Non-computer-assisted liquid-based cytology for diagnosis of oral squamous cell carcinoma

Abstract

The development of oral squamous cell carcinoma (OSCC) occasionally follows the neoplastic progression of other premalignant lesions. Although biopsy is the definitive diagnostic method, liquid-based cytology is an adequate method for screening suspicious lesions. We compared liquid-based cytology to histology for diagnosis of OSCC in patients with oral lesions that raised clinical suspicion of malignancy. Our sample consisted of 48 patients. Cytological samples were obtained by scraping the lesion superficially using Cytobrush^®. We conducted cytological and histopathological evaluation of all preparations. We estimated sensitivity and specificity levels as well as positive and negative predictive values. The degree of inter-observer agreement for both methods was assessed using the kappa index. Twenty-eight (58.3%) of the cases finally were diagnosed with OSCC and 20 (41.7%) were determined to be premalignant lesions. We observed eight false negatives and no false positives; OSCC prevalence was 56.5%. The values for diagnostic indices were: sensitivity, 69% (CI 95%, prevalence 51.87); specificity, 100%; positive predictive value, 100%; negative predictive value, 71% (CI 95% 54.82). A kappa index of 0.622 (CI 95% 0.93, 0.39) was observed.     

New potential biomarkers in the diagnosis of esophageal squamous cell carcinoma

Objective: To analyse the alterations of serum proteins in cases of esophageal squamous cell carcinoma (ESCC) in order to screen and validate serum marker patterns for the diagnosis of ESCC in the high-risk populations of Xinjiang, China. Methods: The serum proteomic patterns of 188 cases, including 139 patients with ESCC (54 Uygur, 45 Kazakh and 40 Han subjects) and 49 sex- and age-matched healthy controls, were detected using the SELDI-TOF-MS (surface-enhanced laser desorption/ionization–time of flight–mass spectrometry) technology with the CM10 ProteinChip. Differences in protein peaks between patients with ESCC and controls were analysed using the Biomarker Pattern Software, and a primary diagnosis model of ESCC was developed and validated with SVM (support vector machines). This model was further evaluated by a large-scale blind test. Results: Two hundred and eighty-three protein peaks were detected within the molecular range of 0–20?kDa, among which, 140 peaks were significantly different between ESCC cases and controls (p?m/z 5667, 5709, 5876, 5979, 6043 and 6102) was established with a sensitivity of 97.12% and a specificity of 83.87%. The large-scale blind test generated a sensitivity of 91.43% and a specificity of 88.89%. Conclusions: The differential protein peaks analysed by SELDI-TOF-MS may contain promising serum biomarkers for screening ESCC. The diagnostic model which combined only six protein peaks had a satisfactory discriminatory power. The model should be further evaluated in other populations of ESCC patients and tested against controls. The nature and function of the discriminating proteins have yet to be elucidated.     

食管鳞癌染色体及基因组DNA畸变研究进展

食管鳞癌是我国常见的消化道恶性肿瘤,进展快且预后差。由于早期一般无明显症状,临床确诊的食管鳞癌大多已发展到了中晚期,治愈难度较大。越来越多的证据表明,在食管鳞癌发生发展过程中,染色体及基因组DNA畸变均是最常见的遗传学改变。文章就食管鳞癌染色体及基因组水平异常的研究进展作一综述。     

食管鳞癌染色体及基因组DNA畸变研究进展

食管鳞癌是我国常见的消化道恶性肿瘤, 进展快且预后差。由于早期一般无明显症状, 临床确诊的食管鳞癌大多已发展到了中晚期, 治愈难度较大。越来越多的证据表明, 在食管鳞癌发生发展过程中, 染色体及基因组DNA畸变均是最常见的遗传学改变。文章就食管鳞癌染色体及基因组水平异常的研究进展作一综述。     

Fine needle aspiration cytology of squamous cell carcinoma of the breast

A rare case of pure squamous cell carcinoma of the breast is reported in which the diagnosis was initially suggested by fine needle aspiration cytology. Smears and cell blocks of the aspirate showed atypical keratinized cells admixed with inflammatory cells. The diagnosis was confirmed by open biopsy. The excised tumor tissue was positive for both estrogen and progesterone receptors; flow cytometry showed a diploid DNA content and a high S-phase fraction.     

Serum metabolomics for early diagnosis of esophageal squamous cell carcinoma by UHPLC-QTOF/MS

Introduction

Previous metabolomics studies have revealed perturbed metabolic signatures in esophageal squamous cell carcinoma (ESCC) patients, however, most of these studies included mainly late-staged ESCC patients due to the difficulties of collecting the early-staged samples from asymptotic ESCC subjects.

Objectives

This study aims to explore the early-staged ESCC metabolic signatures and potential of serum metabolomics to diagnose ESCC at early stages.

