Copy number variations in male breast cancer.

Common copy number variations often contain cancer-related genes and are likely to play a role in carcinogenesis. Different mechanisms of tumorigenesis are suggested in female and male breast cancer because of different molecular profiles. The cytogenetic analysis of GTG-banded chromosomes was performed in six male patients with infiltrating ductal carcinoma and six healthy male controls matched for age. Single-nucleotide polymorphism (SNP) array analysis was performed in male breast cancer (MBC) patients. Cytogenetic analysis found aberrations previously implicated in cancer. SNP array analysis in patients revealed a gain of Xp11.23, 8p23.2, Yq11.221, Yq11.3 (AZF region), 12p11.21, 18q12.1, and 17q21.3; a loss of Yq11.222 and 7q11.21; and a loss of heterozygosity of 4p16.3, 6p12.3, 6p22.2-p21.31, 7p14.2-14.1, 18q11.2-q12.1, 20p11.23-11.1, 20q11.21-11.23, 1q25.2-q25.3, 2q11.1-q11.2, 5q23.1-23.2, 11p15.4-15.3, and 22q13.1-13.31. Some of these variations, especially those of the Y-chromosome, have not been reported earlier. Chromosomal loci identified by SNP array harbor genes were reported to be associated with cancer progression and metastasis, indicating their involvement in MBC also.

RAD51 135G>C polymorphism in esophageal cancer and meta-analysis in gastrointestinal tract cancers.

Background: A functional single-nucleotide polymorphism (SNP), 135G>C in the 5'UTR of the RAD51 gene, affects gene transcription activity with implications for the repair of damaged DNA related to tumorigenesis. Previous limited reported genetic studies to link the 135G>C polymorphism of RAD51 gene to the risk of gastrointestinal tract (GIT) cancers, especially esophageal cancer (EC), have been inconclusive. Materials and Methods: The polymorphism was evaluated by RFLP-PCR in 252 EC patients and 252 healthy controls from Amritsar, Punjab, India, for case-control study. For a meta-analysis, a total of 78 studies on GIT cancers were assessed, out of which 14 eligible studies (including the present study) comprising 2842 cases and 3224 controls were included. Odds ratios (ORs) with 95% confidence intervals (CIs) and Chi-square test were used to assess the association in different inheritance models. Results: The GC genotype (OR: 0.45, 95% CI: 0.29-0.68) and C allele (OR: 0.52, 95% CI: 0.36-0.75) were significantly lower (P = 0.0005) in cases as compared to controls. There was no significant association with any genetic model in the meta-analysis. Conclusion: C allele provides protection for EC in the studied population contrary to previous reports in Polish, Chinese population probably due to ethic differences. Compared with previous meta-analysis on individual GIT cancers, present meta-analysis included all GIT cancers but found no association.

Association of MTHFR 677C>T polymorphism with breast cancer risk: A case-control study and meta-analysis.

Background and Objectives: Breast cancer is a complex, multifactorial disease that arises as a result of interactions between multiple genes and environmental factors. Methylenetetrahydrofolate reductase (MTHFR) is a low susceptibility gene, involved in folate metabolism. It assists in conversion of 5,10-methylenetetrahydrofolate to 5-methyltetrahydrofolate which further leads to DNA methylation. 5,10-methylenetetrahydrofolate assists in conversion of uracil to thymine and purine synthesis for DNA synthesis. MTHFR 677C>T polymorphism alters the activity of MTHFR enzyme potentially effecting DNA repair and synthesis, hence a potential risk for cancer like breast cancer. Hence, the present study was conducted to evaluate association of MTHFR 677C>T polymorphism and breast cancer in Punjabi population. Moreover, a meta-analysis was conducted to address the same. Materials and Methods: A total of 247 breast cancer patients and 247 controls were selected from Punjabi population for analysis using PCR-RFLP method. For meta-analysis, 67 studies were selected, and allele contrast, homozygous, heterozygous, dominant, and recessive models were used to evaluate the association between MTHFR 677C>T and breast cancer. Results: The frequencies of CC, CT, and TT genotype were 68.4% versus 74.5%, 28.7% versus 23.5%, and 2.9% versus 2.0% in patients and controls, respectively. There was no significant difference found. In meta-analysis, significant association was found in overall and Asian population while no significant association was found in Caucasians. Interpretation and Conclusions: MTHFR 677C>T polymorphism is not a risk factor for breast cancer in Punjabi population. Inconsistency with the meta-analysis can be due to ethnic diversity.

