Role Of Biological Markers Research Articles

Role of biological markers and CT severity score in predicting mortality in patients with COVID‑19: An observational retrospective study.

COVID-19 pandemic is a continuing ongoing emergency of public concern. Early identification of markers associated with disease severity and mortality can lead to a prompter therapeutic approach. The present study conducted a multivariate analysis of different markers associated with mortality in order to establish their predictive role. Confirmed cases of 697 patients were examined. Demographic data, clinical symptoms and comorbidities were evaluated. Laboratory and imaging severity scores were reviewed. A total of 133 (19.1%) out of 697 patients succumbed during hospitalization. Obesity was the most common comorbidity, followed by hypertension, diabetes, coronary heart disease and chronic kidney disease. Compared with the survivor patients, non-survivors had a higher prevalence of diabetes, chronic kidney disease and coronary heart disease, as well as higher values of laboratory markers such as neutrophil-lymphocyte ratio (NLR), D-dimer, procalcitonin, IL-6 and C Reactive protein (CRP) and respectively high values of imaging severity scores. Multivariate regression analysis showed that high values of the proposed markers and chest computerized tomography (CT) severity imaging score were predictive for in hospital death: NLR [hazard ratio (HR): 3.127 confidence interval (CI) 95: 2.137-4.576]; D-dimer [HR: 6.223 (CI 95:3.809-10.167)]; procalcitonin [HR: 4.414 (CI 95:2.804-6.948)]; IL-6 [HR: 3.344 (CI 95:1.423-7.855)]; CRP [HR:2.997 (CI 95:1.940-4.630)]; and CT severity score [HR: 3.068 (CI 95:1.777-5.299)]. Laboratory markers and imaging severity scores could be used to stratify mortality risk in COVID-19 patients.

The role of inflammation on the association between apathy and motoric‐cognitive outcomes

AbstractBackgroundRecent literature indicates that apathy is associated with poor cognitive outcomes in community dwelling older adults, including motoric cognitive risk syndrome (MCR), a predementia syndrome defined by subjective cognitive complaints and slow gait. The role of biological markers in the association between apathy and motoric‐cognitive outcomes has not been established. The objectives of this study were to 1) examine the association between inflammation and apathy and 2) to evaluate the moderating effect of inflammation on the association between apathy and motoric‐cognitive outcomes.MethodWe measured apathy in 347 community dwelling older adults enrolled in the Central Control of Mobility in Aging study using an apathy scale score derived from confirmatory factory analysis of the Geriatric Depression Scale Long Form. We conducted cross‐sectional analyses of the following: the association between IL‐6 and CRP with apathy and the moderating effect of IL‐6 on the association between apathy and MCR and slow gait, using logistic regression and linear regression models, respectively. Linear associations were reported using β‐coefficients, while logistic associations were reported using odds ratio (OR) with 95% confidence intervals (CI), adjusting for age, gender, general health status and depression scale score.ResultlogIL‐6 but not logCRP was associated with apathy, in adjusted models (β=.037, 95% CI: .002‐.072, p=.04). Apathy was not significantly associated with MCR at cross‐section (OR: 0.48, 95% CI: .08‐2.97, p=.43), but apathy was significantly associated with gait velocity (β=‐14.45, 95% CI: ‐24.89 ‐ 4.01, p=.01). IL‐6 was associated with gait velocity (β=‐4.48, 95% CI: ‐7.42 ‐ 1.53, p=.003) and moderated the association between apathy and gait velocity by a change in β of 14.5%.ConclusionWe found that IL‐6, but not CRP was associated with apathy in a cohort of community dwelling older adults. Furthermore, IL‐6 moderated the association between apathy and gait velocity, a risk factor for dementia. Apathy was not associated with MCR at cross‐section, despite being associated with incident MCR in prior studies, suggesting that apathy is an early predictor of motoric‐cognitive decline.

