α, and GLUT-1 were more expressed in CXAP than in AP, although there was no significant difference between levels of adipophilin expression in CXPA and PA. Conclusion Increased expression of FASN, HIF1-α, and GLUT-1 in CXAP may be associated with malignant transformation of PA, while additional studies are needed to understand the role of adipophilin in PA carcinogenesis. Moreover, this is the first study to investigate the role of these genes in the malignant transformation of PA.

Role of magnetic resonance DTI in PDAC evaluation

Adipophilin is a lipid droplet-associated protein, and its expression has been correlated with aggressive clinical behavior in some types of carcinomas, though its role in pancreatic ductal adenocarcinoma (PDAC) has not been clarified. This study aimed to evaluate the role of adipophilin in PDAC.By immunohistochemical staining using tissue microarrays, we analyzed the expression profiles of adipophilin in 181 consecutive PDAC patients who underwent macroscopic margin-negative resection from January 2008 to December 2015. Overall survival (OS) and recurrence-free survival (RFS) were compared based on adipophilin expression, and the risk factors for OS, RFS, and early recurrence (within 6 months) were analyzed.Of the 181 evaluated patients, 51 (28.2%) were positive for adipophilin expression. A histopathological grade of 3 (p = 0.0012), higher CA19-9 level (p = 0.0016), and R1 status (p = 0.028) were significantly associated with adipophilin-positive patients who had significantly poor OS and RFS compared to those associated with adipophilin-negative patients (p = 0.0007 and p = 0.0022, respectively). They also showed a significantly higher incidence of early recurrence (p = 0.030), based on multivariate analyses.Adipophilin is a potential independent prognostic marker for PDAC.

Adipophilin expression is an indicator of poor prognosis in patients with pancreatic ductal adenocarcinoma: An immunohistochemical analysis

ObjectiveAdipophilin is a lipid droplet-associated protein, and its expression has been correlated with aggressive clinical behavior in some types of carcinomas, though its role in pancreatic ductal adenocarcinoma (PDAC) has not been clarified. This study aimed to evaluate the role of adipophilin in PDAC. MethodsBy immunohistochemical staining using tissue microarrays, we analyzed the expression profiles of adipophilin in 181 consecutive PDAC patients who underwent macroscopic margin-negative resection from January 2008 to December 2015. Overall survival (OS) and recurrence-free survival (RFS) were compared based on adipophilin expression, and the risk factors for OS, RFS, and early recurrence (within 6 months) were analyzed. ResultsOf the 181 evaluated patients, 51 (28.2%) were positive for adipophilin expression. A histopathological grade of 3 (p = 0.0012), higher CA19-9 level (p = 0.0016), and R1 status (p = 0.028) were significantly associated with adipophilin-positive patients who had significantly poor OS and RFS compared to those associated with adipophilin-negative patients (p = 0.0007 and p = 0.0022, respectively). They also showed a significantly higher incidence of early recurrence (p = 0.030), based on multivariate analyses. ConclusionsAdipophilin is a potential independent prognostic marker for PDAC.

The Expression of Adipophilin Is Frequently Found in Solid Subtype Adenocarcinoma and Is Associated with Adverse Outcomes in Lung Adenocarcinoma.

BackgroundThe up-regulation of the lipogenic pathway has been reported in many types of malignant tumors. However, its pathogenic role or clinical significance is not fully understood. The objective of this study was to examine the expression levels of adipophilin and related hypoxic signaling proteins and to determine their prognostic impacts and associations with the pathologic characteristics of lung adenocarcinoma.MethodsExpression levels of adipophilin, heat shock protein 27 (HSP27), carbonic anhydrase IX, and hypoxia-inducible factor 1α were examined by immunohistochemical staining using tissue microarray blocks. Correlations between protein expression levels and various clinicopathologic features were analyzed.ResultsA total of 230 cases of primary adenocarcinoma of the lung were enrolled in this study. Adipophilin expression was more frequent in males and with the solid histologic type. It was correlated with HSP27 expression. Patients with adipophilin-positive adenocarcinoma showed a shorter progression-free survival (PFS) (median PFS, 17.2 months vs 18.4 months) in a univariable survival analysis, whereas HSP27 positivity correlated with favorable overall survival (OS) and PFS. In a multivariable analysis, adipophilin and HSP27 were independent prognostic markers of both OS and PFS.ConclusionsActivated lipid metabolism and the hypoxic signaling pathway might play a major role in the progression of lung adenocarcinoma, especially in the solid histologic type.

Association between white opaque substance under magnifying colonoscopy and lipid droplets in colorectal epithelial neoplasms.

AIMTo examine the association between white opaque substance (WOS) and histologically verified lipid droplets in colorectal epithelial neoplasms.METHODSWe reviewed colonoscopy records at our institution from 2014 to 2016 and identified cases of endoscopically or surgically resected colorectal epithelial neoplasms observed by magnifying narrow-band imaging (M-NBI) colonoscopy. Immunohistochemistry was used to stain tumors with a monoclonal antibody specific to adipophilin as a marker of lipids. The expression and distribution of adipophilin were compared between WOS-positive and WOS-negative lesions and among tumors classified by histologic type and depth of invasion.RESULTSUnder M-NBI colonoscopy, 81 lesions were positive for WOS and 48 lesions were negative for WOS. The rate of adipophilin expression was significantly higher in WOS-positive lesions (95.1%) than in WOS-negative lesions (68.7%) (P = 0.0001). The incidence of deep adipophilin expression was higher in WOS-positive lesions (24.7%) than in WOS-negative lesions (4.2%) (P = 0.001). The incidence of deep expression was predominant among cancers with massive submucosal invasion (62.5%) compared to adenoma (7.2%) and high-grade dysplasia or cancers with slight submucosal invasion (12.7%) (P = 0.0001).CONCLUSIONThe distribution of lipid droplets may be closely associated with the visibility of WOS under M-NBI colonoscopy, and with histologic grade and depth of tumor invasion.