Genetic profiles of different ethnicities living in Karachi as regards to tobacco-metabolising enzyme systems and the risk of oral cancer.

OBJECTIVE: To detect polymorphisms of CYP1A1, GSTM1 and GSTT1 gene loci among various tobacco-consuming ethnicities in an urban centre, and to relate these with susceptibility to oral cancer. METHODS: The cross-sectional, case-control study was conducted at Ziauddin University, Karachi, and the Dow University of Health Sciences, Karachi, from 2011 to 2016, and comprised patients having oral squamous cell carcinoma in group A, with oral precancerous lesions in group B, and tobacco habit-matched controls in group C. Routine histopathology was followed by molecular analysis through polymerase chain reaction and polymerase chain reaction-restriction fragment length polymorphism techniques. Data was analysed using SPSS 20. RESULTS: Of the 358 subjects, 150(42%) were in group A, 100(28%) in group B, and 108(30%) in group C. There were 190(53.1%) Urdu-speaking subjects, 42(11.7%) Memoni-speaking, 37(10.3%) Sindhi-speaking, 34(9.5%) Balochi-speaking, 25(7%) Pashto-speaking, 15(4.2%) Punjabi-speaking, and 15(4.2) of other ethnicities. Among the Urdu-speaking ethnicity, CYP1A1 MspI heterozygous variant was the most prevalent genotype ingroup A 50(66.7%), group B 37(62.7%) and group C 36(64.3%). The homozygous variant was equally distributed in group A 8(13.5%) and group B 10(13.3%), while it remained quite low in group C 4(7.1%). Homozygous genotype was most common in Pashto-speaking subjects in group A 4(57.1%). In Urdu-speaking subjects, GSTM1-null genotype was mostly found in group B 19(32.2%), while GSTT1-null genotype was most common in group A 12(16%). Other than Urdu-speaking, GSTM1-null variant was most frequent in Sindhi-speaking subjects in group B 8(80%). CONCLUSIONS: Intra-ethnic distribution of tobacco-metabolising enzyme genes can be considered an important contributor to oral cancer risk in the population of Karachi.

Gene-gene and gene-environment interaction: An important predictor of oral cancer among smokeless tobacco users in Karachi.

OBJECTIVE: To determine the risk for oral cancer caused by simultaneous occurrence of more than one of the tested cytochrome P450 CYP1A1 MspI, glutathione S-transferase M1 null gnd Glutathione S-transferases T1 null gene polymorphisms. METHODS: The cross-sectional case-control study was conducted from December 2011 to October 2016 at the Ziauddin University, Karachi, in collaboration with Dow University of Health Sciences, Karachi, and comprised oral squamous cell carcinoma cases in group A and healthy tobacco habit-matched controls in group B. All investigations were done using standardised laboratory protocols. The outcomes were determined in terms of association of various combinations of cytochrome P450 1A1MspI, glutathione S-transferasesM1 null and glutathione S-transferases T1 null polymorphisms with oral cancer. Data was analysed using SPSS 20. RESULTS: Of the 238 subjects, 140(58.8%) were in group A and 98(41.2%) were in group B. Mean ages in group A and B were 47.1±12.22 and 41.6±14.58 years, respectively. Male/Female ratio in group A was 1.88:1 while 83.4% were using tobacco. When cytochrome P450 1A1MspI homozygous (m2/m2) and glutathione S-transferases M1 null variants occured simultaneously in an individual, an odds ratio of 12.8 (95% confidence interval: 1.20-135.5; p=0.03) among overall tobacco chewers was observed. For glutathione S-transferases M1 not null and glutathione S-transferases T1 null variant combination among overall tobacco users, the conferred odds ratio was 4.58 (95% confidence interval: 0.99-21.2; p=0.05). The other studied gene combinations did not reveal significant associations (p>0.05). CONCLUSIONS: A higher risk of oral squamous cell carcinoma was found to be associated with combined-gene polymorphisms of phase I and phase II enzymes than that attributed to a single-gene polymorphism.

Circulating miR-21 as a prognostic and predictive biomarker in oral squamous cell carcinoma.