Interval normobaric hypoxic therapy as a method of correction in neurological patients

This article is devoted to the analysis of modern literature on the use of interval normobaric hypoxic therapy among neurological patients. Its relevance is determined by the need to find measures to prevent the negative effects of oxygen deficiency, as hypoxia is a key factor in the development of many pathological conditions in the human body and in the central nervous system in particular. Hypoxic effects of excessive strength or duration, leads to decompensation of adaptation mechanisms, triggers a chain of irreversible metabolic disorders that lead to cell death, destruction of intercellular and neural network interactions in the brain and, consequently,to the development of neurological deficit and disability ofthe patient.However,when the body adapts to hypoxia,which can be achieved by using interval normobaric hypoxic therapy, it is possible to achieve a positive effect in the correction of patients with various diseases of the central nervous system. We have considered both general mechanisms of the body’s defense formation during adaptation to hypoxia, and individualmechanisms related directly to the central nervous system. The role of biologicalmarkers and markers of oxidative stress determining the body’s individual response to oxygen deficiency has been evaluated. An analysis of studies evaluating the effect of interval normobaric hypoxic therapy on the course of such diseases as Alzheimer’s disease, Parkinson’s disease, discirculatory encephalopathy and the consequences of craniocerebral injuries was performed. It was found that properly performed interval normobaric hypoxic therapy contributes to the correction and compensation of impaired functions, improves the quality of life of patients and increases the adaptive reserve of the body to stressful influences.

In(s) and out(s) of adolescent depression – Trajectories of development and recovery

While the role of biological markers in understanding major depressive disorder (MDD) in adults have been studied extensively, less has been done to identify the biomarkers of MDD development and recovery in adolescence. With the majority of mental health disorders starting in adolescence, identifying biomarkers of transition and recovery from MDD early in life is critical for developing effective prevention strategies. Considering most of the child and adolescent populations come from low-and-middle-income countries (LMICs), it is vital to focus on adolescent populations in these settings. With most studies coming from high-income countries (HICs), evidence suggests that elevated morning cortisol levels including cortisol awakening response (CAR), increased peripheral inflammation and brain abnormalities such as cortico-limbic dysregulation or blunted activity in reward related regions in response to positive information are associated with MDD and being at-risk for MDD development in adolescence. We also find that some of the biological mechanisms of recovery from MDD, mainly normalisation in the cortico-limbic dysregulation, are reported following psychological therapy, suggesting shared pathways leading to MDD vulnerability and recovery. Although, only a few studies include adolescent populations. Understanding molecular mechanisms through which psychological interventions are effective, as well as molecular markers of transition to depression in individuals at-risk, are important to inform effective prevention and intervention strategies.

CD117/c-KIT Expression in Phyllodes Tumor of the Breast and Its Correlation With Morphology and Clinical Outcome.

IntroductionBreast phyllodes tumor’s (PT) clinical behavior is difficult to predict on histology. There is limited amount of data available on the role of biological markers. The objective of this study was to assess the expression of CD117 (c-KIT) in PT of the breast and its relationship with morphology and clinical outcome.MethodsA total of 78 patients having available clinical records between 2004 and 2014 with breast PT were retrieved from the cancer registry at Shaukat Khanum Memorial Cancer Hospital and Research Centre, Lahore and were followed up. Immunohistochemical studies were performed on all the cases using mono­clonal antibody CD117 (DAKO A4502) using Leica Bond-Max automated biosystem (Leica Biosystems, Melbourne, Australia). Staining proportion and intensity of both epithelial and stromal elements were analyzed. Evaluation of the protein expression was determined and scored.ResultsPatients’ mean age was 45.13 ± 11.4 years. Thirty-nine (50.0%) patients had tumor on right side, 38 (48.7%) had on left and only one (1.3%) was bilateral. Thirty-two (41.0%) patients had benign PT, 21 (26.9%) had borderline and 25 (32.1%) had malignant PT. Negative CD117 expression was observed in 20 (62.5%), eight (38.0%) and 12 (48.0%) of benign, borderline and malignant PTs, respectively. Positive CD117 expression was observed in 12 (37.5%) benign, 13 (61.9%) borderline and 13 (52.0%) malignant PTs. There was insignificant association between CD117 expression with respect to tumor sub-type, patient’s age and clinical behavior (p-value > 0.05).ConclusionCD117 expression was not found to be associated with tumor type and was not associated with increased risk of recurrence in this sample of patients. Further work is needed to better understand the prognostic value of CD117 expression in breast PTs.

