Expression of Claudins in Preneoplastic Conditions of the Gastrointestinal Tract: A Review.

Premalignant lesions of the gastrointestinal tract are a group of disorders which act as the harbinger of malignant tumors. They are the ground-zero of neoplastic transformation, and their identification and management offer patients the best opportunity of blocking the progress of cancer. However, diagnoses of some of these conditions are hard to make, and their clinical importance is difficult to assess. Recent reports indicated that several claudin proteins have altered expressions in many cancers, including esophageal, gastric, colon, liver, and pancreatic cancers. The early identification of the aberrant expression of these proteins could lead to the early diagnosis and management of gastrointestinal tumors. Specifically, claudins -1, -2, -3, -4, and -18 are frequently overexpressed in gastrointestinal preneoplastic lesions. These altered expressions have shown clinical value in several tumors, providing diagnostic and prognostic information. In this article, we review the literature on the aberrant expression of claudins in preneoplastic lesions of the gastrointestinal tract. Additionally, we summarize their diagnostic and prognostic implications.

Original Article: MicroRNA Dysregulation in the Gastric Carcinogenesis Cascade: Can We Anticipate Its Role in Individualized Care?

BACKGROUND: Gastric carcinogenesis progresses from normal mucosa, atrophic/metaplastic gastritis, and dysplasia to adenocarcinoma. MicroRNAs (miRNAs) regulate DNA expression and have been implicated; however, their role is not fully established. AIMS: The aim of this study was to characterize plasma and tissue expression of several miRNAs in gastric carcinogenesis stages. METHODS: Single-center cross-sectional study in 64 patients: 19 controls (normal mucosa); 15 with extensive atrophic/metaplastic gastritis; and 30 with early gastric neoplasia (EGN). Seven miRNAs (miR-21, miR-146a, miR-181b, miR-370, miR-375, miR 181b, and miR-490) were quantified by real time-qPCR in peripheral blood and endoscopic biopsy samples. RESULTS: We found a significant upregulation of miR-181b, miR-490, and miR-21 in the EGN mucosa (overexpression 2-14-times higher than controls). We observed a significant underexpression of miR-146a and miR-370 in atrophic/metaplastic gastritis (86 and 66% decrease, p = 0.008 and p = 0.001) and in EGN (89 and 62% reduction, p = 0.034 and p = 0.032) compared with controls. There were no differences between lesions and nonneoplastic mucosa and no dysregulation of plasma miRNAs. CONCLUSION: We found significant dysregulation of 5 miRNAs in gastric carcinogenesis, suggesting a tumor suppressor role for miR-146a and miR-370 and oncogenic potential for miR-21, miR-181, and miR-490. These changes happen diffusely in the gastric mucosa, suggesting a high-risk field defect, which may influence these patients' surveillance.

Early detection and therapeutics.

Early detection, including cancer screening and surveillance, is emerging as one of the most important topics in modern oncology. Because symptomatic presentation remains the predominant route to cancer diagnosis, there is a growing interest in developing techniques to detect the disease at an early, curative stage. Moreover, growing understanding of cancer biology has paved the way for prevention studies with the focus on therapeutic interventions for premalignant conditions. Where there is a recognisable precursor stage, such as a colorectal adenoma or Barrett's metaplasia, the removal of abnormal tissue prevents the development of cancer and enables stratification of the patient to a high-risk group requiring further surveillance. Here, we provide a review of the available technologies for early diagnosis and minimally-invasive treatment.

Significance of HER2 and Ki-67 in Preneoplastic Lesions and Carcinoma of Gallbladder.