BACKGROUND & OBJECTIVE: The high-throughput analysis of circulating microRNAs (miRNAs) is an active area of biomarker research. The oral cancer remains a common cancer among Pakistani males that continues to present at an advance stage, thus exhibiting poor survival. MiRNA 21 (miR-21) is the most consistently over-expressed miRNA in different types of tumor tissues. However, information regarding expression of miR-21 in plasma remains to be resolved. Therefore, present study was designed to investigate if miR-21 was expressed in plasma of patients with oral cancer, and further explore its diagnostic and prognostic potential. METHODS: Present study was conducted at Ziauddin University and Karachi Institute of Radiotherapy and Nuclear Medicine (KIRAN). Histologically confirmed cases of oral squamous cell carcinoma were recruited from Oncology Department of Ziauddin Hospital between 2013 and 2017. Controls were carefully selected after considering age, gender and socioeconomic condition. MiRNA was extracted and immediately reverse transcribed to cDNA. MiR-21 expression was evaluated using probes specifically designed for Real time quantitative polymerase chain reaction. RESULTS: A significant over expression of miRNA 21 was observed in histologically confirmed cases as compared to controls. The increased expression of miRNA 21 was also reported to be associated with tumor size, metastasis and local invasion (p<0.05). CONCLUSION: The expression of circulating miR-21 in plasma samples of oral cancer patients makes it a promising diagnostic and prognostic marker.

Liver histology in asymptomatic Hepatitis-C virus positive blood donors.

OBJECTIVE: To assess the Histological alteration of liver in asymptomatic HCV PCR positive family blood donors. METHODS: This is a prospective cross sectional study carried out at Blood Transfusion Services, Clinical & Molecular Laboratory and Pakistan Health Research Council, Jinnah Postgraduate Medical Centre, Karachi from January 2011 to December 2016. One hundred thirteen (113) Anti HCV and HCV RNA positive family blood donors with normal or slightly raised ALT during three consecutive bimonthly visits were included. After taking consent liver biopsy was done to see the histopathological changes in these study participants. The software program SPSS for windows (Ver.19) was utilized for all statistical analysis. RESULTS: One hundred thirteen blood donors who were Anti HCV and HCV RNA positive were included. Ninety eight were male and 15 Female with a mean age of 32.3±6.94 years. Nineteen (16.8%) had significant inflammation of grade 2-3. Nine (8.0%) had significant fibrosis and steatosis was seen in 65 (57.5%) cases. Cirrhosis or advanced liver disease was not found in this series. CONCLUSION: HCV infected individual with normal ALT level having good physical health, without any sign of advanced liver disease on ultrasonography and routine laboratory investigation like AST, Gamma GT, Alkaline Phosphatase, serum albumin, A/G ratio, platelet count and PT, INR might be highly helpful to predict mild or progressive liver disease. Ultimately it reduces the need of liver biopsy, an invasive procedure having significant complications.

Impact of age at diagnosis on clinicopathological outcomes of oral squamous cell carcinoma patients.

OBJECTIVE: A recent trend in diagnosis of oral cancer in young age is observed, however its impact on various clinicopathological parameters needs to be explored. The aim of the current study was to compare and analyze impact of age at diagnosis with clinicopathological parameters of oral squamous cell carcinoma patients. METHODS: In this cross sectional study conducted at Department of Oncology Ziauddin Hospital Karachi, we included histologically confirmed cases of oral squamous cell carcinoma. The patients were categorized as young age group (40yrs and younger) and old age group (41 yrs and above). A total of 115 patients diagnosed between 2013 and 2016 were enrolled in the study. The variables considered were age at diagnosis, sex, site of lesion, positive family history, tumor grade, stage, uric acid level and survival. RESULTS: A statistically significant difference was observed between two age groups in overall survival, uric acid level and positive family history of cancer. No significant difference was observed in tumor location, grade and stage. CONCLUSION: Majority of oral cancer patients present at an advanced stage irrespective of age at diagnosis but young age has an overall improved survival. Moreover, a positive family history of cancer in young age group mandates further exploration of possible role of genetic polymorphisms which might be responsible for early onset of the disease.

Clinicopathological features associated to MiRNA-195 expression in patients with breast cancer: Evidence of a potential biomarker.

