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Aims: Despite clinical evidence of liver involvement in patients with coeliac disease (CeD), there is a lack of a method to prove this association., Methods: Of 146 treatment-naive patients with CeD, 26 had liver dysfunction. Liver biopsies and corresponding small intestinal biopsies were obtained from these 26 patients. Multicolour immunohistochemical and immunofluorescence confocal microscopic studies were performed on paraffin-embedded tissue to detect the IgA/anti-TG2 deposits. Follow-up liver biopsies were taken after a gluten-free diet., Results: Twenty-six out of the 146 patients (17.8%) with suspected coeliac-associated liver disease on histological examination revealed irregular sinusoidal dilatation in 15 (57.6%), steatohepatitis in 4 (15.3%), non-specific chronic hepatitis in 3 (11.5%), autoimmune hepatitis in 2 (7.6%) biopsies, including cirrhosis in one of them, irregular perisinusoidal fibrosis and changes of non-cirrhotic portal fibrosis in one biopsy each (3.8%). IgA/anti-tTG deposits were observed in 22 (84.6%) liver biopsies by dual immunohistochemistry technique, and in 24 (92.3%) by confocal immunofluorescence technique and in all corresponding duodenal biopsies (100%). Overall, IgA/anti-tTG deposits showed 100% sensitivity, 77% specificity and 85% positive predictive value for establishing an association of extraintestinal pathology and CeD using archived tissues. Follow-up liver biopsies could be obtained in five patients; four of them showed not only resolution of the histological lesions but disappearance of IgA/anti-tTG co-localisation., Conclusions: Data of the present study adds to the body of evidence that liver lesions in patients with CeD are disease related and may have been caused by a similar pathogenic mechanism that causes intestinal changes., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Breast carcinoma shows amplification/overexpression of Her-2/neu in ∼20-30% of cases. The determination of Her-2/neu expression accurately is vital in clinical practice as it has significant predictive value and eligibility for anti Her-2/neu therapy. Amplification and overexpression of Her-2/neu gene is traditionally identified by fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC) on tissue sections; only a few studies have evaluated feasibility of these techniques on cytological smears. One hundred cases of breast cancer with fine-needle aspiration cytology (FNAC) samples and corresponding surgically resected specimen were selected. Immunocytochemistry (ICC) and FISH for Her-2/neu was done on FNA smears, whereas IHC was performed on corresponding tissue sections. Diagnostic accuracy of ICC was 99% when compared with IHC. Comparison of FISH results with IHC showed 100% concordance. Unlike many centers in West, FNAC is still routinely performed in developing countries like India where vast majority of breast cancer cases present as palpable lumps. The high rates of accuracy of ICC and FISH for Her-2/neu detection can make FNAC a relevant first line of investigation as a cost effective model with a rapid turn-around time, providing complete information necessary for initial management of breast cancer patients., (Copyright © 2013 Wiley Periodicals, Inc.)

Objective: This study focused on whether primary cultures of ovarian cancer (OC) cells established from ascites can be used to evaluate response to chemotherapeutic agents and if curcumin could enhance the efficacy of these agents.Materials and Methods: We established five primary cultures of ascitic cells from OC patients and treated them with curcumin, carboplatin, and paclitaxel singly and in combinations. The percentage of apoptotic cells was determined by flow cytometry.Results: There was a wide variation in the response of individual primary cultures to treatment with the chemotherapeutic agents. Curcumin by itself was as good as carboplatin or paclitaxel in inducing apoptosis in the primary OC cells. Curcumin was not able to affect the carboplatin mediated cell killing. However, a combination of curcumin and paclitaxel was additive and was equally effective as a combination of carboplatin and paclitaxel. A combination of curcumin carboplatin, and paclitaxel was also found to be additive and, in fact, turned out to be the best combination that gave the highest percentage of apoptosis in vitro.Conclusion: This study highlights the fact that primary cultures of OC cells can be used to detect response to chemotherapeutic agents and help to individualize the treatment offered to OC patients. [ABSTRACT FROM AUTHOR]

