Primary central nervous system lymphomas: Indian experience, and review of literature

Primary central nervous system lymphomas (PCNSLs) are a rare form of non-Hodgkin\u2032s lymphoma which arise within and remain confined primarily to the central nervous system (CNS). They generally account for 1-2% of all primary brain tumors and are reported to be on the rise due to the Acquired Immune Deficiency Syndrome (AIDS) epidemic. Aims and Objectives: To study the clinicopathological and immunophenotypic characteristics of PCNSLs and look for any differences in PCNSLs reported in India from those in other countries. Materials and Methods : All cases of PCNSLs between January 1998 and December 2006 were reviewed. Presence of lymphadenopathy, organomegaly and bone marrow study was done to exclude the possibility of secondary involvement by lymphoma. The diagnosis was confirmed by histopathology with Hematoxylin and Eosin and reticulin stains. Immunohistochemistry (IHC) with leucocyte common antigen (LCA), CD 20 and CD 3 was performed on available blocks. The immune status was evaluated by clinical examination and human immunodeficiency virus (HIV) serology (since 1996). Results : In a 19-year study period, there were 56 patients of PCNSLs, accounting for 1.07% of all intracranial neoplasms. The patients ranged from 10-75 years of age with a median age of 42 years. Barring one patient who was HIV positive, all the others were immunocompetent. All cases were diffuse large cell lymphomas on histopathology. IHC with LCA and CD 20 revealed positivity in 100% and 86.4% cases respectively. There was a single case of CD 3 positive T-cell lymphoma. In the present study, PCNSLs occurred in young immunocompetent patients and majority were diffuse large B cell lymphomas

Primary central nervous system lymphomas: Indian experience, and review of literature

Primary central nervous system lymphomas (PCNSLs) are a rare form of non-Hodgkin\u2032s lymphoma which arise within and remain confined primarily to the central nervous system (CNS). They generally account for 1-2% of all primary brain tumors and are reported to be on the rise due to the Acquired Immune Deficiency Syndrome (AIDS) epidemic. Aims and Objectives: To study the clinicopathological and immunophenotypic characteristics of PCNSLs and look for any differences in PCNSLs reported in India from those in other countries. Materials and Methods : All cases of PCNSLs between January 1998 and December 2006 were reviewed. Presence of lymphadenopathy, organomegaly and bone marrow study was done to exclude the possibility of secondary involvement by lymphoma. The diagnosis was confirmed by histopathology with Hematoxylin and Eosin and reticulin stains. Immunohistochemistry (IHC) with leucocyte common antigen (LCA), CD 20 and CD 3 was performed on available blocks. The immune status was evaluated by clinical examination and human immunodeficiency virus (HIV) serology (since 1996). Results : In a 19-year study period, there were 56 patients of PCNSLs, accounting for 1.07% of all intracranial neoplasms. The patients ranged from 10-75 years of age with a median age of 42 years. Barring one patient who was HIV positive, all the others were immunocompetent. All cases were diffuse large cell lymphomas on histopathology. IHC with LCA and CD 20 revealed positivity in 100% and 86.4% cases respectively. There was a single case of CD 3 positive T-cell lymphoma. In the present study, PCNSLs occurred in young immunocompetent patients and majority were diffuse large B cell lymphomas

Experimental conditions affect the outcome of Plasmodium falciparum platelet-mediated clumping assays