Human Epidermal Growth Factor Receptor 2 (HER2) Expression in Colorectal Carcinoma: A Potential Area of Focus for Future Diagnostics.

Objective In this study, we aimed to explore the potential diagnostic utility of human epidermal growth factor receptor 2 (HER2) expression in colorectal carcinoma. We investigated the association of HER2 expression with the type and grade of the tumor along with the pattern, staining intensity, and the percentage of cells stained. Methods This was an observational study involving 50 cases of colorectal carcinoma that underwent immunohistochemistry to analyze the HER2 expression. Results The positive expression of HER2 was seen in 16 (32%) cases. The majority of the study population was between the fifth-seventh decades of life. The most commonly diagnosed tumor was conventional adenocarcinoma with grade II, cytoplasmic pattern, +2 positivity, and moderate intensity. The maximum positivity for HER2 was seen in tumors of the rectum in eight (16%) cases. Conclusion A substantial rate of HER2 overexpression paves the way for it to become a potential future target in cancer therapeutics.

Expression of Cyclin-D1 and p53 as Prognostic Markers in Treatment of Oral Squamous Cell Carcinoma.

Cyclin D1 and p53 play an important role in tumorigenesis of human cancers. The present study aims to evaluate cyclin D1 and p53 expression in resectable OSCC, and to determine their prognostic significance at the end of 5 year follow-up: A total of 100 patients aged 31-74 years, stage 3/4 were recruited. Cyclin D1 and p53 expression in the tumour tissue was estimated by IHC and was statistically correlated with demographic and clinicopathological data and prognosis was evaluated at the end of 5 year outcome. The positive expression rate of cyclin D1 was 50% and p53 it was 40% and they neither showed any statistical significant correlation with each other nor with demographic or clinicopathological data. The OS was 32%.Negative and weak expression predicted better outcomes with regard to DFS and OS. DFS and OS were significantly worse in patients of overexpressed cyclin D1 (p < 0.001) and p53 (p = 0.008). Cyclin D1 is a better prognostic marker as compared to p53 for both DFS and OS. p53 expression (high versus low) for disease free non-survival and overall nonsurvival showed an OR of 3.576 (p = 0.003) and 8.803(p < 0.001) respectively for strong expression while in case of cyclin D1 it showed an OR of 13.067(p < 0.001) and 37.465(p < 0.001) for strong expression.So higher the level of expression of tumour markers higher is the odds ratio so poorer is the prognosis. Overexpression of cyclin D1 and p53 was significantly associated with poor prognosis in terms of DFS and OS.

Association of VEGF haplotypes with breast cancer risk in North-West Indians.

