Systematic assessment of HER2/neu in gynecologic neoplasms, an institutional experience.

BackgroundHER2/neu overexpression and/or amplification has been widely studied in a number of solid tumors, primarily in the breast. In gynecologic neoplasms, determination of HER2/neu status has not been well studied as a predictive biomarker in anti-HER2/neu treatment.MethodsWe systematically evaluated the HER2/neu reactions by immunohistochemistry and fluorescent in situ hybridization in malignant gynecologic neoplasms as experienced in our institution.ResultsThe HER2/neu overexpression or amplification occurred in 8 % of the cancers of the gynecological organs in our series. Majority of the HER2/neu overexpression and/or amplification occurred in clear cell (27 %) and serous (11 %) carcinomas. HER2/neu positivity was also seen in undifferentiated as well as in mixed clear cell and serous carcinomas. Discordant IHC and FISH results (positive by FISH but not IHC) was seen in 2 cases. Majority of the HER2/neu overexpression and/or amplification occurs in the endometrium rather than the ovary. Heterogeneity of the HER2/neu by IHC staining was in < 2 % of the tumors in our series.ConclusionsWe recommend the HER2/neu studies on Müllerian carcinomas of clear cell, serous, and undifferentiated types, particularly when they arise in the endometrium. Since there are some discordant IHC/FISH results, we also propose performing the HER2/neu testing by FISH when the IHC score is less than 3 + 

Interleukin 6 (IL6) as a predictor outcome in patients with compensated cirrhosis and symptomatic gall stones after cholecystectomy

Compensated cirrhosis means that the liver is heavily scarred but can still perform many important functions; many peoples with compensated cirrhosis have gall bladder stones. The advantages of laparoscopic cholecystectomy (LC) for most patients have been extensively published. However its benefits and successful use in patients with cirrhosis are less documented. The study compromised 50 patients with symptomatic gallstone in compensated liver disease and undergone either open cholecystectomy (OC) or laparoscopic cholecystectomy. These patients were randomized into two groups: Group I included 24 patients who underwent OC, and group II included 26 patients who underwent LC. Patient’s age, sex, clinical presentation and Child-Turcotte-Pugh (CTP) class were documented. No patients in this study had CTP class c cirrhosis. IL-6 was measured by ELISA, postoperative pain (measured by Visual analog scale), hospital stay, blood loss, recovery time (return to work), and liver function tests were documented. IL-6 was significantly lowered at 6th hour and 12th hour post operative in LC group. Mean surgical time was significantly longer in OC than LC group, (mean ±SD, 96.6 ±32 vs 58.7 ± 23.8 min, P = 0.037). No patients in group II required any blood replacement in contrast to 9 patients (37.5%) in group I. Intraoperative bleeding remained significantly higher in group I (P = 0.043). No patients in group II had wound complications compared with 5 patients (29.14%) in group I. Group I had significantly longer hospital stay than group II, mean 9.0+ 1.3 days (median 7) vs 2.3 days + 1.9 (median 2.5); P = 0.001. Our results were demonstrated that laparoscopic cholecystectomy can be performed safely in patients with CTP class A and B cirrhosis. IL-6 was more significantly, increased post operatively in open cholecystectomy than laparoscopic one and it correlated well with intensity of operative trauma. Keywords: Interleukin 6; Liver cirrhosis; Cholecystectom

Development and validation of spectrofluorimetric method for determination of diflunisal and its impurity

A new sensitive, simple, rapid, accurate and precise spectrofluorimetric method for determination of diflunisal and its impurity is developed. Determination of diflunisal is based on first derivative spectrofluorimetric method, while its impurity can be determined by zero order spectrofluorimetric method. Diflunisal was measured at zero-crossing wavelength 394nm (zero crossing point with its impurity) which was selected for quantification of diflunisal. The impurity was measured directly at 334 nm, using 0.05 M phosphate buffer (pH = 9) as solvent. The analytical signal resulting from first derivative and zero order spectra were measured for diflunisal and its impurity, respectively. Linearity was over the range of 0.1-0.9 μg/mL for both with detection limit of 0.02 and 0.03 μg/mL and quantitation limit of 0.07 and 0.09 μg/mL for diflunisal and its impurity, respectively. The proposed method was validated as per ICH guidelines.The accuracy was checked by applying the proposed method for the determination of the drug and its impurity, the mean percentage recoveries were found to be 99.61±0.911 and 100.41±1.373 for diflunisal and its impurity, respectively. RSD values for repeatability testing were 0.268 and 0.569 and for intermediate precision were 0.224 and 0.259 for diflunisal and its impurity, respectively. The proposed method was effectively applied to analysis of studied drug in its tablet formulation. The results obtained by it were statistically compared with the reported method revealing high accuracy and good precision