BACKGROUND & OBJECTIVE: MiRNAs are a systematic class of small non-coding RNAs with impending role as tumor biomarkers. Our objective was to identify the level of expression of Mir-195 in patients with breast cancer along with its correlation with clinicopathologic features. METHODS: A total of 209 females in which 139 histologically diagnosed breast cancer (BC) cases and 70 healthy controls matched for age, their relative clinical and histopathological findings were recorded from their laboratory reports and hospital record of the patients. Plasma was used for extraction of total RNA and cDNA was prepared by using both miR-195 stem loop RT primers and gene specific antisense primers while U6 IT was used as control. Quantitative real-time PCR (qRT-PCR) for miR-195 expression status was performed and amplification (down regulation) was recorded. RESULTS: Of 139 samples the expression of miR-195 was down regulated in 72.6% cases and the remaining 27.3% cases behaved same as 70 healthy or normal controls. Significant correlation of low miR-195 expression with higher differentiation grade, lymph node metastasis and clinical stage was found. CONCLUSION: Significant correlation between miR-195 expression and some clinicopathological features were recognized. MiR-195 could be used as potential non-invasive, molecular biomarker for early detection of breast cancer.

Comparison of clinicopathological characteristics of lymph node positive and lymph node negative breast cancer.

OBJECTIVE: To record various clinicopathological characteristics of breast cancer (BC) in our population and to find an association between these characteristics and axillary nodal metastasis. METHODS: This cross-sectional study included 150 BC patients from two tertiary care centers in Karachi from 15(th) February, 2013 to 31(st) March, 2015. Frequencies, percentages, and odds ratio were estimated to find out an association between various clinicopathological characteristics and lymph node status using SPSS version 20. RESULTS: Approximately 75.4% patients had axillary lymph node metastasis ('1-3' LN = 34.4% and '>3' LN = 44%). Menopausal status (p <0.013), tumor grades ('II' p <0.03; 'III' p <0.01), and stages ('III' p <0.002; 'IV' p <0.0001), tumor sizes ('T2' p <0.014; 'T3' p <0.002), perineural invasion (PNI) (p <0.007), lymphovascular invasion (LVI) (p <0.0001), and skin and nipple invasion (p <0.024) were significant predictors for '>3' LN metastasis. Association of these variables with '1-3' LN involvement was insignificant. CONCLUSION: Clinical spectrum of BC remains unchanged in 2016 with most of the patients presenting with high-grade, late-stage advanced disease. Moreover, clinicopathological variables, especially primary tumor size, tumor stage and lymphovascular invasion were significant predictors of >3 lymph node metastasis with high accuracy.

Conventional clinical and prognostic variables in 150 oral squamous cell carcinoma cases from the indigenous population of Karachi.

OBJECTIVE: To analyze clinical and prognostic variables of Oral Squamous Cell Carcinoma (OSCC) cases from the indigenous population of Karachi and to correlate with the common risk factor of tobacco habit. METHODS: The study was conducted at Ziauddin University, Karachi. One hundred fifty OSCC cases were collected from the Oncology Department of Ziauddin University Hospital, North Nazimabad, Karachi and Otolaryngology ward of Civil Hospital, Karachi, during 2011 and 2015. The reporting included demographic details and variables like intra-oral subsites, clinical stage and histological grade. Recurrence of tumor after initial resection was also documented. RESULTS: The patient's population comprised of 98 males and 52 females. The mean age was 47.1± 12.22 (range:20-78 years). Maximum numbers were seen in the 41-50 years age group. Urdu-speaking community was the most affected ethnic group (n=75). Clinico-pathological analysis revealed that majority of cases were moderately differentiated (59%) and were either clinical stage II (35%) or IV (29%) tumors. The most common intra-oral subsite came out to be buccal mucosa of cheeks (56%) followed by lateral borders of tongue (21%), lips (13%), alveolar (6%), palate (2.6%) floor of mouth (1.3%), etc. Recurrence was observed in 08 out of 150 cases. All patients underwent primary resection±neck dissection and reconstruction where possible. CONCLUSIONS: Overall experience with oral squamous cell carcinoma shows that it has a high tendency for local invasion as well as dissemination to regional lymph nodes, i.e. cervical lymph nodes, both are associated with a poor prognosis. Preventable risk factor of tobacco chewing has been observed in majority of these cases.