BACKGROUND: Angiogenesis is a complex and coordinated process regulated by different growth factors and is one of the hallmark features of cancer. VEGF is one of the most important endothelial cell mitogen and has a critical role in normal physiological and tumor angiogenesis. The objective of this study was to investigate the potential association of haplotypes of six VEGF polymorphisms with breast cancer risk in North-West Indians. METHODS: Samples of 250 breast cancer patients and 250 age and sex matched controls were genotyped for VEGF -2578C/A, -2549I/D, -460T/C, +405C/G, -7C/T and +936C/T polymorphisms. Haplotypes were generated to determine the better contribution of VEGF polymorphisms to breast cancer risk. RESULTS: Haplotypes CDTCCC (OR = 0.56, 95%CI, 0.38-0.81; p = 0.003) and CDTGCC (OR = 0.63, 95%CI, 0.44-0.92; p = 0.018) of VEGF -2578C/A, -2549I/D, -460T/C, +405C/G, -7C/T and +936C/T polymorphisms were significantly associated with decreased risk of breast cancer. CDTCCC haplotype was also significantly associated with reduced risk of breast cancer in pre and post menopausal as well as both obese and non obese patients. Haplotype CDTGCC was marginally associated (p = 0.07) with reduced risk of breast cancer in non-obese patients as compared with non-obese controls where as haplotype AICGTC was marginally associated (p = 0.09) with reduced risk of breast cancer in obese patients when compared with non-obese patients. The CDTGCC haplotype was significantly associated with increased risk of breast cancer in premenopausal obese patients (OR = 1.98, 95%CI, 1.10-3.56; p = 0.02). CONCLUSIONS: Our data indicated that CDTCCC and CDTGCC haplotypes of VEGF -2578C/A, -2549I/D, -460T/C, +405C/G, -7C/T and +936C/T polymorphisms were significantly associated with breast cancer risk in North-West Indians. Further studies on multiethnic groups with larger sample size are required to confirm our results.

In silico pathway analysis based on chromosomal instability in breast cancer patients.

BACKGROUND: Complex genomic changes that arise in tumors are a consequence of chromosomal instability. In tumor cells genomic aberrations disrupt core signaling pathways involving various genes, thus delineating of signaling pathways can help understand the pathogenesis of cancer. The bioinformatics tools can further help in identifying networks of interactions between the genes to get a greater biological context of all genes affected by chromosomal instability. METHODS: Karyotypic analyses was done in 150 clinically confirmed breast cancer patients and 150 age and gender matched healthy controls after 72 h Peripheral lymphocyte culturing and GTG-banding. Reactome database from Cytoscape software version 3.7.1 was used to perform in-silico analysis (functional interaction and gene enrichment). RESULTS: Frequency of chromosomal aberrations (structural and numerical) was found to be significantly higher in patients as compared to controls. The genes harbored by chromosomal regions showing increased aberration frequency in patients were further analyzed in-silico. Pathway analysis on a set of genes that were not linked together revealed that genes HDAC3, NCOA1, NLRC4, COL1A1, RARA, WWTR1, and BRCA1 were enriched in the RNA Polymerase II Transcription pathway which is involved in recruitment, initiation, elongation and dissociation during transcription. CONCLUSION: The current study employs the information inferred from chromosomal instability analysis in a non-target tissue for determining the genes and the pathways associated with breast cancer. These results can be further extrapolated by performing either mutation analysis in the genes/pathways deduced or expression analysis which can pinpoint the relevant functional impact of chromosomal instability.

Screening of BRCA1 variants c.190T>C, 1307delT, g.5331G>A and c.2612C>T in breast cancer patients from North India.

The polymorphic variants of BRCA1, which lead to amino acid substitutions, have a known pathogenic role in breast cancer. The present study investigated in North Indian breast cancer patients the association of risk with four reported pathogenic variants of BRCA1: c.190T>C (p.Cys64Arg), 1307delT, g.5331G>A (p.G1738R) and c.2612C>T (p.Pro871Leu). Genotyping was done by PCR-RFLP method in 255 clinically confirmed breast cancer patients and 255 age and gender matched healthy individuals. For c.190T>C, 1307delT and g.5331G>A, all the patients and controls had the wild-type genotype indicating no association with breast cancer risk. For c.2612C>T polymorphism, the frequency of the CC, CT, and TT genotypes was 14.5 vs 15.7%, 59.6 vs 53.7% and 25.9 vs 30.6% in breast cancer patients and controls respectively. The frequency of heterozygotes (CT genotype) was higher in cases than controls but the difference was not statistically significant. Genetic model analysis showed no association of the four analyzed BRCA1 variants with breast cancer risk with any model. The studied variants were not associated with the risk of breast cancer in Punjab, North west India, suggesting a need for further screening of other BRCA1 variants. It is the first reported study on these 4 variants from India.

Association of XRCC1, XRCC2 and XRCC3 Gene Polymorphism with Esophageal Cancer Risk.

