Significance of Altered Fatty Acid Transporter Expressions in Uterine Cervical Cancer and Its Precursor Lesions.

BACKGROUND: High-risk human papilloma virus (HR HPV) infection is a major factor leading to the development of uterine cervical cancer. Data suggest that alterations in lipid metabolism are related to the pathogenesis of cervical cancer. Specifically, the uptake of exogenous fatty acids and their intracellular storage in lipid droplets enables cancer cells to survive and adapt to the changing tumor environment. MATERIALS AND METHODS: We compared the immunohistochemical expression of fatty acid transport protein 4 (FATP4), and cluster of differentiation 36/fatty acid translocase (CD36/FAT) in normal cervical epithelium, low-grade squamous intraepithelial lesion (LSIL), high-grade squamous intraepithelial lesion (HSIL), and squamous cell carcinoma (SCC) tissues of the uterine cervix. We also investigated the clinicopathological implications of these fatty acid transporters in SCC. RESULTS: Compared with that in normal cervical tissues, the expression of FATP4 was lower in LSIL (p=0.002), HSIL (p=0.006), and SCC (p=0.001). In contrast, CD36 expression was higher in SCC tissues than in normal cervical tissues (p<0.001). In normal cervical tissues, HR HPV-infected lesions exhibited a decrease in FATP4 (p<0.001) and an increase of CD36 (p=0.134), compared to those that were not infected with HR HPV. High CD36 expression was associated with a shorter recurrence-free survival (p<0.001). However, high FATP4 levels showed no significant correlation with the clinicopathological parameters of SCC. CONCLUSION: Altered expression levels of FATP4 and CD36 are unique features that might be related to HR HPV infection and promote tumorigenesis and progression of cervical cancer.

Upregulation of Fatty Acid Transporters is Associated With Tumor Progression in Non-Muscle-Invasive Bladder Cancer.

As patients with non-muscle-invasive bladder cancer (NMIBC) show a high degree of heterogeneity in tumor recurrence or progression, many clinicians demand a detailed risk stratification. Although modified fatty acid metabolism in cancer cells is reported to reflect malignant phenotypes such as metastasis, the impact of fatty acid transporters on NMIBC has never been investigated. This study examined the clinicopathologic implications of fatty acid transporters such as fatty acid transport protein 4 (FATP4), cluster of differentiation 36/fatty acid translocase (CD36/FAT), and long chain acyl CoA synthetase 1 (ACSL1) in 286 NMIBC cases. This study revealed that FATP4, CD36, and ACSL1 were overexpressed in 123 (43.0%), 43 (15.0%), and 35 (12.2%) NMIBC cases, respectively. High FATP4 in tumor cells was associated with high grade (p = 0.004) and high stage (p = 0.039). High CD36 was related to high grade (p < 0.001), high stage (p = 0.002), and non-papillary growth type (p = 0.004). High ACSL1 showed an association with high grade (p < 0.001), high stage (p = 0.01), non-papillary growth type (p = 0.002), and metastasis (p = 0.033). High FATP4 was an independent factor predicting short overall survival (OS) (hazard ratio = 3.32; 95% confidence interval, 1.07-10.31; p = 0.038). In conclusion, upregulation of FATP4, CD36, and ACSL1 might promote the NMIBC progression and could be exploited in clinical risk stratification and targeted therapy.

Increased expression levels of AURKA and KIFC1 are promising predictors of progression and poor survival associated with gastric cancer.

Increased cell proliferation is a critical hallmark of cancer development and progression. The proliferation of tumor cells depends on mitotic deregulation. Here, we identified the differentially expressed genes (DEGs) in gastric cancer (GC) through RNA sequencing data and bioinformatics analysis. Subsequent functional and pathway enrichment analyses showed that the screened DEGs were enriched in the mitosis-associated pathway. Based on the analysis results, we selected two signatures (aurora kinase A [AURKA] and kinesin family member C1 [KIFC1]) to determine their clinicopathological significance. The results showed a significant positive correlation between AURKA and KIFC1 expression both at the mRNA and protein levels. AURKA expression was positively correlated with distant metastases (p = 0.032) and tumor-node-metastasis (TNM) stage (p = 0.001). Elevated KIFC1 expression was significantly associated with tumor size (p = 0.029), depth of invasion (p < 0.001), lymph node metastasis (p < 0.001), distant metastasis (p = 0.023), and TNM stage (p < 0.001). Higher AURKA (hazard ratio [HR] = 1.3, p < 0.001) and KIFC1 (HR = 1.41, p < 0.001) mRNA levels were also significantly correlated with poor overall survival. Thus, AURKA and KIFC1 could serve as potential prognostic markers and therapeutic targets for GC.