BACKGROUND: HER2 is an oncoprotein which is overexpressed in several cancers including breast and stomach. Several studies have shown that HER2 is overexpressed in gallbladder cancer and in precancerous lesions. The present study was undertaken to assess pattern and level of expression of HER2 in metaplasia, dysplasia, and different stages of gallbladder carcinoma, which would determine its suitability as a prognostic biomarker in neoplastic transformation of gallbladder epithelium. The study was also aimed at to find the significance of Ki-67 index in these lesions. METHODS AND MATERIALS: One hundred and twenty-eight patients who underwent cholecystectomy comprised the study group. Among them, 108 (84.4%) specimens showing metaplasia, dysplasia, and carcinoma on routine histopathology were considered as cases and 20 (15.6%) specimens of chronic cholecystitis having non-metaplastic mucosa were considered as control. Immunohistochemistry (IHC) was performed for HER2 and Ki-67. For HER2 interpretation ASCO/CAP guideline for breast cancer was followed. Chi-square test was used to find out the significance of HER2 expression in dysplasia/metaplasia/carcinoma. The ANOVA and Tukey-Kramer Multiple Comparisons Test were used for determining the association of Ki-67 with malignant transformation. RESULTS AND CONCLUSIONS: Overexpression of HER2 was observed in 48% (n = 12) of adenocarcinomas, 58% (n = 7) of high-grade dysplasia, 47% (n = 8) of low-grade dysplasia, and 74% (n = 25) of intestinal metaplasia. Ki-67 index increases in a non-linear fashion as the precursor lesions progress toward malignancy. In the future, these markers might be used as a prognostic biomarker for gallbladder carcinoma and its precursor lesions and it might become a valid indication for targeted therapies for gallbladder cancer.

Telomerase activity associated with progression of cervical lesions in a group of Colombian patients / Associação da atividade da telomerase com a progressão de lesões cervicais em um grupo de pacientes da Colômbia

Abstract PURPOSE To analyze the relation between the cytological findings and telomerase activity (TA). METHODS Cervical samples were evaluated and classified according to the Bethesda System. Telomerase activity was measured total product generated values (TPG) using the TRAP assay (telomeric repeat amplification protocol); data were analyzed statistically using the χ2 test, with the level of significance set at p<0.05. RESULTS The study was conducted on 102 patients. Of these, 3.9% showed normal cytological findings, 8.8% showed cervicitis; 2% showed Atypical Squamous Cells of Undetermined Significance (ASCUS); 67.6% showed Low Grade Squamous Intraepithelial Lesion (LSIL); 11.8% showed High Grade Squamous Intraepithelial Lesion (H-SIL) and 5.9% showed Squamous Carcinoma. Among telomerase-positive samples, the TPG values were cervicitis<normal<ASCUS<L-SIL<H-SIL<Carcinoma. CONCLUSION Results show increased telomerase activity with increasing severity of lesion, supporting the association between TA and type of lesion.

Resumo OBJETIVO Analisar a relação entre os achados citológicos e atividade da telomerase (AT). MÉTODOS Amostras cervicais foram avaliadas e classificadas pelo sistema Bethesda. A AT foi medida como valores de produto total gerado (PTG), utilizando o protocolo de amplificação repetida da telomerase (TRAP); os dados foram analisados estatisticamente usando o teste do χ2, com nível de significância de p<0,05. RESULTADOS Cento e dois pacientes foram analisados: 3,9% com achados citológicos normais, 8,8% com cervicite, 2% com células escamosas atípicas de significado indeterminado (ASCUS), 67,6% com lesão escamosa intraepitelial baixo grau (LEI-BG), 11,8 % com lesão intraepitelial escamosa alto grau (LEI-AG) e 5,9% com carcinoma escamoso. Valores PTG para amostras positivas AT foram: cervicite<normal<ASCUS<LEI-BG<LEI-AG<Carcinoma. CONCLUSÃO Os resultados mostram um aumento na AT com o aumento da lesão, sustentando a associação entre a AT e o tipo de lesão.

Helicobacter pylori and microRNAs: Relation with innate immunity and progression of preneoplastic conditions.

The accepted paradigm for intestinal-type gastric cancer pathogenesis is a multistep progression from chronic gastritis induced by Helicobacter pylori (H. pylori) to gastric atrophy, intestinal metaplasia, dysplasia and ultimately gastric cancer. The genetic and molecular mechanisms underlying disease progression are still not completely understood as only a fraction of colonized individuals ever develop neoplasia suggesting that bacterial, host and environmental factors are involved. MicroRNAs are noncoding RNAs that may influence H. pylori-related pathology through the regulation of the transcription and expression of various genes, playing an important role in inflammation, cell proliferation, apoptosis and differentiation. Indeed, H. pylori have been shown to modify microRNA expression in the gastric mucosa and microRNAs are involved in the immune host response to the bacteria and in the regulation of the inflammatory response. MicroRNAs have a key role in the regulation of inflammatory pathways and H. pylori may influence inflammation-mediated gastric carcinogenesis possibly through DNA methylation and epigenetic silencing of tumor suppressor microRNAs. Furthermore, microRNAs influenced by H. pylori also have been found to be involved in cell cycle regulation, apoptosis and epithelial-mesenchymal transition. Altogether, microRNAs seem to have an important role in the progression from gastritis to preneoplastic conditions and neoplastic lesions and since each microRNA can control the expression of hundreds to thousands of genes, knowledge of microRNAs target genes and their functions are of paramount importance. In this article we present a comprehensive review about the role of microRNAs in H. pylori gastric carcinogenesis, identifying the microRNAs downregulated and upregulated in the infection and clarifying their biological role in the link between immune host response, inflammation, DNA methylation and gastric carcinogenesis.