AIM: The X-ray repair cross-complementing (XRCC) gene polymorphisms influence esophageal carcinogenesis by altering the DNA repair capacity. The present study was designed to screen five single nucleotide polymorphisms (SNPs) of XRCC genes for their susceptibility to esophageal cancer (EC) risk. There is no previous report on these polymorphisms for EC from India, where EC frequency is high. METHODS: The present study included 497 subjects (213 EC patients and 284 healthy controls). The polymorphisms were screened using the PCR-RFLP method and allele and genotype distribution were compared using chi-square test. Association analysis was done by haplotype analysis and linkage disequilibrium (LD) analysis. Gene-gene interactions were identified using multifactor dimensionality reduction (MDR). The risk was calculated using binary logistic regression. RESULTS: For XRCC1 p.Arg399Gln, a decreased risk for EC was associated with the AA genotype [OR (95% CI): 0.53 (0.3-0.95), p=0.03] even after adjusting for various covariates [OR (95% CI): 0.49 (0.26-0.9), p=0.024] and with the recessive model [OR (95% CI): 0.49 (0.27-0.8), p=0.016]. The GA genotype of p.Arg280His was associated with an increased risk for EC [OR (95% CI): 1.7 (1.0-2.82), p= 0.045] after adjustments. The two XRCC1 polymorphisms, p.Arg399Gln and p.Arg194Trp were in slight LD among EC patients (D̍́=0.845, r 2=0.042). XRCC2 and XRCC3 polymorphisms were not associated with EC risk. CONCLUSION: XRCC1 p.Arg399Gln plays a protective role in the development of the EC. The study is the first report from India, providing baseline data about genetic polymorphisms in DNA repair genes XRCC1, XRCC2 and XRCC3 modulating overall EC risk.

Linkage disequilibrium and haplotypes of five TP53 polymorphisms in oesophageal cancer patients.

The aim of present study was to evaluate the linkage disequilibrium (LD) of p.R72P, PIN3 Ins16bp, p.P47S, p.R213R and r.13494g[a polymorphism of TP53 and their haplotypes association with oesophageal cancer risk in patients from Punjab, northwest India. A total of 466 samples, including 233 oesophageal cancer patients and 233 healthy individuals were analysed. Data analysis revealed the gender specific association. In female group, arginine-proline (RP) genotype (P = 0.08) and P allele (P = 0.07) of p.R72P polymorphism was marginally associated with increased risk of oesophageal cancer. A1A2 genotype (P = 0.06) and A2 allele (P = 0.07) of PIN3 Ins16bp polymorphism was marginally associated with decreased risk of oesophageal cancer in male group. A1A2-GA genotype combination (P = 0.04) of PIN3 and r.13494g[a polymorphisms was significantly associated with decreased risk of oesophageal cancer in male group. In female group, PP-GA genotype combination (P = 0.02) of p.R72P and r.13494g[a polymorphisms and RP-A1A1-GG genotype combination (P = 0.04) of p.R72P, PIN3 and r.13494g[a polymorphisms was significantly associated with increased risk of oesophageal cancer. We observed moderate LD between two intronic polymorphisms PIN3 Ins16bp and r.13494g[a (D´ = 0.90; r2 = 0.68). Haplotype analysis revealed that none of the haplotype combination was associated with oesophageal cancer risk when both the genders were considered. Stratification on the basis of gender showed that P-A2-P-A-A haplotype of p.R72P, PIN3 Ins16bp, p.P47S, p.R213R and r.13494g[a polymorphisms was marginally associated with reduced oesophageal cancer risk in male group (P = 0.08). Replication of these findings in independent cohorts may be insightful for the role of TP53 in oesophageal cancer pathogenesis.

Hypoxia-induced factor-1 alpha, vascular endothelial growth factor expression in BRCA1-related breast cancer: A prospective study in tertiary care hospital.