"OMIC" tumor markers for breast cancer: A review.

Breast cancer is a global health issue, and as the tumor burden increases, we need to come up with newer, better technologies which are convenient, cheap, rapid, sensitive with a high specificity. Technological advancements in the field of cancer biomarker has led to the development of techniques such as mass spectrometric analysis and microarray analysis in which genes, proteins and hundreds and thousands of metabolites can be identified with the emergence of genomics, proteomics and metabolomics. This research is focused on finding biomarkers for diagnosis, prognosis, staging, treatment response and targets for chemotherapy, generating a panel of markers which provide better clinical information compared to a single marker in the panel. This review briefly summarizes application of genomics and proteomics followed by key concepts and applications of metabolomics in breast cancer, with the conclusion that an integration of the three "OMIC" technologies may hold the key to future biomarker discovery. SOURCES OF DATA STUDY SELECTION: The information for this review was collected by searching the Google Scholar and PubMed database for English articles published in the period from 2002 to 2015. The search terms included "biomarkers in breast cancer" along with the following search terms: "genomics", "proteomics", "metabolomics", "breast cancer", "mass spectrometry", "molecular markers" and "cancer biomarker". We have endeavored to quote only the primary sources. Titles and abstracts of retrieved studies were assessed first followed by selection and retrieval of selected full text articles.

Increasing Frequency of New Delhi Metallo-beta-Lactamase and Klebsiella pneumoniae Carbapenemase Resistant Genes in a Set of Population of Karachi.

OBJECTIVE: To determine the frequency of Klebsiella pneumoniae Carbapenemase (blaKPC) and New Delhi Metallo-Beta-Lactamase (blaNDM) resistant genes among clinical isolates of Enterobacterales in a set of Karachi population. STUDY DESIGN: An observational study. PLACE AND DURATION OF STUDY: Department of Microbiology, Dr. Ziauddin University Hospital, Karachi, Pakistan, from January 2019 to December 2020. METHODOLOGY: A total of 2100 clinical isolates of Enterobacterales were collected. All isolates of Carbapenem-Resistant Enterobacterales (CRE) (Escherichia coli, Enterobacter and Klebsiella species) on the basis of Meropenem screening test positivity were included in the study. DNA was extracted and PCR was performed for resistant genes detection. Frequencies and percentages were computed for categorical variables and mean values and standard deviation for quantitative variables. RESULTS: Among 2100 isolates of Enterobacterales, the majority were E. coli 1260 (60%), followed by Klebsiella species 462 (22%), and Enterobacter species 210 (10%). The sources of CRE isolates included 34 (25%) from respiratory (tracheal aspirate, pleural fluid, and gastric lavage); 33 (24.26%) urine, 32 (25.53%) pus, 15 (11.03%) blood, and 20 (14.7%) others (ascitic fluid, stents, and tissue). All isolates of CRE were sensitive (100%) to Colistin, Tigecycline and Fosfomycin. Biochemically confirmed CRE 136 (6.5%) isolates, (79 (58%) males and 57 (42%) females), were selected for detecting resistant genes. The PCR showed 32 (23.52%) positive for both NDM and KPC resistant genes, 28 (20.58%) for NDM and 19 (13.97%) for KPC alone. Out of 79 followed up patients, 58 (73.4%) expired while 21 (26.6%) were discharged. CONCLUSION: The frequency of blaNDM and blaKPC resistant genes in CRE isolates depicted increasing trend. Colistin, Fosfomycin, and Tigecycline showed high antimicrobial sensitivities in vitro. Further measures need to be applied for CRE with comprehensive resistant genes detection to curtail antimicrobial resistance. KEY WORDS:  Frequency, KPC, NDM, Klebsiella species, Carbapenemases, Enterobacterales E.coli.

Pattern of histological findings in chronic hepatitis C with alanine transaminase levels below twice the normal value.