<p>Abstract</p> <p>Background</p> <p>Platelet-mediated clumping of <it>Plasmodium falciparum</it>-infected erythrocytes (IE) is a parasite adhesion phenotype that has been associated with severe malaria in some, but not all, field isolate studies. A variety of experimental conditions have been used to study clumping <it>in vitro</it>, with substantial differences in parasitaemia (Pt), haematocrit (Ht), and time of reaction between studies. It is unknown whether these experimental variables affect the outcome of parasite clumping assays.</p> <p>Methods</p> <p>The effects of Pt (1, 4 and 12%), Ht (2, 5 and 10%) and time (15 min, 30 min, 1 h, 2 h) on the clumping of <it>P. falciparum </it>clone HB3 were examined. The effects of platelet freshness and parasite maturity were also studied.</p> <p>Results</p> <p>At low Ht (2%), the Pt of the culture has a large effect on clumping, with significantly higher clumping occurring at 12% Pt (mean 47% of IE in clumps) compared to 4% Pt (mean 26% IE in clumps) or 1% Pt (mean 7% IE in clumps) (ANOVA, p = 0.0004). Similarly, at low Pt (1%), the Ht of the culture has a large effect on clumping, with significantly higher clumping occurring at 10% Ht (mean 62% IE in clumps) compared to 5% Ht (mean 25% IE in clumps) or 2% Ht (mean 10% IE in clumps) (ANOVA, p = 0.0004). Combinations of high Ht and high Pt were impractical because of the difficulty assessing clumping in densely packed IE and the rapid formation of enormous clumps that could not be counted accurately. There was no significant difference in clumping when fresh platelets were used compared to platelets stored at 4°C for 10 days. Clumping was a property of mature pigmented-trophozoites and schizonts but not ring stage parasites.</p> <p>Conclusion</p> <p>The Pt and Ht at which <it>in vitro </it>clumping assays are set up have a profound effect on the outcome. All previous field isolate studies on clumping and malaria severity suffer from potential problems in experimental design and methodology. Future studies of clumping should use standardized conditions and control for Pt, and should take into account the limitations and variability inherent in the assay.</p

Biological predictors of suicidality in schizophrenia

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/65166/1/j.1600-0447.1996.tb09883.x.pd

EpCAM expression varies significantly and is differentially associated with prognosis in the luminal B HER2+, basal-like, and HER2 intrinsic subtypes of breast cancer

BACKGROUND: Epithelial cell adhesion molecule (EpCAM) is frequently expressed in breast cancer, and its expression has been associated with poor prognosis. Breast cancer can be subdivided into intrinsic subtypes, differing in prognosis and response to therapy. METHODS: To investigate the association between EpCAM expression and prognosis in the intrinsic subtypes of breast cancer, we performed immunohistochemical studies on a tissue microarray encompassing a total of 1365 breast cancers with detailed clinicopathological annotation and outcomes data. RESULTS: We observed EpCAM expression in 660 out of 1365 (48%) cases. EpCAM expression varied significantly in the different intrinsic subtypes. In univariate analyses of all cases, EpCAM expression was associated with a significantly worse overall survival. In the intrinsic subtypes, EpCAM expression was associated with an unfavourable prognosis in the basal-like and luminal B HER2(+) subtypes but associated with a favourable prognosis in the HER2 subtype. Consistently, specific ablation of EpCAM resulted in increased cell viability in the breast cancer cell line SKBR3 (ER(−), PR(−), and HER2(+)) but decreased viability in the breast cancer cell line MDA-MB-231 (ER(−), PR(−), and HER2(−) ). CONCLUSION: The differential association of EpCAM expression with prognosis in intrinsic subtypes has important implications for the development of EpCAM-targeted therapies in breast cancer

Time at surgery during menstrual cycle and menopause affects pS2 but not cathepsin D levels in breast cancer