INTRODUCTION: Breast cancer is the commonest cause of death among middle aged women. BRCA1 associated tumors carry a poor prognosis. Angiogenesis is considered necessary for tumor growth and for its metastasis. Hypoxia stimulates HIF-1α which then activates transcription of various proangiogenic cytokines like VEGF. In the present study we examined HIF-1α expression, sVEGF levels and BRCA1 mutations and their relation with clinicopathological parameters. We also determined whether the angiogenic markers have different role in angiogenesis in BRCA1 related cancers as compared to sporadic breast cancers. MATERIALS AND METHODS: The study was conducted on 50 cases of breast cancer specimens. Histopathological typing and grading was done followed by immunohistochemistry for BRCA1 and HIF-1α. VEGF was done in the serum by ELISA. RESULTS: All the tumors were infiltrating ductal carcinoma NOS. 16 cases were reported grade II and 34 cases as grade III. On immunohistochemistry, 27 cases showed BRCA1 positivity and HIF-1α was positive in 39 cases. sVEGF levels were increased in 21 cases (42%). BRCA1 positivity, HIF-1α expression and increased VEGF levels were significantly associated with higher grade and lymph node metastasis. There was significant correlation of BRCA1 positivity with increased HIF-1α expression (P = 0.009) and increased sVEGF levels (P = 0.005). CONCLUSION: Our findings suggest that BRCA 1 positive tumors have unique molecular profile and different mechanism of tumorigenesis. Such tumors are associated with increased HIF-1α expression and VEGF levels.

Immunohistochemical expression of Ets-related gene-transcriptional factor in adenocarcinoma prostate and its correlation with Gleason score.

BACKGROUND: Prostate carcinoma is the second leading cause of cancer-related deaths in males worldwide. The burden is expected to grow 1.7 million new cases and 499,000 new deaths by 2030. In developing countries such as India, prostate carcinoma will show an increase by 140% in the next few years. Although the diagnosis of prostate carcinoma can usually be made on histological features, now a days many immunohistochemical (IHC) markers are used to distinguish it from benign mimickers as well as in predicting prognosis and treatment. Out of these markers, Ets-related gene (ERG product) is a proto-oncogene which participates in chromosomal translocations and is frequently over expressed in prostate carcinoma which harbors ERG-transmembrane protease, serine 2 fusion. MATERIALS AND METHODS: Fifty cases of carcinoma prostate diagnosed in needle biopsies and prostatic chips, in the Department of Pathology of a tertiary care teaching hospital in Punjab, India, were included in the present study. The slides were observed under the light microscope, and Gleason scoring was done using the 2005 International Society of Urological Pathology modified Gleason system. IHC study for ERG expression was done on all the cases, for which anti-ERG monoclonal rabbit clone antibody EP111 (Dako, Denmark) was used. Lymphocytes and endothelial cells were taken as in built positive controls for staining. The intensity of ERG positivity was scored as no staining (0), weak staining (+1), moderate staining (+2) and intense staining (+3). The H score was then calculated by multiplying the intensity of the stain with the percentage (0-100) of the cells showing that staining intensity. The H-score has a range of 0-300. The relationship between IHC expression and clinico-pathological parameters was compared and analyzed using Chi-square test. P < 0.05 was considered statistically significant. RESULTS: Majority of patients included in the study were in the age group of 61-80 (84% of the total). When ERG expression was studied with age-specific rates, it was not found to be statistically significant. The most common pattern noted in the present study was 4 + 3, constituting 36% of total, followed by 3 + 4 constituting 32%. Calculating the score, the majority of patients had a Gleason score of 5-8, constituting 76% of total. Out of the total fifty cases of prostate carcinoma, ERG was positive in 29 cases (58%) and negative in 21 cases (42%). Fourteen out of 21 (48%) of the ERG positive cases had an intensity score of 3. When the ERG intensity was correlated with the Gleason score group, it was seen that patients having Gleason score 7-8 showed ERG positivity in 19 out of 38 cases (50%), with 11/19 (57%) cases showing an ERG intensity score of 3. The Gleason score group 9-10 showed ERG positivity in 83% (10/12) cases, 20% (2/10) cases showing intensity score of 3. This correlation was found to be statistically significant. CONCLUSION: ERG immunostaining was performed in a small Indian cohort of prostate cancer patients, diagnosed in trucut biopsy specimens and prostatic chips. ERG expression was found in 58% patients. An increase in the ERG expression was observed with an increase in Gleason score. The intensity of ERG expression, however, decreased with an increasing Gleason score.