Methods

Serum samples of 97 ESCC patients (stage 0, 39 cases; stage I, 17 cases; stage II, 11 cases, stage III, 30 cases) and 105 healthy controls (HC) were enrolled and randomly separated into training data (77 ESCCs, 84 HCs) and validation data (20 ESCCs, 21 HCs). Untargeted metabolomics was performed to identify ESCC-related metabolic signatures.

Results

The global metabolomics profiles could clearly distinguish ESCC from HC in training data. 16 ascertained metabolites were found to be disturbed in the metabolic pathways characterized by dysregulated fatty acid biosynthesis, glycerophospholipid metabolism, choline metabolism in cancer and linoleic acid metabolism. The AUC value in validation data was 0.895, with sensitivity 85.0 % and specificity 90.5 %. Good diagnostic performances were also achieved for early stage ESCC, with the values of area under the curve (AUC) 0.881 for the ESCC patients in both stage 0 and I–II. In addition, six metabolites were found to discriminate ESCC stages. Among them, three biomarkers, dodecanoic acid, LysoPA(18:1), and LysoPC(14:0), exhibited clear trend for ESCC progression.

Conclusion

These findings suggest serum metabolomics, performed in a minimally noninvasive and convenient manner, may possess great potential for early diagnosis of ESCC patients.

     

Genes responsible for etiopathogenesis in esophageal squamous cell carcinoma

Esophageal squamous cell carcinoma is a very important cancer type, not only because of its frequent cases around the world but also because of its high mortality rate. Despite of the fact that this is a very rare cancer in Poland (around 2% of patients), we need to know more about this disease in order to find better ways to fight it. Epidemiological factors: smoking and use of psychoactive substances like alcohol and drugs, poor diet as well as changes in expression of genes may have influence on this cancer. During last years there has been a lot of researche on the role of GEAC1, which seems to play a very important role in normal and cancer cells. Perhaps the protein coded by this gene is an important part in cancer development, also being an important element in processes in normal tissues.     

Fine needle aspiration biopsy cytology of metastatic renal cell carcinoma

Sixteen cases of metastatic renal cell carcinoma diagnosed by fine needle aspiration biopsy were reviewed. Polygonal malignant epithelial cells present in sheets with loose or strong cellular cohesiveness and granular, vacuolated or filmy cytoplasm were the characteristic findings of this type of tumor.     

MicroRNA-25 promotes cell migration and invasion in esophageal squamous cell carcinoma

MicroRNAs (miRNAs) as a species of small non coding single stranded RNA of about 21-25 nucleotides have important roles in the development of different cancers. In present study, we found that the expression of miR-25 was up-regulated in 60 esophageal squamous cell carcinoma (ESCC) tissues compared with matched adjacent non-cancer tissues. Moreover, we demonstrated that the up-regulation of miR-25 was significantly correlated with the status of lymph node metastasis and TNM (Tumor, Node and Metastasis) stage. Furthermore, over-expression of miR-25 markedly promoted migration and invasion of ESCC cells. On the contrary, down-regulation of miR-25 inhibited the migration and invasion of cells. E-cadherin(CDH1) is a very important tumor metastasis suppressor. We further identified that miR-25 directly targeted CDH1 3'-untranslated region (3'UTR) and repressed the expression of CDH1. These results, for the first time, demonstrate that miR-25 promotes ESCC cell migration and invasion by suppressing CDH1 expression.     

Altered expression of ezrin in esophageal squamous cell carcinoma.

Ezrin is a membrane-cytoskeletal linker belonging to the ezrin-radixin-moesin (ERM) family and has been suggested to be involved in tumorigenesis. In this study we investigated ezrin expression pattern in normal esophageal mucosa and esophageal squamous cell carcinoma (ESCC) and the correlation with clinical characteristics. Immunohistochemical staining showed a tendency for ezrin to translocate from membrane to cytoplasm in the progression from normal epithelium to invasive carcinoma of the esophagus. By Western blot, we found that ezrin expression was downregulated in 13 ESCC specimens and upregulated in 36 others. Moreover, quantitative real-time RT-PCR demonstrated that ezrin mRNA level in normal esophageal mucosa was 3.60 +/- 3.60 times that in ESCC (p<0.001). Proliferating cell nuclear antigen (PCNA) expression level was higher in ezrin downregulated group compared with that in ezrin upregulated group (p<0.05). However, there was no significant association between ezrin expression and clinical characteristics. The results suggested that the localization of ezrin by immunohistochemistry may be useful in the diagnosis of ESCC, and ezrin may play a suppressive role in the tumorgenesis of ESCC.     

Immunoexpression of nm23 in advanced esophageal squamous cell carcinoma

The study was undertaken to determine the immunoexpression of protein products of nm23 genes which are thought to be potential metastasis suppressor genes, in esophageal squamous cell carcinoma, and to analyze their relationship to selected clinicopathological features (age, sex, tumour size, depth of invasion, presence of lymph nodes and distant metastasis, pathologic tumor stage, degree of cancer differentiation and vascular/lymphatic invasion), as well as to the overall survival. Immunohistochemical staining with monoclonal antibody against nm23 using LSAB2/HRP method on formalin-fixed, paraffin-embedded sections obtained from 32 tumors was performed. Eight tumors (25%) showed positive nm23 immunoexpression. There were no statistically significant differences between nm23-positive and nm23-negative groups with respect to all clinicopathological features studied. The positive nm23 status was related to a worse prognosis but this was not significant. The results may suggest that nm23-status is not associated with metastatic ability and prognosis in esophageal squamous cell carcinoma, but such thesis requires further study on a larger population.     