Increased HOXC6 mRNA expression is a novel biomarker of gastric cancer.

In this study, we aimed to investigate the molecular biomarkers that are pivotal for the development and progression of gastric cancer (GC). We analyzed clinical specimens using RNA sequencing to identify the target genes. We found that the expression of HOXC6 mRNA was upregulated with the progression of cancer, which was validated by quantitative real time PCR and RNA in-situ hybridization. To compare the protein expression of HOXC6, we evaluated GC and normal gastric tissue samples using western blot analysis and immunohistochemistry. We detected significantly higher levels of HOXC6 in the GC tissues than in the normal controls at both mRNA and protein levels. The expression levels of HOXC6 mRNA in patients with advanced gastric cancer (AGC) were significantly higher than those in patients with early gastric cancer (EGC). Kaplan-Meier curves showed that high expression of HOXC6 mRNA is significantly associated with poor clinical prognosis. Our findings suggest that HOXC6 mRNA may be a novel biomarker and can be potentially valuable in predicting the prognosis of GC patients. Especially, HOXC6 mRNA in-situ hybridization may be a diagnostic tool for predicting prognosis of individual GC patients.

Protein expression profiles and prognostic value of E2F family members in clear cell renal cell carcinoma.

The derangement of the cell cycle facilitates uncontrolled cell proliferation and acquisition of genetic alterations favorable for malignancy. However, the protein expression profiles of E2 F family cell cycle regulators in clear cell renal cell carcinoma (ccRCC) have not yet been thoroughly investigated. In this study, we aimed to examine the protein expression profiles and prognostic value of E2 F1, E2 F3, and E2 F4 in ccRCC cases. The immunohistochemical expression of E2 F1, E2 F3, and E2 F4 was quantitatively scored in 180 ccRCC tumor tissues and 79 normal kidney tissues. The prognostic implications of these E2 F members were determined. We found that ccRCC tumor cells showed higher nuclear expression of E2 F1, E2 F3 and E2 F4 than normal kidney samples. High E2 F1 and E2 F3 expression in tumor cells was associated with poor prognostic factors of ccRCC, whereas high E2 F4 correlated with beneficial prognostic factors. High expression of E2 F1 and E2 F3 in tumor cells was correlated with a poor overall and recurrence-free survival, while high E2 F4 expression did not. In conclusion, E2 F1, E2 F3 and E2 F4 may function as oncogenes during tumorigenesis of ccRCC, although they contribute to the progression of ccRCC in different ways. Additional studies are required to clarify the conflicting role of E2 F4 in the tumor evolution of ccRCC.

Herpes Simplex Mastitis in an Adolescent Woman: Clinical and Ultrasound Features.

Herpetic mastitis is extremely rare, and its imaging findings remain unclear. We report a case of herpes simplex mastitis in an adolescent woman and describe the clinical and ultrasound features. The patient showed unilateral nipple and areolar skin thickening and axillary lymphadenopathy on B-mode ultrasonography. Doppler ultrasonography revealed multiple linear and branching blood flows in the areolar area. The lesion was verified as herpes simplex mastitis via a skin biopsy. This report shows that the radiologic features of herpes simplex mastitis may be similar to those of Paget's disease because of localized nipple and areolar skin thickening and increased vascularity.

High Membranous Expression of Fatty Acid Transport Protein 4 Is Associated with Tumorigenesis and Tumor Progression in Clear Cell Renal Cell Carcinoma.