Many studies have addressed the clinical value of pS2 as a marker of hormone responsiveness and of cathepsin D (Cath D) as a prognostic factor in breast cancer. Because pS2 and Cath D are both oestrogen induced in human breast cancer cell lines, we studied the influence of the menstrual cycle phase and menopausal status at the time of surgery on the levels of these proteins in breast cancer. A population of 1750 patients with breast cancer, including 339 women in menstrual cycle, was analysed. Tumoral Cath D and pS2 were measured by radioimmunoassay. Serum oestradiol (E2), progesterone (Pg), follicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels at the day of surgery were used to define the hormonal phase in premenopausal women. There was a trend towards a higher mean pS2 level in the follicular phase compared with the luteal phase (17 ng mg−1and 11 ng mg−1respectively, P= 0.09). Mean pS2 was lower in menopausal patients than in women with cycle (8 ng mg−1and 14 ng mg−1respectively, P= 0.0001). No differences in mean Cath D level were observed between the different phases of the menstrual cycle, or between pre- and post-menopausal women. In the overall population, pS2 was slightly positively associated with E2 and Pg levels and negatively associated with FSH and LH, probably reflecting the link between pS2 and menopausal status. In premenopausal women, no association was found between pS2 and E2, Pg, FSH or LH levels. There were no correlations between Cath D level and circulating hormone levels in the overall population. However, in the subgroup of premenopausal women with ER-positive (ER+) tumours, E2 was slightly associated with both pS2 and Cath D, consistent with oestrogen induction of these proteins in ER+ breast cancer cell lines. There are changes in pS2 level in breast cancer throughout the menstrual cycle and menopause. This suggests that the choice of the pS2 cut-off level should take the hormonal status at the time of surgery into account. In contrast, the level of Cath D is unrelated to the menstrual cycle and menopausal status. 1999 Cancer Research Campaig

Loss of Ep-CAM (CO17-1A) expression predicts survival in patients with gastric cancer

Preoperative staging of gastric cancer is difficult and not optimal. The TNM stage is an important prognostic factor, but it can only be assessed reliably after surgery. Therefore, there is need for additional, reliable prognostic factors that can be determined preoperatively in order to select patients who might benefit from (neo) adjuvant treatment. Expression of immunohistochemical markers was demonstrated to be associated with tumour progression and metastasis. The expression of p53, CD44 (splice variants v5, v6 and v9), E-cadherin, Ep-CAM (CO17-1A antigen) and c-erB2/neu were investigated in tumour tissues of 300 patients from the Dutch Gastric Cancer Trial, investigating the value of extended lymphadenectomy compared to that of limited lymphadenectomy). The expression of tumour markers was analysed with respect to patient survival. Patients without loss of Ep-CAM-expression of tumour cells (19%) had a significantly better 10-year survival (P<0.0001) compared to patients with any loss: 42% (s.e.=7%) vs 22% (s.e.=3%). Patients with CD44v6 (VFF18) expression in more than 25% of the tumour cells (69% of the patients) also had a significantly better survival (P=0.01) compared to patients with expression in less than 25% of the tumour cells: 10 year survival rate of 29% (s.e.=3%) vs 19% (s.e.=4%). The prognostic value of both markers was stronger in stages I and II, and independent of the TNM stage. Ep-CAM and CD44v6-expression provides prognostic information additional to the TNM stage. Loss of Ep-CAM-expression identifies aggressive tumours especially in patients with stage I and II disease. This information may be helpful in selecting patients suitable for surgery or for additional treatment pre- or postoperatively

Association between full service and fast food restaurant density, dietary intake and overweight/obesity among adults in Delhi, India

Abstract Background The food environment has been implicated as an underlying contributor to the global obesity epidemic. However, few studies have evaluated the relationship between the food environment, dietary intake, and overweight/obesity in low- and middle-income countries (LMICs). The aim of this study was to assess the association of full service and fast food restaurant density with dietary intake and overweight/obesity in Delhi, India. Methods Data are from a cross-sectional, population-based study conducted in Delhi. Using multilevel cluster random sampling, 5364 participants were selected from 134 census enumeration blocks (CEBs). Geographic information system data were available for 131 CEBs (n = 5264) from a field survey conducted using hand-held global positioning system devices. The number of full service and fast food restaurants within a 1-km buffer of CEBs was recorded by trained staff using ArcGIS software, and participants were assigned to tertiles of full service and fast food restaurant density based on their resident CEB. Height and weight were measured using standardized procedures and overweight/obesity was defined as a BMI ≥25 kg/m2. Results The most common full service and fast food restaurants were Indian savory restaurants (57.2%) and Indian sweet shops (25.8%). Only 14.1% of full service and fast food restaurants were Western style. After adjustment for age, household income, education, and tobacco and alcohol use, participants in the highest tertile of full service and fast food restaurant density were less likely to consume fruit and more likely to consume refined grains compared to participants in the lowest tertile (both p < 0.05). In unadjusted logistic regression models, participants in the highest versus lowest tertile of full service and fast food restaurant density were significantly more likely to be overweight/obese: odds ratio (95% confidence interval), 1.44 (1.24, 1.67). After adjustment for age, household income, and education, the effect was attenuated: 1.08 (0.92, 1.26). Results were consistent with further adjustment for tobacco and alcohol use, moderate physical activity, and owning a bicycle or motorized vehicle. Conclusions Most full service and fast food restaurants were Indian, suggesting that the nutrition transition in this megacity may be better characterized by the large number of unhealthy Indian food outlets rather than the Western food outlets. Full service and fast food restaurant density in the residence area of adults in Delhi, India, was associated with poor dietary intake. It was also positively associated with overweight/obesity, but this was largely explained by socioeconomic status. Further research is needed exploring these associations prospectively and in other LMICs