The role of biological markers in predicting infertility associated with non-obstructive endometriosis.

Our study evaluates if the use of biological markers can predict the infertility in women with non-obstructive endometriosis. Two prospective, non-randomised studies were conducted to identify if CA-125, IL-6 and IL-8 can be used as predictive markers for infertility in women with non-obstructive endometriosis. Peripheral levels of CA-125, IL-6 and IL-8 were measured before laparoscopy in all patients. We found a total number of 152 patients with non-obstructive endometriosis, we divided them in two groups: fertile and infertile women. There was a statistically significant difference of the mean of CA-125 values between the two groups (p = 0.00). The patients with infertility had a significantly higher IL-6 serum values than the fertile patients (p = 0.00). Regarding the IL-8 serum values, there was no statistically significant difference between the two groups fertile vs infertile, (p = 0.06). The elevated serum levels of CA-125 and IL-6 was associated with an increased probability of being diagnosed with infertility. The IL-8 had no value in predicting infertility associated with non-obstructive endometriosis.

Prognostic role of biological markers of bone metabolism in patients with coronary artery disease after coronary artery bypass grafting

Prognostic role of biological markers of bone metabolism in patients with coronary artery disease after coronary artery bypass grafting

Oxidative stress, aesthetics and ozone therapy: the role of biological markers [abstract

The redox system, that includes both reactive oxidising species (ROS) and antioxidants (AOs), play an unique role in the maintenance and in the promotion of wellness of all tissues and organs including skin and subcutaneous being related through the so called “eu-oxidative stress” to all basic processes of life i. e. the flow energy and information (1). Any disturbance of such system can lead to the “oxidative di-stress syndrome”, that is believed co-responsible not only of early aging but also of at least one hundred diseases including cardiovascular diseases, neurodegenerative disorders and cancer (2, 3).
 Oxidative di-stress is also involved in the pathophysiology of aesthetic as well as dermatological diseases like photo-aging, wrinkles, cellulite, and delayed wound healing (4). Unfortunately oxidative stress does not show any specific clinical picture but can be diagnosed only by means of specific biochemical tests on biological fluids (5). This approach led to the development of new branch of applied biochemistry and molecular diagnostics called Redoxomics (6).
 Redoxomics is a novel branch of “applied biochemistry” and “molecular diagnostics” having the following aims: i) to analyse the structure, the physiological role and the distribution of OCS and antioxidant systems in a living organism; ii) to identify the reciprocal interactions of oxidant and antioxidant systems – in the general flow of information – in a biological system (cell, tissue, organ, apparatus, system, whole organism) in a defined step of its development, in basic conditions as well as after potentially stressful stimuli; iii) to evaluate the implications of these findings by the view-point of epidemiology, patho-physiology, clinics, pharmacology and so on (6).
 On the basis of a Redoxomics profile the clinicians as well as the surgeons can identify early this new syndrome and to fight it by using not only more properly the conventional strategies but also new approach based on lifestyle changes (3), physiological redox modulators (7), biocompatible biomaterials (e. g. threads) (8, 9), gases (e. g. oxygen infusion/propulsion, carboxy therapy, ozone therapy) (10) which action is aimed to modulate the redox system function. Indeed the maintenance of a optimal oxidative balance is becoming one of the true pre-requisite “to be beautiful on the outside and on the inside”.