The increased requirement of fatty acids forces cancer cells to enhance uptake of fatty acids from the extracellular milieu, in addition to de novo lipogenesis. Coexpression of cluster of differentiation 36 (CD36) with fatty acid transport protein 4 (FATP4) or long-chain acyl CoA synthetase 1 (ACSL1) synergistically activated fatty acid uptake in experimental models. In this study, we investigated the immunohistochemical expression of CD36, FATP4, and ACSL1 in 180 cases of clear cell renal cell carcinoma (RCC) in comparison with 80 specimens of the normal kidney. We also examined the clinical implication of these three fatty acid transporters in RCC, which was validated by an open-access The Cancer Genome Atlas data analysis. Both CD36 and FATP4 revealed higher membranous expressions in RCC tumor cells than in normal cells. In contrast, ACSL1 expression was remarkably reduced in RCC tumor cells compared to normal cells. CD36, FATP4, and ACSL1 showed high expressions in 74 (41.1%), 85 (47.2%), and 72 (40.0%) out of 180 RCC cases, respectively. Clinically, high FATP4 in tumor cells was associated with female gender (p = 0.05), high TNM stage (p = 0.039), tumor necrosis (p = 0.009), and tumor recurrence (p = 0.037), while high ACSL1 was only related to female gender (p = 0.023). CD36 expression revealed no correlation with the clinicopathologic parameters of RCC. Increased FATP4 expression displayed an association with short recurrence-free survival (p = 0.003). In conclusion, the high FATP4 expression was clinically associated with poor prognostic factors of RCC. Overexpression of membranous FATP4 and CD36 combined with reduced cytoplasmic expression of ACSL1 might be a tumor-specific feature of RCC, contributing to the tumorigenesis and tumor progression.

Prognostic Characteristics of MACC1 Expression in Epithelial Ovarian Cancer.

Recent studies have shown that overexpression of metastasis-associated in colon cancer 1 (MACC1) is significantly associated with adverse prognoses of patients with different kinds of cancer. However, the exact survival effect of MACC1 on epithelial ovarian cancer (EOC) patients has not yet been established. Thus, the objective of this study was to explore the prognostic role of MACC1 mRNA in EOC by using Kaplan-Meier (KM) plotter and ONCOMINE database. Our results indicated that MACC1 mRNA high expression was significantly associated with unfavorable overall survival (hazard ratio (HR) = 1.51 (95% confidence interval (CI): 1.21 - 1.88), P = 0.00025) and progression-free survival (HR = 1.53 (95% CI: 1.24 - 1.89), P = 5.8e-05) in EOC patients. We also found that the expression of MACC1 mRNA in EOC was 2.5 times higher than that in normal surface ovarian epithelium, which was statistically significant (P = 2.86e-7). Our results suggest that MACC1 expression might be a biomarker for poor prognosis in individual EOC patients.

Liquid biopsy prediction of axillary lymph node metastasis, cancer recurrence, and patient survival in breast cancer: A meta-analysis.

BACKGROUND: Liquid biopsies using circulating tumor DNA (ctDNA) and cell-free DNA (cfDNA) have been developed for early cancer detection and patient monitoring. To investigate the clinical usefulness of ctDNA aberrations and cfDNA levels in patients with breast cancer (BC), we conducted a meta-analysis of 69 published studies on 5736 patients with BC. METHODS: The relevant publications were identified by searching PubMed and Embase databases. The effect sizes of outcome parameters were pooled using a random-effects model. RESULTS: The ctDNA mutation rates of TP53, PIK3CA, and ESR1 were approximately 38%, 27%, and 32%, respectively. High levels of cfDNA were associated with BCs rather than with healthy controls. However, these detection rates were not satisfactory for BC screening. Although the precise mechanisms have been unknown, high cfDNA levels were significantly associated with axillary lymph node metastasis (odds ratio [OR] = 2.148, P = .030). The ctDNA mutations were significantly associated with cancer recurrence (OR = 3.793, P < .001), short disease-free survival (univariate hazard ratio [HR] = 5.180, P = .026; multivariate HR = 3.605, P = .001), and progression-free survival (HR = 1.311, P = .013) rates, and poor overall survival outcomes (HR = 2.425, P = .007). CONCLUSION: This meta-analysis demonstrates that ctDNA mutation status predicts disease recurrence and unfavorable survival outcomes, while cfDNA levels can be predictive of axillary lymph node metastasis in patients with BC.

Unique characteristics of ARID1A mutation and protein level in gastric and colorectal cancer: A meta-analysis.