Purpose: Role of (18 [F] fluorine-18-labeled 2-fluoro-2-deoxy-D-glucose [FDG] positron emission tomography-computed tomography [PET-CT]) in the evaluation of axillary lymph node involvement in T1T2N0 breast cancer and compare results with sentinel lymph node biopsy (SLNB). Methods: A total of 37 patients of proven T1T2N0 breast cancer were included in the study. Patients with past history of breast surgery, T3T4 disease, uncontrolled diabetes mellitus and pregnant patients were excluded from the study. Pre-operative FDG PET-CT was performed followed by sentinel lymph node (SLN) biopsy with blue dye or combined technique. Results: SLN was identified in 32 of 37 patients with an identification rate of 86.48% (32/37). With combined technique SLN identification rate was 100% (6/6) while with blue dye alone; it was 83.8% (26/31). Among 37 patients, 16 had axillary metastases of which 12 had macrometastases and four had micrometastases detected by immunohistochemistry (IHC). Of 12 patients with axillary macrometastases, skip metastases were present in two patients in whom SLN was negative and in two patients SLN was not identified, but axillary dissection showed metastases. PET-CT had shown sensitivity, specificity, negative predictive value and positive predictive value of 56%, 90%, 73%, and 81.8%, respectively. IHC of SLN detected four patients with micrometastases upstaging the disease by 11% (4/37). Conclusion: Because FDG PET-CT has a high specificity in the evaluation of axillary lymph node involvement in T1T2N0 breast cancer patients according to the results of this study if FDG PET-CT is positive in axillary lymph nodes, axillary lymph node dissection may be considered instead of SLNB. [ABSTRACT FROM AUTHOR]

Background: The functional and clinical significance of 14-3-3 proteins in human cancers remain largely undetermined. Earlier, we have reported differential expression of 14-3-3ζ mRNA in oral squamous cell carcinoma (OSCC) by differential display. Methods: The clinical relevance of 14-3-3ζ protein in oral tumorigenesis was determined by immunohistochemistry in paraffin embedded sections of oral pre-malignant lesions (OPLs), OSCCs and histologically normal oral tissues and corroborated by Western Blotting. Co-immunoprecipitation assays were carried out to determine its association with NFκB, β-catenin and Bcl-2. Results: Intense immunostaining of 14-3-3ζ protein was observed in 61/89 (69%) OPLs and 95/ 120 (79%) OSCCs. Immunohistochemistry showed significant increase in expression of 14-3-3ζ protein from normal mucosa to OPLs to OSCCs (Ptrend < 0.001). Significant increase in expression of 14-3-3ζ protein was observed as early as in hyperplasia (p = 0.009), with further elevation in moderate and severe dysplasia, that was sustained in OSCCs. These findings were validated by Western blotting. Using Co-immunoprecipitation, we demonstrated that 14-3-3ζ protein binds to NFκB, β-catenin and Bcl-2, suggesting its involvement in cellular signaling, leading to proliferation of oral cancer cells. Conclusion: Our findings suggest that over-expression of 14-3-3ζ is an early event in oral tumorigenesis and may have an important role in its development and progression. Thus, 14-3-3ζ may serve as an important molecular target for designing novel therapy for oral cancer. [ABSTRACT FROM AUTHOR]

Objective: TheMEMD gene was reported to be overexpressed in human esophageal squamous cell carcinoma (ESCC), using differential display. The aim of this study was to determine the clinical significance of MEMD/ALCAM in esophageal tumorigenesis. Methods: Analysis of MEMD/ALCAM expression in esophageal tissues was carried out at protein and RNA level using immunohistochemistry and semiquantitative RT-PCR, respectively. Results: Increased MEMD/ALCAM expression was observed in 42/65 (65%) ESCCs (p = 0.000, odds ratio, OR = 3.665) and in 17/25 (68%) dysplasias (p = 0.000, OR = 4.248) compared to paired distant histologically normal esophageal tissues. Increased MEMD mRNAlevels were observed in ESCCs and dysplasias showing overexpression of MEMD/ALCAM protein. Interestingly, increased membranous MEMD/ALCAM expression was observed in dysplasias in comparison with ESCCs (p = 0.002, OR = 3.177). MEMD/ALCAM overexpression in ESCCs was associated with late clinical stage (p = 0.002, OR = 3.619), enhanced tumor invasiveness (p = 0.002, OR = 3.619), and nodal metastasis (p = 0.000, OR = 4.206). Conclusion: To our knowledge, this is the first report showing MEMD expression at pre-malignant stage (dysplasia), suggesting that MEMD/ALCAM expression is an early event in the development of esophageal cancer. Furthermore, in ESCCs its correlation with late clinical stage, enhanced tumor invasiveness and nodal metastasis suggests an association with aggressive tumor behavior. Our data suggest that MEMD/ALCAM may serve as a potential marker for early diagnosis, tumor invasion and nodal metastasis in ESCCs. Copyright © 2005 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Objective To examine Juvenile Angiofibroma (JA) tissue for expression of vascular endothelial growth factor (VEGF), and to explore its relationship with puberty status, stage, recurrence and the intraoperative blood loss. Methods Retrospective cohort study of 36 histologically proven cases of JA. Minimum follow up period was 3 years. VEGF expression on tumor cells assessed by immunohistochemistry and graded on two criteria – percentage of cells expressing positivity and the intensity of positivity. These two parameters assessed for impact on puberty status, stage, recurrence, and blood loss. Results VEGF expression noted on the tumor endothelial cells in 36/36, and on the tumor stromal cells in 34/36. The percentage of cells expressing VEGF and the intensity of expression were not significantly related to puberty status, tumor stage, recurrence, or intra-operative blood loss ( p values 0.3–1.0). Conclusion VEGF expression is near universal in JA. Such expression is independent of puberty status and stage, and does not impact on intra operative blood loss and recurrence. [ABSTRACT FROM AUTHOR]