OBJECTIVES: To assess the pattern of liver histology in chronic hepatitis C, with serum alanine transaminase levels persistently upto twice the normal range, and to identify factors associated with minimal and clinically significant histological disease categories. METHODS: This study was carried out at Ziauddin University Karachi and Pakistan Medical Research Council, Karachi, from January 2007 to July 2009. Biopsy specimens were staged and graded according to METAVIR scoring system. A fibrosis score of > or = F2 and activity score of > or = A2 was considered significant. Overall disease severity groups; minimal disease (less than F2 and A2) and significant disease (F2 or A2 and above), were compared for their association with different variables. RESULTS: Out of 83 patients, 32 had significant fibrosis and 15 had significant activity. Twenty three patients with significant fibrosis belonged to F2 stage. Nine had F3 fibrosis and none of our patients had cirrhosis. Overall 33 (40%) patients had significant disease. Age of the patient, alanine transaminase levels, number of the portal tracts and severity of the portal inflammation in liver biopsy were significantly associated with severity of the liver disease. Gender of the patient and steatosis in liver biopsy were not significant. CONCLUSION: A substantial proportion of patients with alanine transaminase levels within twice the upper limit of normal had significant liver disease.

Potential Utility of Cell Free High Mobility Group AT-hook 2 (HMGA2) as a Prognostic Biomarker in Liquid Biopsies of Oral Squamous Cell Carcinoma.

BACKGROUND: Locoregional spread is a frequent finding in oral cancer which dictates poor prognosis. HMGA2 expression has been linked to malignant traits of oral cancer in tissue biopsies however, data on HMGA2 expression in liquid biopsies in oral cancer is sparse. Purpose of this study was to explore prognostic relevance of HMGA2 in liquid biopsies of oral cancer patients. PATIENTS AND METHODS: After obtaining approval from Institutional Review Board of Ziauddin University and informed written consent from study subjects, expression of circulating HMGA2 was evaluated in 96 OSCC cases and 100 age and sex matched controls via real time PCR using specific set of primers. We further analyzed relationship of various sociodemographic and clinicopathological variables with HMGA2expression and explored its prognostic potential. RESULTS: Expression was seen in 22 (23%) cases. A higher expression was observed among subjects with local invasion (52.6% vs 47.4 %), distant metastasis (71.4% vs 28.6%) and tumor recurrence (57.1% vs 42.9%) p.

Antihepatotoxic activity of Saussurea lappa extract on D-galactosamine and lipopolysaccharide-induced hepatitis in mice.

The effects of aqueous-methanol extract of Saussurea lappa Clarke root (Sl.Cr) was investigated against D-galactosamine (D-GalN) and lipopolysaccharide (LPS)-induced hepatitis in mice. Co-administration of D-GalN (700 mg/kg) and LPS (1 microg/kg) significantly raised the plasma transaminase levels (ALT/AST) as compared to the control group (p < 0.05). Pretreatment of mice with different doses of Sl.Cr (150, 300 and 600 mg/kg) significantly prevented the D-GalN and LPS-induced rise in plasma levels of ALT and AST in a dose-dependent manner (p < 0.05). Post-treatment with Sl.Cr (600 mg/kg) significantly restricted the progression of hepatic damage induced by D-GalN and LPS (p < 0.05). The improvement in plasma enzyme levels was further verified by histopathology of the liver, which showed improved architecture, absence of parenchyma congestion, decreased cellular swelling and apoptotic cells in treatment groups as compared to the toxin group of animals. These data indicate that the Sl.Cr exhibits hepatoprotective effect in mice and this study rationalize the traditional use of this plant in liver disorders.

Association of visfatin with chronic kidney disease in a cohort of patients with and without diabetes.

OBJECTIVE: To evaluate association of serum visfatin with CKD secondary to diabetic nephropathy and to compare it with patients of CKD secondary to other risk factors. METHODS: Seventy eight individuals including 28 healthy controls and 50 patients of CKD were included in this study. Patients with CKD were further grouped based on etiology of CKD into diabetics and non-diabetics. Patients with type 1 diabetes mellitus, urinary tract infection, urolithiasis, liver cirrhosis, stroke, ischaemic heart disease, and rheumatoid arthritis were excluded. Measurement of Serum visfatin was done through EIA Kit (Phoenix pharmaceuticals Burlingame CA). RESULTS: Visfatin concentration was significantly high in patients with CKD compared to controls (8.7 +/- 4.7 vs. 5.2 +/- 3.3 p = 0.001). No significant difference in Visfatin concentrations between patients of CKD with and without diabetes was detected (9.2 +/- 5.5 vs. 8.3 +/- 3.2 p = 0.694). A significant negative correlation of visfatin with estimated GFR (r2= -0.383, p = 0.01) and a positive correlation with degree of proteinuria (p = 0.01) was observed. CONCLUSION: The present study confirms the association of visfatin with CKD, however further studies at molecular level to check its expression within renal tissue may clarify its definitive role in CKD

Ductal variant of prostate adenocarcinoma harbor Xenotropic murine leukemia virus related virus (XMRV) infection: a novel finding in subtype of prostate cancer.