Microvesicles of leukocyte origin

Microvesicles are a new field of biological research. They are subcellular structures ranging in size from 100 to 1000 nm and found in practically all human biological fluids. Their sources are different cells. Microvesicles have a diverse internal composition and carry a wide spectrum of molecules on their surface, which determines their participation in physiological and pathological processes. Their assumed role of biological markers of diseases has aroused great interest. At the present time, there is a lot of data in the world literature about microvesicles of platelets and endothelial cells, and there is practically no data about microvesicles of leukocytes. In this regard, the purpose of the given review was to summarize the data about microvesicles of leukocytes. The review presents data about source cells, internal and superficial composition of leukocytes’ microvesicles, their interaction with various cells, and involvement in physiological and pathological processes. Further study of microvesicles will make it possible to clarify their role in normal and pathological conditions, the possibility of using them as vectors of diseases and carriers of various biologically active molecules.

Up-to-date clinical approaches of biomarkers’ use in heart failure

Heart failure (HF) is considered a leading cause of death in patients with established cardiovascular (CV) and metabolic diseases. Although current treatment strategy has improved survival rate and clinical outcomes of HF, the HF prevalence exhibits growth especially in older patients’ population and survivors after coronary atherothrombotic events. Current clinical guidelines regarding treatment and prevention of HF claim the role of biological markers as pretty easy and powerful tool for diagnosis, risk stratification, and prognostication of HF. However, there is not clear whether all these biological markers are able to equally predict CV death and HF-related outcomes in patients with acute and chronic HF as well as in various phenotypes of HF. The aim of the review is to discuss a role of in risk stratification and individual treatment in patients with different phenotypes of HF.

Biomarkers in Heart Failure

Heart failure (HF) is considered a leading cause of death in patients with established cardiovascular (CV) and metabolic diseases. Although current treatment strategy has improved survival rate and clinical outcomes of HF, the HF prevalence exhibits growth especially in older patients’ population and survivors after coronary atherothrombotic events. Current clinical guidelines regarding treatment and prevention of HF claim the role of biological markers as pretty easy and powerful tool for diagnosis, risk stratification, and prognostication of HF. However, there is not clear whether all these biological markers are able to equally predict CV death and HF-related outcomes in patients with acute and chronic HF as well as in various phenotypes of HF. The aim of the review is to discuss a role of in risk stratification and individual treatment in patients with different phenotypes of HF.

The Role of Biomarkers in Diverticular Disease.

Diverticulosis of the colon is a common condition in western countries. Acute diverticulitis may occur in 10% to 25% of the patients, sometimes associated with the presence of complications such as abscess, fistula, and perforation. Early diagnosis and accurate assessment of acute diverticulitis are necessary to start an efficacious treatment promptly, either conservatively or by surgery. The clinical picture may mimic other abdominal conditions; therefore, imaging techniques such as ultrasound or computed tomography are usually recommended, although they are expensive, examiner dependent, and potentially harmful. Recently, there has been increasing interest about the role of biological markers in diverticular disease as noninvasive, reliable, and inexpensive tools, conceivably able to support physicians in the diagnosis, the assessment of activity, and the monitoring of acute diverticulitis. By a MEDLINE search, most of the relevant data derived from C-reactive protein showed that it strongly supported the diagnosis of acute diverticulitis at values of >50 mg/L. It also represents a stronger marker compared with other serum biomarkers, able to correlate with the histologic severity in acute diverticulitis, the risk of perforation, and the response to therapy. Regarding fecal biomarkers, an interesting role has been reported for fecal calprotectin. It significantly correlates with inflammatory infiltrate. More relevantly, it correlates with the response to therapy and may predict the recurrence of colonic diverticulitis, as it is reliable in detecting subclinical intestinal inflammation, as reported already for inflammatory bowel disease. These represent encouraging results, but need to be confirmed in further larger studies.

Keratin 15, transcobalamin I and homeobox gene Hox-B13 expression in breast phyllodes tumors: novel markers in biological classification

Breast phyllodes tumors are rare neoplasms which present challenges for histological classification. Microscopic features are not always predictive of clinical behavior, and scarce data exist on the prognostic role of biological markers. Our study evaluated a series of 145 phyllodes tumors diagnosed at the Department of Pathology, Singapore General Hospital between 2006 and 2009, incorporating 91 (62.8%) benign, 40 (27.6%) borderline, and 14 (9.7%) malignant phyllodes tumors.