Pituitary Chondrosarcoma presenting as a sellar and suprasellar mass with parasellar extension: An Unusual presentation.

Chondrosarcoma is a mesenchymal tumor composed of tumor cells producing cartilage. It is more common in older age and often affects the axial skeleton. We report a rare case of chondrosarcoma mimicking a sellar and suprasellar mass with parasellar extension. A 40 yr woman presented with decreasing visual acuity and headache. Magnetic resonance (MR) image revealed a cystic sellar and suprasellar mass with parasellar extension showing mild enhancing solid component. It favored the diagnosis of craniopharyngioma. The patient underwent trans-sphenoidal partial resection of the tumor resulting in removal of the sellar mass. However, the suprasellar mass could not be excised completely due to limited surgical field. The pathologic diagnosis was chondrosarcoma. Eight months after the operation, pterional approach was performed to remove the remaining mass. Intraoperative findings confirmed that the mass originated from dorsum sellae.

Association of the -2518 A/G Polymorphism of MCP-1 with Breast Cancer in Punjab, North-West India.

BACKGROUND: Monocyte chemoattractant protein-1 (MCP-1) is a major chemokine thought to be responsible for monocyte and T-lymphocyte recruitment in acute inflammatory conditions and recruitment of macrophages in tumors. It is also implicated in cardiovascular disease, rheumatoid arthritis and chronic obstructive pulmonary disease. The aim of the present study was to investigate the correlation between MCP-1 -2518 A/G polymorphism and breast cancer risk in patients from Amritsar city of Punjab state in North-West India. MATERIALS AND METHODS: We screened DNA samples of 200 sporadic breast cancer patients and 200 age and gender matched unrelated healthy individuals for MCP-1 -2518 A/G polymorphism using the PCR-RFLP method. RESULTS: A significantly increased frequency of the GG genotype was observed in patients as compared to controls. Individuals carrying the MCP1 -2518GG genotype had a two fold risk for breast cancer (OR=2.06, 95%CI, 1.06-3.98; p=0.03). Genetic models analysis revealed a significant association between MCP-1 -2518 A/G polymorphism and cancer risk in homozygous co-dominant (OR=2.06, 95%CI, 1.06-3.98; p=0.03) and recessive (OR=1.97, 95%CI, 1.05-3.70; p=0.03) models. CONCLUSIONS: We conclude that the GG genotype of the MCP-1-2518 A/G polymorphism is associated with increased risk to breast cancer in Punjab, North-West India.

No Association between the CCR5Δ32 Polymorphism and Sporadic Esophageal Cancer in Punjab, North-West India.

BACKGROUND: Chemokines and their receptors influence carcinogenesis and cysteine-cysteine chemokine receptor 5 (CCR5) directs spread of cancer to other tissues. A 32 base pair deletion in the coding region of CCR5 that might alter the expression or function of the protein has been implicated in a variety of immune-mediated diseases. The action of antiviral drugs being proposed as adjuvant therapy in cancer is dependent on CCR5 wild type status. In the present study, distribution of CCR5Δ32 polymorphism was assessed in North Indian esophageal cancer patients to explore the potential of using chemokine receptors antagonists as adjuvant therapy. MATERIALS AND METHODS: DNA samples of 175 sporadic esophageal cancer patients (69 males and 106 females) and 175 unrelated healthy control individuals (69 males and 106 females) were screened for the CCR5Δ32 polymorphism by direct polymerase chain reaction (PCR). RESULTS: The frequencies of wild type homozygous (CCR5/CCR5), heterozygous (CCR5/Δ32) and homozygous mutant (Δ32/Δ32) genotypes were 96.0 vs 97.72%, 4.0 vs 1.71% and 0 vs 0.57% in patients and controls respectively. There was no difference in the genotype and allele frequencies of CCR5Δ32 polymorphism in esophageal cancer patients and control group. CONCLUSIONS: The CCR5Δ32 polymorphism is not associated with esophageal cancer in North Indians. As the majority of patients express the wild type allele, there is potential of using antiviral drug therapy as adjuvant therapy.