OBJECTIVE: Xenotropic murine leukemia virus related virus (XMRV), is the first gammaretrovirus identified a decade ago, in human tissue bearing adenocarcinoma of prostate, followed by several researches documenting little or no prevalence of XMRV in prostate cancer samples. However, the status of XMRV within subtype of prostate adenocarcinoma has not been investigated yet. In this study, we investigated the relationship between XMRV and broad spectrum morphological entities of prostate adenocarcinoma, including acinar, ductal and other rare subtypes. MATERIAL AND METHODS: The prevalence of XMRV DNA in different histological subtypes of prostate adenocarcinoma was examined after characterizing the tumors into groups, using formalin-fixed, paraffin-embedded tissue samples from newly diagnosed prostate adenocarcinomas and archival prostate cancer tissue from our XMRV case control analysis. Broad-spectrum XMRV DNA amplification was performed by end-point polymerase chain reaction, using commercially available primer set. RESULTS: The study included 100 patients with prostate cancer. XMRV DNA was detected in 4 of 8 (50%) ductal adenocarcinomas, exhibiting papillary and cribriform histological features. XMRV DNA was not detected in any other variant of adenocarcinoma including acinar (0/91) and mucinous carcinomas (0/1). Majority of XMRV positive cases were biologically aggressive and present cancer at an early age upon diagnosis. CONCLUSION: Ductal adenocarcinomas demonstrate a significant association of XMRV DNA while other histological variants of prostate adenocarcinoma seem unrelated to XMRV infection.

Serum Metabolomic Profiles for Breast Cancer Diagnosis, Grading and Staging by Gas Chromatography-Mass Spectrometry.

Detection of metabolic signature for breast cancer (BC) has the potential to improve patient prognosis. This study identified potentially significant metabolites differentiating between breast cancer patients and healthy controls to help in diagnosis, grading, staging and determination of neoadjuvant status. Serum was collected from 152 pre-operative breast cancer (BC) patients and 155 healthy controls in this case-controlled study. Gas chromatography-mass spectrometry (GC-MS) was used to obtain metabolic profiles followed by chemometric analysis with the identification of significantly differentiated metabolites including 7 for diagnosis, 18 for grading, 23 for staging, 15 for stage III subcategory and 10 for neoadjuvant status (p-value < 0.05). Partial Least Square Discriminant Analysis (PLS-DA) model revealed a distinct separation between healthy controls and BC patients with a sensitivity of 96% and specificity of 100% on external validation. Models for grading, staging and neoadjuvant status were built with Decision Tree Algorithm with predictive accuracy of 71.5%, 71.3% and 79.8% respectively. Pathway analysis revealed increased glycolysis, lipogenesis, and production of volatile organic metabolites indicating the metabolic alterations in breast cancer.

Do VDR Gene Polymorphisms Contribute to Breast Cancer?

Breast cancer is the first or second leading cancer among females across the globe. A large number of studies have been conducted to assess any relationship between vitamin D receptor (VDR) gene polymorphisms and breast cancer development. Epidemiological studies have indicated that ethnic traits exhibited by a group of people with a common ancestry and culture, alter the link between VDR gene and breast cancer. It has been hypothesized that VDR polymorphisms have the capacity to impact both on incidence of breast cancer occurrence and to predict its outcome. A survey was here conducted to assess and compare the impact of vitamin D receptor gene polymorphisms Fok1, Bsm1, Taq1, Apa1 and poly (A) on development of breast cancer. Information was obtained from electronic databases including PubMed and Google Scholar for articles published during the period from 1996 to 2015. This search was achieved by using the terms "genetics", "breast cancer", "VDR gene", "polymorphisms". However, due to inconsistent results, no conclusive statements could be presented about the significance of the VDR genotype as far as the development of breast carcinoma is concerned'.