Conservative Management and Survival of Patients Affected by T1G3 Bladder Tumours. When Shall we Indicate it and When the Cystectomy?

Introduction Conservative management is not applicable to all T1G3 tumors. The appropriate treatment should minimize mortality while assuring reduced morbidity and good quality of life. Several attempts have been done to identify categories of T1G3 patients at higher risk. The role of biologic markers is unclear and the prognostic risk factors are mainly clinical. The proper time to abandon the conservative approach in favor of cystectomy is still object of debate. Objectives The aim of the present study is to assess the clinical tumor features showing a detrimental effect on survival, identify the clinical risk factors impacting survival in patients undergoing conservative management of T1G3 bladder tumor, and to analyze the prognostic role of recurrence. Methods The present analysis is extended to 236 patients with T1G3 bladder tumors treated by TUR plus intravesical therapy between 1976 and 2005. Patients with previous T1G3, Tis, more than 3 tumors or greater than 3cm were excluded. Urinary cytology was obtained within 30 days after TUR. Since 2000 re-TUR has been performed. A sequential combination of mitomycin-C (30mg/30ml) and epirubicin (50mg/50ml) was adopted in 106 patients (44.9%). BCG or other agents were given intravesically in 85 (36.0%) and 38 (16.1%) patients, respectively. Seven (3%) patients refused intravescical therapy. In the case of Ta-T1 recurrence, TUR and one year of adjuvant intravesical therapy were repeated. Patients went off study if Tis, T1G3 or T-category tumor over T1 were detected. Age, previous history, number of tumors, re-TUR, adjuvant therapy, recurrence and progression were considered for survival analysis. Results Tumors were primary in 177 (75.3%) and single in 144 (61.5%) cases. At a mean follow-up of 52 months (range: 3–246 months), 116 patients (49.2%) relapsed. The recurring tumor was T1 in 47 (40.5%) cases and T1G3 in 33 (28.4%). In 11 additional patients (9.5%) a Tis was detected. Twenty-five patients (10.6%) progressed and 15 patients (6.4%) underwent cystectomy. Median overall survival was 167 months. The 5-year progression-free survival rate was 87.8%. Thirty-two patients (13.6%) died, 22 (9.3%) for bladder cancer. A higher mortality was detected in recurrent (p= 0.002) and multiple (p=0.009) tumors undergoing conservative management. Survival was decreased by NMI recurrence (p<0.0001) and by progression (p=0.009). No statistical significant difference in survival was evident in relation to the grade and stage of the recurrent tumor. Conclusions Previous positive history and multiplicity are relevant risk factors for survival in patients affected by T1G3 NMI TCCB conservatively treated. Survival is decreased if conservative management is not given up at the time of NMI recurrence, independently from its grade and stage.