Comparative Changes Noted in Renal Biopsies on Light Microscopy of ANCA Positive Vs ANCA Negative Serology.

OBJECTIVES: Pauci-immune glomerulonephritis is the commonest cause of rapidly progressive glomerulonephritis (RPGN) which is associated with increased mortality and morbidity. More than 90% of these patients have serological presence of either antineutrophil cytoplasmic antibodies (ANCA), of cytoplamic (C) or perinuclear (P) type. "Immunofluoresence studies" exhibiting minimal or no fluorescence is diagnostic in all such cases. The present study aims to study the differences between renal biopsies of serologically ANCA negative versus ANCA positive individuals. MATERIALS AND METHODS: One hundred and twenty renal biopsies (of clinically suspected cases of systemic vasculitis) were sub-divided sub-divided under the heading of serologically ANCA positive and serologically ANCA negative; and scoring them by means of a semi-quantitative scoring system devised at the beginning of the study to identify statistically significant, specific light microscopic features in the sub-components of renal biopsy. RESULTS: Fifteen parameters were found to be statistically significantly (p-value <0.05) in ANCA positive serological cases. These were glomerular capillary loop infiltration by neutrophils, cellular crescents, fibro-cellular crescents, glomerular fibrinoid necrosis, glomerular sclerosis, peri-glomerular infiltration, interstitial oedema, interstitial eosinophils, tubular atrophy, tubular necrosis, tubulitis, arterial hyalinization, arterial necrosis, arterial vessel wall polymorpho nuclear infiltrate and myointimal hypertrophy. CONCLUSION: The presence of above parameters in a renal biopsy report of a patient (in absence of facilities of autoimmune serology and immunofluoresence) can alert both nephrologist and nephropathologist to keep a possibility of renal symptoms arising out of systemic vasculitis.

Association of VEGF and VEGFR1 polymorphisms with breast cancer risk in North Indians.

The aim of present study was to evaluate the relationship between vascular endothelial growth factor (VEGF) -2578C/A, -2549I/D, -460T/C and -7C/T and VEGFR1 -710C/T polymorphisms with risk to breast cancer in North Indians. A total of 204 sporadic breast cancer patients and 204 controls were recruited for this case-control study. Significantly increased frequency of II genotype of -2549I/D polymorphism was observed in patients as compared to control individuals (odds ratio (OR) = 2.76, 95 % confidence interval (CI), 1.55-4.92; p = 0.0005). VEGF -2578AA genotype (OR = 2.87; 95 % CI, 1.61-5.10; p = 0.0003) and A allele (OR = 1.65, 95 % CI, 1.25-2.18; p = 0.0004) were found to be associated with increased risk for breast cancer. Individuals carrying CC genotype (OR = 2.23, 95 % CI, 1.25-3.97) and C allele (OR = 1.42, 95 % CI, 1.07-1.87) of VEGF -460T/C polymorphism were at higher risk of breast cancer. There was no significant difference in genotype and allele distribution of VEGF -7C/T and VEGFR1 -710C/T polymorphisms between cases and control individuals (p > 0.05). Linkage disequilibrium analysis showed a strong linkage between VEGF -2549I/D and -2578C/A polymorphisms (Lewontin's [Formula: see text] = 0.99; r (2) = 0.97), -2549I/D and -460T/C ([Formula: see text] = 0.94; r (2) = 0.84), and -2578C/A and -460T/C polymorphisms ([Formula: see text] = 0.93; r (2) = 0.83). In the present study, we concluded that VEGF -2549I/D, -2578C/A and -460T/C polymorphisms are associated with risk to breast cancer in Punjab, North India.