Background Histological assessment of dysplasia in Barrett’s esophagus (BE) has high inter-observer variability. Hence, use of ancillary markers for early detection of dysplasia in BE is an important clinical question. Methods In this retrospective study consecutive cases of BE (n = 59), over a period of 4 years were included. Hematoxylin and eosin stained sections were reviewed independently by 3 senior qualified pathologists, who graded the dysplasia according to the Vienna Classification system and inter-observer agreement was analysed using the Kappa statistics. Subsequently Alpha-Methyl Acyl-CoA Racemase (AMACR), p53, CyclinD1, β-catenin, H2AX and M30 immunohistochemical (IHC) stains were examined on the following disease categories: BE with no dysplasia [NFD] (45), BE with indefinite for dysplasia (IFD) (4), low grade dysplasia (LGD) (3), high grade dysplasia (HGD) (2) and in adenocarcinomas (5). H score was calculated by adding up products of different grades of stain distribution and stain intensities (range of scores 0–300). Results Among the 3 pathologists, overall agreement was poor (k 0.06; 95% CI −0.089 to 0.145), with highest disagreement noted for differentiating the LGD and IFDs (k = 0.21). After revising the histological criteria, the kappa improved to 0.53. Among the IHC stains performed, p53, β-catenin, H2AX and M30 stains were significantly useful to differentiate between IFD and LGD ( P values: 0.04, 0.004, 0.05 & 0.04, respectively). AMACR and β-catenin stains though were up-regulated in HGD/adenocarcinomas than in other categories, their expression were not statistically different between the IFD and LGDs. Conclusions A detail histological scoring system may bring uniformity in histological interpretation of dysplasia in BE. Using a combined panel of IHC stains seems helpful in detection of dysplasia in BE, especially to differentiate the IFD and LGD changes in BE. [ABSTRACT FROM AUTHOR]

Context.--The data on status of apoptosis in patients with celiac disease are conflicting. Furthermore, complex interaction between intrinsic and common apoptotic pathways, apoptotic inhibitors, and epithelial cell proliferation is largely unclear for patients with celiac disease. Objectives.--To determine the role of apoptosis and epithelial cell regeneration in celiac disease. Design.--Twenty-five treatment-naïve patients with celiac disease and 6 patients with functional dyspepsia, as controls, were included and duodenal biopsy specimens from all were subjected to immunohistochemistry with markers of intrinsic apoptotic pathway (AIF, H2AX, p53), common pathway (CC3, M30), apoptotic inhibitors (XIAP, Bcl2), and epithelial proliferation (Ki-67). Apoptotic and proliferation indices were calculated. Results.--Expression of end-apoptotic products, that is, H2AX in the cell nuclei (P = .01) and M30 in the cell cytoplasm (P < .01), was significantly upregulated in celiac disease in comparison to controls. Cleaved caspase- 3 was also upregulated in villous cytoplasm in celiac disease. Apoptotic inhibitor Bcl2 was significantly downregulated in celiac disease in comparison to controls. In addition, Ki-67 proliferation index was upregulated both in the crypts and villous mucosal epithelium in comparison to the crypts of the controls. Conclusions.--Treatment-naïve patients with celiac disease have significantly higher level of apoptosis that involves both the common and intrinsic apoptotic pathways. Increased apoptosis and unequaled cell regeneration in crypts probably results in villous atrophy. Downregulation of apoptotic inhibitors in treatment-naïve celiac disease imparts an additional pro-apoptotic effect. [ABSTRACT FROM AUTHOR]