An approach to malignant mammary phyllodes tumors detection

Mammary phyllodes tumors (MPT) are uncommon fibroepithelial (biphasic) neoplasms whose clinical behavior is difficult to predict on the basis of histological criteria only. They are divided into benign, borderline malignant and malignant groups. Sometimes it appears difficult to distinguish these tumors from other types of soft tissue sarcomas. Because of the relatively scant data on the role of biological markers in MPT histogenesis, we have decided to undertake the following study, trying to shed more light on the issue by investigating the following elements that make up MPT: their histological patterns, biological behavior, enzymohistochemical, histochemical and immunohistochemical characteristics (ICH) together with the mast cell analysis. We examined the biopsy material of 35 MPT in our laboratory. Enzymohistochemistry was performed on frozen sections (method of Crowford, Nachlas and Seligman). The used methods were classical hematoxylin-eosin (H & E); histochemical Massontrichrome, Alcian-blue, Periodic acid Schiff and immunohistochemical LSAB2 method (DacoCytomation). Ki-67, c-kit, vimentin, estrogen receptor (ER), progesterone receptor (PR) and Her-2 oncoprotein immunohistochemistry was performed on all tumors. The patients were ranged per age from 30--62 years (mean 43.3 years, median 39 years). A total of 35 cases of MPT were included: 20 benign (57%), 6 borderline malignant (17%) and 9 malignant (26%). Twenty-two patients (62.8%) underwent segmental mastectomy, while 13 (37.2%) had total mastectomies. Twenty-eight patients had negative surgical margins at original resection. The mean size of malignant MPT (7.8 cm) was larger than that of benign MPT (4.5 cm). Significant features of the malignant MPT were: stromal cellularity, stromal cellular atypism, high mitotic activity, atypic mitoses, stromal overgrowth, infiltrative tumor contour and heterologous stromal elements. Benign MPT showed strong enzymohistochemical Leucine Amino Peptidase (LAP) activity in both epithelial and stromal components while it was weak or absent in the epithelial parts of the malignant tumors. Acid mucopolysacharides were present in the stromal component of all types of these tumors. Benign MPT had a lower Ki-67 than did borderline malignant MPT (4 versus 28). Malignant MPT had a greater than 8-fold higher Ki-67 activity than did benign tumors (35 versus 4). Intracyto-plasmatic c-kit expression was associated with a pathological diagnosis of malignant MPT, correlating with increasing grade (p < 0.05). In hypercellular stroma of borderline malignant and especially malignant forms of MPT, high activity of ER in mast cells was confirmed. Oncoprotein Her-2 activity, mostly in epithelial components, correlated with the degree of malignant progression of MPT (p < 0.05). Besides the well-known malignant features additional parameters have been found to be high Ki-67 and c-kit stromal expressions, and weak LAP activity in the epithelial part of malignant MPT, as well as mast cells with a high expression of ER.

Expression of basal keratins and vimentin in breast cancers of young women correlates with adverse pathologic parameters

Previous studies have suggested that breast cancer in young women has more aggressive biological features and poorer prognosis. However, the role of biological markers in these patients is not well understood. We aimed to learn more about this disease in a cohort of 125 young women from Singapore, Japan and Hong Kong, aged 35 years or less, with invasive breast cancer by evaluating the expression of vimentin and the basal cytokeratins CK14, CK5/6 and 34βE12. Both standard paraffin sections and tissue microarrays were used in the immunohistochemical evaluation of expression patterns of these four biological markers. CK5/6, CK14, vimentin and 34βE12, in increasing order of proportion, were detected in invasive carcinomas. Basal cytokeratins and vimentin showed significant inverse relationship with estrogen and progesterone receptor status while CK14 expression was found to be directly associated with c-erbB2 status. Basal cytokeratins and vimentin immunoreactivities were directly associated with CD117 and EGFR expression. Vimentin and 34βE12 immunopositivity correlated with tumor size, while vimentin was associated with higher histological grade. Our findings are in concert with reports that expression of basal cytokeratins and vimentin is correlated with adverse pathological parameters.

An evaluation of changes in biological markers (ER, PgR, or Ki67) after neoadjuvant chemotherapy (ET: epirubicin and docetaxel) in operable breast cancer