BACKGROUND/AIM: Recently, AT-rich interactive domain-containing 1A protein (ARID1A) has been identified as a novel tumor suppressor gene in gastric cancer (GC) and colorectal cancer (CRC). However, the clinicopathologic value of ARID1A mutation or protein level in GC and CRC patients is controversial. Hence, we conducted a meta-analysis on the relationship between ARID1A aberrations and clinicopathologic parameters in GC and CRC. MATERIALS AND METHODS: Relevant published studies were selected from PubMed and EMBASE. The effect sizes of ARID1A mutation or level on the patient's clinicopathologic parameters were calculated by prevalence rate or odds ratio (OR) or hazard ratio (HR), respectively. The effect sizes were combined using a random-effects model. RESULTS: The frequency of ARID1A mutation and loss of ARID1A protein expression in GC patients was 17% and 27%, respectively. The loss of ARID1A protein expression of GC patients was significantly associated with advanced tumor depth (OR = 1.8, P = 0.004), lymph node metastasis (OR = 1.4, P = 0.001), and unfavorable adjusted overall survival (HR = 1.5, P < 0.001). ARID1A mutation of GC was significantly associated with microsatellite instability (MSI) (OR = 24.5, P < 0.001) and EBV infection (OR = 2.6, P = 0.001). The frequency of ARID1A mutation and ARID1A protein expression loss in CRC patients was approximately 12-13%. Interestingly, the loss of ARID1A protein expression in CRC patients was significantly associated with poorly differentiated grade (OR = 4.0, P < 0.001) and advanced tumor depth (OR = 1.8, P = 0.012). CONCLUSION: Our meta-analysis revealed that ARID1A alterations may be involved in the carcinogenesis of GC by EBV infection and MSI. The loss of ARID1A protein expression may be a marker of poor prognosis in GC and CRC patients.

[A case of IgG4 associated sclerosing cholangitis without clinical manifestations of autoimmune pancreatitis].

IgG4-related systemic diseases are characterized by a diffuse or mass forming inflammatory reaction rich in lymphocytes and IgG4-positive plasma cells (lymphoplasmacytic infiltration), fibrosclerosis of variable organs and obliterative phlebitis. They usually involve various organs including the pancreas, bile duct, gallbladder, salivary gland, retroperitoneum, kidney, lung, and prostate. However, most of them are accompanied by autoimmune pancreatitis, and good response to steroid treatment is one of the hallmarks of this disease. We report a case of an 67-year-old man with IgG4 associated sclerosing cholangitis, who was diagnosed by endoscopic retrograde cholangiopancreatography and successfully treated with steroid therapy.

Therapeutic strategies for well-differentiated papillary mesothelioma of the peritoneum.

OBJECTIVE: Well-differentiated papillary mesothelioma is an uncommon subtype of mesothelioma with a frequently indolent course, although it occasionally manifests in a more aggressive form. To establish a treatment strategy for this rare disease, we report the clinical characteristics and outcomes of 15 patients with well-differentiated papillary mesothelioma. METHODS: All pathologically diagnosed well-differentiated papillary mesothelioma cases were reviewed between 1998 and 2012. RESULTS: Of the 15 cases, 8 and 7 presented with single and multiple lesions, respectively. All cases with single lesions were asymptomatic, while 4 out of the 7 cases with multiple lesions were symptomatic. After tumor excision, none of the eight single-lesion cases experienced tumor recurrence. Among the other seven cases with multiple lesions, only one patient with disseminated lesions died due to disease burden. Five patients with multiple lesions received cisplatin-based intravenous or intraperitoneal chemotherapy, with a mix of complete (n= 2) and partial (n= 2) responses observed. Of particular note, one patient receiving cisplatin and pemetrexed combination chemotherapy experienced complete tumor resolution without any serious toxicity. CONCLUSIONS: We recommend different treatment strategies based on the disease status. If the tumor is completely resectable, an excisional biopsy seems to be sufficient. If complete resection is unavailable for the asymptomatic patient with a localized tumor extent, close follow-up is an appropriate option. When the tumor is extensive or accompanied by symptoms, chemotherapy should be strongly considered.

Human cutaneous protothecosis: report of a case and literature review.

The Prototheca species is achlorophyllic algae and rarely causes human infection. Human protothecosis presents clinically as a cutaneous infection, olecranon bursitis, and disseminated systemic disease. We report a case of human cutaneous protothecosis involving the left wrist. A 68-year-old man presented with an ill-defined erythematous lesion with crust at the dorsal aspect of his left wrist. A punch biopsy was performed to reveal the histologic features of granulomatous inflammation with necrosis at the upper dermis, containing Prototheca organisms, of which, the characteristic features were highlighted by special staining. Through a molecular study, the Prototheca zopfii species was identified.

