Clinicopathological correlation of the expression of excision repair cross complementation group 1 (ERCC1) in oral cavity squamous cell carcinomas: an immunohistochemical study.

BACKGROUND: The nucleotide excision repair pathway is a sophisticated DNA repair mechanism that reduces DNA damage caused by exogenous factors. Excision repair cross complementation group 1 (ERCC1) is a prominent member of this pathway that maintains the genomic stability. The aim of this study is to determine the association between the immunohistochemical expression of ERCC1 and the clinical and pathological features of oral cavity squamous cell carcinomas. MATERIALS AND METHODS: The sections of formalin fixed paraffin embedded tissue blocks of oral squamous cell carcinomas (n = 60) were immunohistochemically stained with anti-ERCC1 antibody. The association between the nuclear expression of ERCC1 and the clinicopathological parameters of the tumors and the patient outcomes was evaluated using the chi-square test. RESULTS: ERCC1 expression was evident in all studied cases of the oral squamous cell carcinomas. A high ERCC1 expression was associated with smaller tumors, tumors without lymph node involvement and well-differentiated tumors (p < 0.001). Better outcomes were associated with higher expression of ERCC1 (p = 0.028). CONCLUSION: ERCC1 seems to be an efficient biomarker for prognostication of oral squamous cell carcinomas. High expression of ERCC1 indicates more favorable course of the disease.

The role of Ki-67, p16, CD34, Bcl-2, cyclooxygenase-2 in the pathogenesis of proliferative verrucous leukoplakia.

CONTEXT: Proliferative verrucous leukoplakia (PVL) is a highly persistent and aggressive oral pre-malignant lesion with an obscure etiopathogenesis and a malignant transformation rate of 85-100%. AIMS: The aim of the present study is to assess the role of Ki-67, p16, CD34, Bcl-2, cyclooxygenase-2 (COX-2) in the spectrum of PVL to ascertain their role in its etiopathogenesis. SETTINGS AND DESIGN: A retrospective chart analysis was carried out on a series of seven confirmed cases of PVL, which were followed-up for 2 years. SUBJECTS AND METHODS: Immunohistochemical appraisal of these cases was carried out by a panel of markers, related to cell proliferation, cell cycle regulation, angiogenesis, apoptosis and inflammation. The expression of these markers was correlated with patients' clinicopathological profile. STATISTICAL ANALYSIS USED: The frequency distribution of the group data was analyzed. RESULTS: The latest labeling index of Ki-67 in our cases ranged from 8.18 to 12.6. p16 was positive in 3/7 cases. Bcl-2 expression was moderately positive in 2/7 cases. All cases were intensely positive for COX-2 staining. Microvascular density assessed by CD34 staining ranged from 11 to 20/high power fields. One case which transformed into squamous cell carcinoma demonstrated increased Ki-67, Bcl-2, COX-2, CD34 expression, but negative p16 and Bcl-2 expression. CONCLUSIONS: Application of these markers in understanding the behavior of PVL suggests that an imbalance between the proliferation apoptosis dynamics of the lesion accompanied by an increase in inflammation and angiogenesis underlie the molecular pathogenesis of the PVL spectrum.

In vivo effects of Eurycoma longifolia Jack (Tongkat Ali) extract on reproductive functions in the rat.

An aqueous extract of Eurycoma longifolia (Tongkat Ali; TA) roots is traditionally used to enhance male sexuality. Because previous studies are limited to only few sperm parameters or testosterone concentration, this study investigated the in vivo effects of TA on body and organ weight as well as functional sperm parameters in terms of safety and efficacy in the management of male infertility. Forty-two male rats were divided into a control, low-dose (200 mg kg(-1) BW) and high-dose (800 mg kg(-1) BW) group (n = 14). Rats were force-fed for 14 days and then sacrificed. Total body and organ weights of the prostate, testes, epididymides, gastrocnemius muscle and the omentum were recorded. Moreover, testosterone concentration, sperm concentration, motility, velocity, vitality, acrosome reaction and mitochondrial membrane potential (MMP) were assessed. Whilst TA decreased BW by 5.7% (P = 0.0276) and omentum fat by 31.9% (P = 0.0496), no changes in organ weights were found for the prostate, testes and epididymides. Testosterone concentration increased by 30.2% (P = 0.0544). Muscle weight also increased, yet not significantly. Whilst sperm concentration, total and progressive motility and vitality increased significantly, MMP improved markedly (P = 0.0765) by 25.1%. Because no detrimental effect could be observed, TA appears safe for possible treatment of male infertility and ageing male problems.

Effect of Eurycoma longifolia Jack (Tongkat ali) extract on human spermatozoa in vitro.