Correlation of Hormone Receptor and HER2/neu Expression with Clinicopathologic Parameters in Primary Breast Tumors.

BACKGROUND: Breast cancer (BC) is a major health issue worldwide as well as in Pakistan. All women belonging to any race, ethnicity or lineage are in danger of developing breast cancer. Significant factors influencing the development of breast malignancies are the genetic background, environmental conditions, reproductive parameters, the consequences of female hormones both intrinsic and extrinsic, alteration of immune status, and biologic determinants. MATERIALS AND METHODS: Overall 150 biopsy proven patients were included in the study. Samples were submitted for histopathology and determination of estrogen and progesterone receptor expression and HER2/neu status. Associations with other characteristics like age, tumor stage, node involvement, histological grade were also studied. RESULTS: Mean age at presentation was 46.7 years. The majority had invasive ductal carcinoma, 100 (84.7%), and were in stage pT3, 54 (45.7%). Important relationships (P<0.05) were found among ER, PR positivity, and Her 2 neu overexpression. However, no noteworthy link was identified amongst ER, PR, Her 2 neu and tumor grade, stage, age, lymph node involvement except for the menopausal status. CONCLUSIONS: In summary, breast cancer patients featured an advanced stage of disease, more lymph node involvement, and moderately high grade tumors and with more estrogen, progesterone receptor and HER2 positive tumors.

Immunohistochemical study of progesterone receptors in thyroid gland.

OBJECTIVE: To determine the progesterone receptor status in thyroid gland. METHODS: This study was based on immunohistochemical staining of formalin fixed paraffin embedded tissues, for progesterone receptors, in 50 previously diagnosed cases of various thyroid lesions and surrounding normal thyroid tissue. RESULTS: Out of 50 cases, 8 were nodular goiter, 9 cases of adenoma, 19 papillary carcinoma, 10 follicular carcinoma and four cases were of medullary carcinoma. Surrounding normal tissue was available in 4 non-neoplastic and 21 neoplastic lesions. Overall male patients comprised 20% (10 cases) and females 80% (40 cases). Although a wide range of lesions in both the sexes including wide age range were available, none of our cases were positively stained for progesterone receptors. CONCLUSION: In contrary to earlier reports by immunohistochemical method using monoclonal mouse anti-PR antibody clone PgR 636, on formalin-fixed paraffin embedded thyroid tissues, the progesterone receptors were not detectable in our human samples. The effect of progesterone on thyroid gland may be an indirect one.

Estrogen receptors in human thyroid gland. An immunohistochemical study.

OBJECTIVE: Thyroid diseases affect women approximately 3 times more frequently than men. It has been suggested that the female sex steroids stimulate thyroid growth such as in the breast. Seventeen beta-estradiol, the major estrogen in the body acts via estrogen receptors (ER) present in the nucleus of the cell. The aim of the study is to determine the ER status in the thyroid gland tissues. METHODS: Our study was based on immunohistochemical staining for ER. Fifty previously diagnosed cases of various thyroid lesions were selected from the Surgical Pathology Records of Pathology Department, Basic Medical Sciences Institute, Jinnah Postgraduate Medical Center, Karachi, Pakistan between March and August 2000. The staining was performed on formalin-fixed paraffin embedded tissues using monoclonal anti-ER antibody (clone 1D5). Out of 50 cases, 8 were nodular goiter, 9 cases of adenoma, 19 papillary carcinoma, 10 follicular and 4 cases were of medullary carcinoma. Surrounding normal tissue was available in 25 (50%) cases, 4 non-neoplastic and 21 neoplastic lesions. Out of 50 cases, 10 (20%) were males and 40 (80%) were females, the youngest patient was a 14-year-old female and the eldest patient was a 56-year-old male. RESULTS: Despite the availability of normal thyroid tissue and a wide range of lesions, none of our cases showed positive staining. CONCLUSION: In contrary to many earlier reports by immunohistochemical method using monoclonal antibody (clone 1D5) on formalin-fixed paraffin-embedded thyroid tissues, the ER are not detectable. The effect of estrogen on thyroid gland may be indirect one.