Clinicopathologic study associated with long-term survival in Japanese patients with node-negative breast cancer

This study was undertaken to determine the absolute and relative value of blood vessel invasion (BVI) using both factor VIII-related antigen and elastica van Gieson staining, proliferating cell nuclear antigen (PCNA), p53, c- erb B-2, and conventional prognostic factors in predicting relapse-free survival (RFS) and overall survival (OS) rates associated with long-term survival in Japanese patients with node-negative breast cancer. Two hundred patients with histological node-negative breast cancer were studied. We investigated nine clinicopathological factors, including PCNA, p53, c- erb B-2 using permanent-section immunohistochemistry, clinical tumour size (T), histological grade (HG), mitotic index (MI), tumour necrosis (TN), lymphatic vessel invasion (LVI) and BVI, followed for a median of 10 years (range 1–20). Twenty-one patients (10.5%) had recurrence and 15 patients (7.5%) died of breast cancer. Univariate analysis showed that BVI, PCNA, T, HG, MI, p53, c- erb B-2 and LVI were significantly predictive of 20-year RFS or OS. Multivariate analysis showed that BVI (P = 0.0159, P = 0.0368), proliferating cell nuclear antigen (PCNA) (P = 0.0165, P = 0.0001), and T (P = 0.0190, P = 0.0399) were significantly independent prognostic factors for RFS or OS respectively. BVI, PCNA and T were independent prognostic indicators for RFS or OS in Japanese patients with node-negative breast cancer and are useful in selecting high-risk patients who may be eligible to receive strong adjuvant therapies. © 2000 Cancer Research Campaig

Low levels of cathepsin D are associated with a poor prognosis in endometrial cancer

Total cytosolic cathepsin D (Cat D) levels were estimated by an immunoradiometric assay in a series of 156 consecutive patients with surgical stages I–III primary endometrial adenocarcinoma. Simultaneously, the tissue content of both oestrogen (ER) and progesterone (PR) receptors, and p185HER-2/neu, DNA content (ploidy), and the fraction of S-phase cells (S-phase) were also estimated. Tumoral Cat D content ranged from 0 to 243 pmol mg−1 protein (median 44 pmol mg−1 protein) and was not associated with any of the established clinicopathological and biological prognostic variables, with the exception of a weak positive correlation with the tumoral p185HER-2/neu levels. Univariable analysis performed on a subset of 97 patients, followed for a minimum of 2 years or until death, showed that patient age at diagnosis, high histological grade, advanced surgical stage, vascular invasion, positive peritoneal cytology, low levels of Cat D, negative ER and PR status, aneuploidy, and high S-phase were predictive of the presence of persistent or recurrent disease. However, multivariable analysis revealed that only histological grade, surgical stage, Cat D and PR were significantly associated with the patient's outcome. From these findings, we conclude that Cat D is an independent prognostic factor in endometrial adenocarcinoma, its low levels being associated with a worse clinical outcome. © 1999 Cancer Research Campaig