Over-expression of Oct4 in human esophageal squamous cell carcinoma

The Octamer 4 gene (Oct4) is a master pluripotency controller that has been detected in several types of tumors. Here, we examine the expression of Oct4 in human esophageal squamous cell carcinoma (ESCC). We found that punctate Oct4 protein was expressed in most (93.7%) ESCC samples but it was not observed in esophageal mucosa. Some ESCC cells had the capacity to form tumorospheres; those with an Oct4⁺-rich cell phenotype had increased proliferation and Oct4 mRNA levels compared to those of differentiated cells in culture or xenograft tumors. The over-expression of Oct4 in ESCCs suggests that it is a potential target for ESCC therapy. Oct4 could be a useful tumor marker in an immunohistochemical panel designed to differentiate between ESCC and esophageal mucosa. Expression of Oct4 in tumorospheres might indicate the presence of a population of ECSCs and its expression in xenograft tumors suggests that Oct4 is also associated with tumor metastasis.     

Endoscopic cytology and biopsy in the diagnosis of gastroesophageal malignancy

Direct-vision endoscopic cytologies and biopsies were performed on 1,437 patients during a five-year period, and the incidence, correct typing and diagnosis of gastroesophageal cancer were studied. At the first cytology, malignant cells were diagnosed in 80 cases, all of which were confirmed by the endoscopic biopsy; in 30 cases, despite suspicious cytology, no malignancy was seen at the first biopsy. At repeat endoscopic cytology and biopsy, however, 21 of these 30 cases were correctly correlated for malignancy, resulting in a final correct correlation in 101 of the 110 cases (91.8%) and a diagnostic discrepancy in 9 cases (8.2%). It thus appears that the procedure is useful in diagnosing gastroesophageal cancer in the majority of cases. In the cases of discrepancies, gastric ulcers were found later; the repeatedly suspicious cytologies were due to the cytologic atypia of the cells from regenerating hyperplastic and/or metaplastic epithelium at the margins of the ulcers. Such cells showed a wide spectrum of changes, ranging from mild atypia to severe atypia mimicking adenocarcinoma of the upper gastrointestinal tract.     

The impact of liquid-based oral cytology on the diagnosis of oral squamous dysplasia and carcinoma

OBJECTIVE: Even though diagnostic oral exfoliative cytology is a useful, economical and practical tool in the diagnosis of oral dysplasia and carcinoma, it is not yet extensively used. The results of conventional exfoliative and liquid-based diagnostic cytology in oral potentially malignant lesions (PML) are herein reported and compared with the histological diagnosis. METHODS: Either conventional (89) or liquid-based (384) exfoliative cytology was used for the diagnosis of oral dysplasia/carcinoma in 473 subjects and the results were compared with scalpel biopsy histology. Cells were collected using a Cytobrush device for conventional smears and with a dermatological curette for the liquid-based cytology. The 'curette technique' also allowed for the collection of 'accidental' tissue fragments, utilized as microbiopsies. RESULTS: Histological diagnosis was squamous carcinoma in 96 of 473 cases, high-grade dysplasia (oral intraepithelial neoplasia two to three) in 24 and other lesions in 353 cases. The smears in the conventional cytology group were inadequate in 12.4%, with an 85.7% sensitivity and a 95.9% specificity. There were 8.8% of inadequate specimens in the liquid-based cytology group; sensitivity was 95.1% and specificity was 99.0%. CONCLUSIONS: Although conventional cytology is useful when diagnosing oral PML (better sensitivity and predictive positive value if compared with the cervical smear test with similar specificity) and can improve the accuracy of histological diagnosis, liquid-based cytology gives better results, as it not only enhances both sensitivity and specificity, but also provides material for further investigation (AgNORs, DNA, microbiopsies, etc.).     

NOB1在食管鳞状细胞癌中的表达及临床意义

目的研究NOB1基因在食管鳞状细胞癌（Esophageal squamous cell carcinoma,ESCC）中的表达及临床意义。方法利用免疫组织化学SP法检测59例ESCC及其相应（50例）的远端正常食管黏膜组织中NOB1的表达。结果 ESCC中NOB1的阳性率为71%,正常食管黏膜鳞状上皮中的阳性率为26%,两组比较,差异有统计学意义（P〈0.05）。NOB1的表达与ESCC的分化程度及淋巴结转移相关,与患者的性别,年龄以及肿瘤浸润深度无关。结论 NOB1在ESCC中表达升高,可能在ESCC发生发展过程中起重要作用。