A Novel Role for Niemann-Pick Disease Type 2C Protein in Papillae Formation

BACKGROUND: Despite the presence of papillary structures and papillary tumors in humans, the mechanism of papillae formation is unknown. We describe herein a novel role for Niemann-Pick disease type 2C (NPC2) protein, a cholesterol binding protein in the lysosome, in papillae formation. METHODOLOGY/PRINCIPAL FINDING: We examined NPC2 protein expression in surgical samples of papillary tissues by immunohistochemical stain, and all papillary tissues expressed NPC2 protein in the epithelium. To examine our hypothesis of NPC2 protein-mediated papillae formation, we carried out xenograft experiments using wild H460 cells (large cell lung carcinoma cell line) that constitutively expressed abundant NPC2 protein and NPC2 protein-depleted H460 cells by NPC2 shRNA. The xenografts of wild H460 cells and empty shRNA vector cells showed distinct papillae formation, whereas NPC2 protein-depleted H460 cells displayed markedly reduced or no papillae. Since all papillary tissues have open spaces we examined whether NPC2 protein might also contribute to the creation of open spaces. The TUNEL assay in the xenografts of wild and empty shRNA vector H460 cells showed massive cell death, and NPC2 protein-depleted cells displayed minimal cell death. Measurement of caspase 3/7 activities in cultured H460 cells supported NPC2 protein-mediated apoptotic cell death. The presence of excess NPC2 protein, however, did not always produce papillae as seen in the xenografts of CHO cells that were stably transfected with NPC2. CONCLUSIONS/SIGNIFICANCE: The NPC2 protein of certain cells forms papillae coupled with apoptosis that creates open space. This protein may have future applications to modulate papillae formation and papillary growth in tumor tissues

Pleomorphic adenoma of the vulva, clinical reminder of a rare occurrence

Pleomorphic adenoma, also known as mixed tumor, is a benign tumor which typically presents as a painless and persistent mass. The majority of pleomorphic adenomas involve the salivary glands, most commonly the parotid gland. Other sites include breast and skin. It is a rare tumor in the vulva. In this article we are reporting a case of pleomorphic adenoma of labia with characteristic pathologic and clinical findings, as reminder of a common benign neoplasm occurring with rare locality

Significance of lobular intraepithelial neoplasia at margins of breast conservation specimens: a report of 38 cases and literature review

<p>Abstract</p> <p>Background</p> <p>Presence of lobular intraepithelial neoplasia (LIN) is not routinely reported as part of margin assessment in breast conservation therapy (BCT) as in ductal carcinoma in situ (DCIS). With new emerging evidence of LIN as possible precursor lesion, the hypothesis is that LIN at the margin may increase the risk of local recurrence with BCT. The aim is to determine whether there is an increase incidence of recurrence when LIN is found at surgical margins on BCT.</p> <p>Methods</p> <p>We retrospectively reviewed a total of 1,334 BCT at a single institution in a 10 year period. Inclusion criteria are positive margin with LIN from primary BCT containing invasive and/or in situ carcinoma with comparison to the negative control group who had similar diseases with negative margin for LIN.</p> <p>Results</p> <p>We identified 38 cases (2.8%) with LIN either lobular carcinoma in situ/atypical lobular hyperplasia (LCIS/ALH) at a margin on initial BCT with 36% recurrence rate. Of the 38 cases: 5 (13%) were lost to follow-up, 12 (32%) had no further procedures performed and 21 (55%) had re-excision. Out of 21 patients who had re-excisions, 12 (57%) had residual invasive carcinoma or DCIS, three (14%) had pleomorphic LCIS and 4 (19%) showed residual classic type LCIS. 71% had significant residual disease (local recurrence) and 29% had no residual disease. A negative control group consisted of 38 cases. We found two patients with bone or brain metastasis and one local recurrence. Clinical follow up periods range from 1 to 109 months.</p> <p>Conclusions</p> <p>LIN found at a margin on BCT showed a significant recurrent ipsilateral disease. Our study supports the view that LIN seen at the margin may play a role in recurrence.</p