The expression of retinoblastoma tumor suppressor protein in oral cancers and precancers: A clinicopathological study.

BACKGROUND: The role of retinoblastoma (Rb) protein in cell cycle regulation prompted us to take up this study with the aim of assessing its role in the progression of oral cancer and to correlate with various clinicopathological parameters, including habits such as smoking, Paan chewing, and alcoholism. MATERIALS AND METHODS: This observational study included surgical specimens from 10 apparently normal oral mucosa, 14 oral reactive lesions (ORL), 29 precancerous lesions and 43 oral cancers. The expression of Rb protein in tissue samples were evaluated by immunohistochemistry and correlated with clinicopathological data. The percentage and mean expression of Rb protein were statistically analyzed using Student's t-test and P < 0.05 was considered as statistically significant difference. RESULTS: The expression of Rb protein was found to increase from normal, ORL, precancerous lesions to cancers. A consistently high expression of Rb protein was seen in oral cancers, with an increase in well-differentiated and moderately differentiated tumors. Patients with combined habits of Paan chewing, smoking, and alcohol consumption had a higher expression compared with those without habits. CONCLUSION: Within the limitations of this study, it seems that overexpression of Rb protein noted in oral cancer, with an increase in well and moderately differentiated tumors suggest a possible role of Rb in differentiation. The high expression of Rb in patients with combined habits of Paan chewing, smoking and alcohol consumption indicates that Rb pathway may be altered in habit-related oral malignancies.

In Situ Follicular Lymphoma Developed after Hodgkin Lymphoma

In situ follicular lymphoma is a newly defined entity among the lymphoid neoplasms and is defined as architecturally normal-appearing lymph nodes and other lymphoid tissues that have one or more follicles that demonstrate bcl-2 overexpressing centrocytes and centroblasts, with or without a monomorphic cytologic appearance suggestive of follicular lymphoma. Here we present a case of in situ follicular lymphoma diagnosed during the follow-up after a complete response to the treatment of lymphocyte-rich classical Hodgkin's lymphoma. In our case, because only a few germinal centers contained bcl-2 overexpressing cells, we missed the diagnosis of in situ follicular lymphoma in the initial histological examination. We could establish the diagnosis only after performing bcl-2 immunostaining in the sequential biopsy. Therefore, we recommend that careful histological examination along with bcl-2 immunostaining is needed in patients with suspicious clinical findings.

CO2 Laser Resurfacing in Skin Tumor Surgery

PURPOSE: The prevalence of skin cancers and cutaneous premalignant lesions are increasing recently. It is necessary to treat cutaneous premalignant lesions, because these can progress to invasive skin cancers. We conducted a retrospective study to evaluate the usefulness of CO2 laser resurfacing in skin tumor surgery. METHODS: From 2005 to 2008, 14 patients with skin cancers, photodamaged skin and cutaneous premalignant lesions were treated with skin cancer excision, immediate reconstruction, and CO2 facial laser resurfacing. Mean average follow-up period was 15.6 months(5 months-36 months). Biopsy and clinical photograph were taken preoperatively, intraoperatively and through follow-up period to assess the effectiveness of laser resurfacing. Recurrence and side effects were evaluated through follow-up period. RESULTS: Histologic examination shows the abolition of actinic atypia, regeneration of epidermis and normalization of cellular differentiation after laser resurfacing. Clinical photographs shows elimination of keratoses and spots, and the homogeneous, smoothening change of skin surface, indicating healthy and younger faces. All patients had remained free of skin cancers and premalignant lesions in laser-treated field through follow-up period. CONCLUSION: CO2 laser resurfacing in skin tumor surgery can treat not only premalignant lesions but also subclinical lesions of photodamaged skin. Moreover it may be helpful in prophylaxis against skin cancers and premalignant lesions, providing rejuvenation and cosmetic improvement.