A case of rheumatoid meningitis: pathologic and magnetic resonance imaging findings.

Central nervous system (CNS) involvement is extremely rare in patients with rheumatoid arthritis (RA). Additionally, most patients with CNS involvement have chronic and severe RA. We present a report of a 66-year-old man who was diagnosed with rheumatoid meningitis and CNS vasculitis without a history of RA. His initial symptom was seizure. Brain magnetic resonance imaging showed leptomeningeal enhancement.CSF analysis revealed slight increase in the number of white blood cells. An examination of viral markers and culture studies for infectious etiology were unremarkable. However, the rheumatoid factor was positive and the levels of anti-cyclic citrullinated peptide antibody were very high. The patient was diagnosed with rheumatoid meningitis and received steroid therapy. However, he developed CNS vasculitis. We suggested that the possibility of rheumatoid meningitis should be considered during the differential diagnosis stage in patients with uncontrolled meningitis, even though RA does not typically show CNS involvement.

Ultrasonography of normal and abnormal appendix in children.

Appendicitis is the most common acute surgical emergency of childhood. Since the original report by Puylaert in 1986, the use of ultrasonography in the diagnosis of appendicitis has been the subject of considerable study. Among the reported diagnostic criteria, the maximal outer diameter (MOD) of the appendix is accepted as the one of the most reliable criteria used to differentiate between a normal appendix and acute appendicitis. However, MOD measurement is subject to inaccuracies because luminal distention by non-compressible, non-inflammatory material such as fecal material, or increased maximal mural thickness due to reactive mucosal lymphoid hyperplasia, or a medical cause due to a generalized gastrointestinal disease, such as Crohn's disease, can cause the measurement to exceed the upper limits of normality. The aim of this article is to introduce the spectrum of ultrasonographic findings in the normal and abnormal appendix and eventually to reduce unnecessary surgery in children.

Behavioral changes as the earliest clinical manifestation of progressive supranuclear palsy.

BACKGROUND: The clinical and pathological heterogeneity of progressive supranuclear palsy (PSP) is well established. Even with a well-defined clinical phenotype and a thorough laboratory workup, PSP can be misdiagnosed, especially in its early stages. CASE REPORT: A 52-year-old woman, who we initially diagnosed with a behavioral variant of frontotemporal dementia developed parkinsonian features, which then progressed to gait instability and gaze abnormality. CONCLUSIONS: We report herein a pathologically confirmed case of PSP presenting with behavioral changes including agitation and irritability, which eventually led to the cardinal symptoms of progressive supranuclear palsy.

A case of basaloid follicular hamartoma.

Basaloid follicular hamartoma (BFH), uncommon rare benign neoplasm connected to the adnexal structures, presents with multiple clinical manifestations that can develop into basal cell carcinoma. BFH may be congenital or acquired, and the congenital form can be further divided into the generalized and unilateral type, and the acquired form may present as localized and solitary lesions. Congenital, generalized BFH is associated with systemic diseases such as alopecia, cystic fibrosis, hypohidrosis, and myasthenia gravis. In contrast, sporadic cases are observed as unilateral or localized lesions. BFH shows thick cords and thin strands of anastomosing basaloid proliferations that arise from hair follicles and are enclosed by loose fibrous stroma. Here, we report a 70-year-old man with an acquired, solitary form of BFH.

Eosinophilic gastroenteritis: a review.

Eosinophilic gastroenteritis is a clinicopathological disease affecting both children and adults that is characterized by patchy or diffuse eosinophilic infiltration of the gastrointestinal tract with variable resultant clinical gastrointestinal manifestations. The eosinophil, eotaxin, and Th-2 cytokines are important in pathogenesis of this disease entity. It may be confused with parasitic and bacterial infections (including Helicobacter pylori), inflammatory bowel disease, hypereosinophilic syndrome, myeloproliferative disorders, periarteritis, allergic vasculitis, scleroderma, drug injury, and drug hypersensivity. Obtaining the correct diagnosis is important, and a pathologist usually makes this distinction. Effective treatments include systemic/topical corticosteroids, specific food elimination or an elemental diet, certain drugs, and even surgery. A variety of new therapeutic approaches are now under trial.