No association of hypoxia inducible factor-1α gene polymorphisms with breast cancer in North-West Indians.

BACKGROUND: Hypoxia inducible factor-1 alpha (HIF-1α) is the key regulator of cellular responses to hypoxia and plays a central role in tumour growth. Presence of Single nucleotide polymorphisms (SNPs) in the critical regulatory domains of HIF-1α may result in the overexpression of the protein and subsequent changes in the expression of the downstream target genes. The aim of study was to investigate the association of three SNPs (g.C111A, g.C1772T and g.G1790A) of HIF-1α with the risk of breast cancer in North Indian sporadic breast cancer patients. MATERIALS AND METHODS: A total of 400 subjects, including 200 healthy controls and 200 patients with breast cancer were recruited in this study. Genotypes were determined using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. RESULTS: The CC and CA genotype frequency of HIF-1α g.C111A polymorphism was 100 vs 99% and 0 vs 1% in breast cancer patients and healthy controls respectively. The frequencies of CC, CT and TT genotype of g.C1772T polymorphism were 76 vs 74.5%, 19 vs 21% and 5 vs 4.5% in breast cancer patients and control individuals respectively. There was no significant difference in genotype and allele frequencies of HIF-1α g.C1772T polymorphism between cases and control individuals (p>0.05). For g.G1790A genotypes, all patients and controls had only GG genotype. CONCLUSIONS: The three HIF-1α polymorphisms (g.C111A, g.C1772T and g.G1790A) are not associated with breast cancer risk in North-West Indian patients.

Analysis of TP53 polymorphisms in North Indian sporadic esophageal cancer patients.

BACKGROUND: To investigate the relationship of five TP53 polymorphisms (p.P47S, p.R72P, PIN3 ins16bp, p.R213R and r.13494g>a) with the esophageal cancer (EC) risk in North Indians. MATERIALS AND METHODS: Genotyping of p.P47S, p.R72P, PIN3 ins16bp, p.R213R and r.13494g>a polymorphisms of TP53 in 136 sporadic EC patients and 136 controls using polymerase chain reaction and PCR-RFLP. RESULTS: The frequencies of genotype RR, RP and PP of p.R72P polymorphism were 16.91 vs 26.47%, 58.82 vs 49.27% and 24.27 vs 24.27% among patients and controls respectively. We observed significantly increased frequency of RP genotype in cases as compared to controls (OR=1.87, 95% CI, 1.01-3.46, p=0.05). The frequencies of genotype A1A1, A1A2 and A2A2 of PIN3 ins16bp polymorphism were 69.12 vs 70.59%, 27.20 vs 25% and 3.68 vs 4.41% among patients and controls. There was no significant difference among genotype and allele distribution between patients and controls. The frequencies of genotype GG, GA and AA of r.13494g>a polymorphism were 62.50 vs 64.70%, 34.56 vs 30.15% and 2.94 vs 5.15% among patients and controls respectively. No significant difference between genotype and allele frequency was observed in the patients and controls. For p.P47S and p.R213R polymorphisms, all the cases and controls had homozygous wild type genotype. The RP-A1A1-GG genotype combination shows significant risk for EC (OR=2.01, 95%CI: 1.01-3.99, p=0.05). CONCLUSIONS: Among the five TP53 polymorphisms investigated, only p.R72P polymorphism may contributes to EC susceptibility.

Cytological diagnosis of follicular carcinoma thyroid metastasis in pelvic muscles-a rare and unusual site.

Distant metastasis of thyroid neoplasm as an initial presentation is rarely encountered. The present case report describes a chance diagnosis of follicular carcinoma thyroid (FCT) metastasis in a 75-year-old female who was presented with symptoms related to pelvic mass. This is a rare site of reporting as only three cases have been reported previously at the first diagnosis. It is important to identify the presence of distant metastasis as it is the most important prognostic indicator (associated with 50% mortality). This is significant as this has a direct bearing upon its treatment and managing the patient. Hence more awareness is required by both diagnosticians and clinicians regarding this.