Eurycoma longifolia (Tongkat ali; TA) is a Malaysian shrub used to treat various illnesses including male infertility. Considering that TA is used to improve male fertility and no report regarding its safety has been published, this study investigated the effects of TA extract on various sperm functions. Semen samples of 27 patients and 13 donors were divided into two groups, washed and swim-up spermatozoa, and incubated with different concentrations of TA (1, 10, 20, 100, 2000 µg ml(-1) ) for 1 h at 37 °C. A sample without addition of TA served as control. For washed spermatozoa, significant dose-dependent trends were found for vitality, total motility, acrosome reaction and reactive oxygen species-positive spermatozoa. However, these trends were only significant if the highest concentrations were included in the calculation. Contrary, the increase in the percentage of acrosome-reacted spermatozoa with increasing TA concentrations is very significant (P < 0.0001), and a significant difference (P = 0.0069) to the control could even be recorded at 20 µg TA per ml. For swim-up spermatozoa, no trend could be observed. Results indicate that the TA extract has no deleterious effects on sperm functions at therapeutically used concentrations (<2.5 µg ml(-1) ). However, at very high concentrations, TA may have harmful effects in vitro.

Molecular analysis of oral squamous cell carcinoma: a tissue microarray study.

BACKGROUND: An intriguing aspect of Oral Squamous Cell Carcinomas (OSCC) is its behavioral disparity. Among patients who present with the similar clinicopathological features, some have a better prognosis than others. Identification of molecular alterations responsible for this may contribute to a greater understanding of tumor behavior. Tissue microarray (TMA) approach is a high throughput technology that enables analysis of multiple molecular targets simultaneously without causing any morphological alteration to tissue specimens. AIM AND OBJECTIVE: To assess the tumor behavior based on the expression of p53, Bcl-2 and E-cadherin using TMA technology. SETTINGS AND DESIGN: This was a case series analysis using tissue microarray technology. MATERIALS AND METHODS: Formalin-fixed Paraffin-embedded (FFPE) tissue blocks of histological proven cases of OSCC (n = 30) were retrieved from the department archives. Tissue microarray blocks were constructed; 4 mum thick sections were cut and immunostained for p53, Bcl-2 and E-cadherin. STATISTICAL ANALYSIS: Mean (SD) was used to summarize age, frequencies with percentages was used to summarize categorical variable and Chi-square test was used to find association between histopathology evaluation and expression of Bcl-2, p53, E-cadherin. RESULTS AND CONCLUSION: Bcl-2 was the most frequently expressed biomarker. The expression of Bcl-2 was inversely related to the degree of differentiation (P = 0.005). The follow-up data showed that 63.6% of the cases that were positive for both Bcl-2 and E-cadherin were disease-free following treatment. Tissue microarray technology is a promising way to analyse multiple biomarkers simultaneously. The molecular data obtained from TMA will enhance diagnosis, provide better prognostication and will improve cancer treatment for individual patients.

Multicenter evaluation of the Cepheid Xpert methicillin-resistant Staphylococcus aureus (MRSA) test as a rapid screening method for detection of MRSA in nares.

The first U.S. multicenter clinical trial to assess the performance of the Cepheid Xpert MRSA assay (Xpert MRSA) was conducted. The assay is a qualitative test designed for the rapid detection of methicillin-resistant Staphylococcus aureus (MRSA) directly from nares swabs. This novel test combines integrated nucleic acid extraction and automated real-time PCR for the detection of a MRSA-specific signature sequence. A total of 1,077 nares specimens were collected from seven geographically distinct health care sites across the United States with prevalence rates ranging from 5.2% to 44%. Nares specimens were tested by (i) the Xpert MRSA assay, (ii) direct culture on CHROMagar MRSA medium (direct CM culture), and (iii) broth-enriched culture (Trypticase soy broth with 6.5% sodium chloride) followed by plating onto CHROMagar MRSA medium (broth-enriched CM culture). When direct CM culture was designated the reference method, the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of the Xpert MRSA assay were 94.3%, 93.2%, 73.0%, and 98.8%, respectively. When broth-enriched CM culture was used as the reference method, the clinical sensitivity, specificity, PPV, and NPV of the Xpert MRSA assay were 86.3%, 94.9%, 80.5%, and 96.6%, respectively. The BD GeneOhm MRSA (BDGO) assay was performed as a comparative molecular method. No statistical performance differences were observed between the Xpert MRSA and BDGO assays when they were compared to culture methods. From this large-scale, multicenter clinical comparison, we conclude that the Xpert MRSA assay is a simple, rapid, and accurate method for performing active surveillance for MRSA in a variety of health care populations.

Glandular odontogenic cyst. A rare entity with aggressive biological behaviour. A case report.

Glandular Odontogenic cyst is an apparently rare jaw cyst characterised by typical histopathological features, propensity to reach large size and high rate of local recurrence, if not adequately treated. Identification of this cyst as a separate entity is important because of the difference in biological behaviour. We report a case of Glandular Odontogenic cyst occurring in maxilla.

Age specific prostate specific antigen reference ranges: population specific.

PURPOSE: We determined whether 60 to 79-year-old men with a negative digital rectal examination and a serum prostate specific antigen (PSA) within age specific PSA reference ranges could safely forgo prostate biopsy. MATERIALS AND METHODS: We reviewed the medical records of all 60 to 79-year-old men at the Brooklyn Veterans Administration Medical Center who had a PSA assay, digital rectal examination and subsequent prostate biopsy for an abnormal rectal examination and/or PSA greater than 4.0 ng./ml. from January 1991 through August 1995. We compared our results using the standard reference range of 0 to 4.0 ng./ml. with those obtained had we used any of 4 different age specific PSA reference ranges. RESULTS: We performed 1,280 prostate biopsies in 1,046 men with available PSA and digital rectal examination data. Using age specific PSA reference ranges 73 of 1,280 biopsies (5.7%) would have been avoided. Of those 73 avoided biopsies 15 (20.5%) had cancer that would have gone undetected and 9 of 15 (60%) undetected cancers had unfavorable histology. Results were not statistically significantly different among the 4 age specific PSA reference ranges. Regarding race, cancer detection rates were significantly higher for black compared with white men but there was no statistically significant difference for missed cancers or missed cancers with unfavorable histology. CONCLUSIONS: In contrast to previous reports of unfavorable histological characteristics in only 5% of missed cancers using age specific PSA reference ranges, 60% of missed cancers in our patients exhibited unfavorable histology. We conclude that age specific PSA reference ranges did not safely eliminate the need for prostate biopsy in our study population. In 60 to 79-year-old men with a negative digital rectal examination we continue to use PSA greater than 4.0 ng./ml. as an indication for prostate biopsy.

Early prostate cancer detection and potential for surgical cure in men with poorly differentiated tumors.

OBJECTIVES: Long-term cure after radical prostatectomy has been reported for men with organ-confined poorly differentiated prostate cancer. However, organ-confined rates have been disappointingly low, ranging from 8% to 18% in earlier series, which have consisted primarily of patients not screened for prostate-specific antigen (PSA). Recently, it has been our impression that a greater number of patients with poorly differentiated tumors have had organ-confined disease than earlier reports would have led us to predict. METHODS: To test this hypothesis, we reviewed the results of surgical staging in men with poorly differentiated tumors (Gleason score 8 to 10) entered into our prospective data base between August 1992 and June 1996. RESULTS: Of 109 men undergoing operation during the study period, 64 underwent exploration for planned radical prostatectomy with no previous therapy and comprise the study cohort. In 92%, the initial presentation was an elevated PSA level (median 10.8 ng/mL). We observed an organ-confined rate of 30% and found preoperative PSA levels of 10 ng/mL or less to be a significant predictor of organ-confined disease (45% versus 17%, P = 0.016, chi-square test). On preliminary follow-up (median 31 months), 84% of men with organ-confined tumors are free of PSA relapse, similar to that seen in 233 men with organ-confined moderately differentiated tumors undergoing operation during the study period (P = 0.12, log-rank test). CONCLUSIONS: Early prostate cancer detection, as reflected by PSA levels of 10 ng/mL or less, is associated with a higher organ-confined rate in men with poorly differentiated tumors. On preliminary follow-up, PSA relapse rates were lower in men with pathologically confirmed, organ-confined, poorly differentiated disease.

In vitro activities of quinolones, beta-lactams, tobramycin, and trimethoprim-sulfamethoxazole against nonfermentative gram-negative bacilli.

From 1991 to 1995, 8,975 nonfermentative gram-negative bacilli were isolated from patients at The Ohio State University Medical Center: 71% Pseudomonas aeruginosa, 14% Stenotrophomonas maltophilia, 7.6% Acinetobacter baumannii, and < 2% each of 25 other species. The MICs of trovafloxacin (CP-99,219), ciprofloxacin, ofloxacin, ampicillin-sulbactam, piperacillin, piperacillin-tazobactam, ceftazidime, cefoperazone, ceftriaxone, imipenem, tobramycin, and trimethoprim-sulfamethoxazole (TMP-SMZ) were determined for 308 isolates, representing 13 species, by a standardized broth microdilution method. The activities of all drugs were species dependent. The fluoroquinolones had inconsistent activity against most species, although several relatively uncommon nonfermenters were consistently susceptible or resistant. Trovafloxacin was considerably more active than ciprofloxacin and ofloxacin against S. maltophilia, A. baumannii, and several less common species. Among the beta-lactams, relative activities varied considerably; overall, imipenem had the broadest spectrum of activity but was inactive against S. maltophilia and Burkholderia cepacia isolates. Tobramycin and TMP-SMZ had stereotypic spectra of activity. Tobramycin was active against most species except S. maltophilia, Alcaligenes xylosoxidans subsp. xylosoxidans, Burkholderia spp., and Weeksella virosa. TMP-SMZ was active against most species except P. aeruginosa and Pseudomonas fluorescens-putida. A review of laboratory records indicated few changes in susceptibility patterns from 1991 to 1995; the only clear trend was toward increasing P. aeruginosa resistance to all classes of drugs.