10613 Background: Neoadjuvant chemotherapy (NAC) is a valid option not only for advanced breast cancer but also for operable breast cancer. It was reported that disease-free and overall survival after NAC were equivalent to those after adjuvant therapy. The role of biological markers for the prediction of NAC may be evaluated using pathological responsiveness. In this study, we investigated the changes in biological markers such as estrogen receptor (ER), progesterone receptor (PgR), or Ki67 after NAC. Methods: Eligible patients (pts) were newly diagnosed with large primary tumors &gt; 3 cm or positive nodes. Fifty-two pts were enrolled and received epirubicin 60 mg/m2 followed by docetaxel 60 mg/m2 every 3 weeks for 4 cycles before surgery. In 51 cases out of the pts, pre-treatment needle biopsies and surgical specimen were analyzed for expression of ER, PgR, Her-2/neu, p53 and Ki67 by immunohistochemistry, and these data were compared to the pathological response. The pathological response was evaluated using the criteria of Japan Breast Cancer Society. Results: The median age was 47 (range, 29–67) and the mean tumor size was 5.2cm (range, 1.5–14.5). The clinical response was 86%; the BCS rate was 73% and pathological response was 31% including 3 cases with pCR. Regarding changes in biology after NAC, an average rate of ER positive cells significantly fell in 37% from 47% and that of PgR positive cells also fell in 14% from 32%. Most of cases, whose tumors were changed to ER/PgR negative from ER/PgR positive, were premenopausal women accompanied with amenorrhea during the treatment. Patients with lower ER, PgR, or a higher proliferation had a significantly greater benefit from NAC. The overexpression of Her2 was not correlated to pathological response, while p53 staining had a predictive value. And patients with positive nodes had a significantly favorable disease-free survival. Conclusions: The clinical effect of NAC (ET regimen) and the BCS rate by NAC were high. Although the rates of ER and PgR positive cells and proliferation were significantly reduced by NAC, a lower ER, PgR, or a higher proliferation might reflect a good pathological response. A negative change of ER or PgR by NAC might correlate with amenorrhea in premenopausal pts. No significant financial relationships to disclose.

P53 and c-kit (CD117) protein expression as prognostic indicators in breast phyllodes tumors: a tissue microarray study

Breast phyllodes tumors are fibroepithelial neoplasms whose clinical behavior is difficult to predict on histology. There is relatively scant data on the role of biological markers. In this study, we determined if p53 and CD117 (c-kit) protein expression was predictive of behavior in a series of 335 phyllodes tumors diagnosed at the Singapore General Hospital, using immunohistochemistry on tissue microarrays. Representative areas from 250 (75%) benign, 54 (16%) borderline and 31 (9%) malignant phyllodes tumors were selected for construction of tissue microarrays using the 2 mm punch. Immunohistochemistry for p53 and CD117 was carried out using the streptavidin–biotin method. Staining proportion and intensity of both epithelial and stromal elements were analyzed. p53 immunostaining was observed in the epithelium of 28 (10%) of 278 microarrays; myoepithelium of 53 (21%) of 251 microarrays; and stromal cells in 105 (36%) of 289 microarrays. CD117 immunohistochemical reactivity was noted in epithelial and stromal components of 175 (of 267, 66%) and 17 (of 273, 6%) microarrays, respectively. Stromal p53 and CD117 protein expression was associated with tumor grade (P<0.05). Of 43 (13%) women who suffered recurrences during the follow-up period, CD117 stromal staining predicted recurrent disease (P<0.05), but p53 was not correlative. We conclude that tissue microarrays are a convenient method for evaluating immunostaining results of large numbers of phyllodes tumors. Although positive p53 stromal immunohistochemical detection may corroborate histologic malignancy, it is CD117 protein expression in phyllodes tumor stromal cells that may be of potential utility in predicting recurrent disease.

The crucial role of tumour specimen handling in childhood cancer outcomes

The significant advances achieved in the care of children with cancer have been the result of carefully conducted clinical trials in international cooperative group settings. Specialized biological testing of tumour specimens is now an essential component of risk and treatment assignment for many childhood cancers. Thus, the appropriate collection and handling of tumour specimens is crucial to maintaining and further advancing the excellent outcomes that we have achieved. We recommend that all children with a strongly suspected malignancy, or cases in which the situation is unclear, be discussed with a paediatric oncologist before obtaining a tumour specimen. When a tumour is discovered incidentally at surgery, we recommend that the tumour be placed in a saline-soaked gauze and a paediatric pathologist or oncologist contacted immediately. Further progress in understanding and treating childhood cancer is intimately linked to basic studies of biology, translational research and determining the role of biological markers in risk stratification. Early and careful collaboration between front-line physicians and tertiary care oncology specialists is essential to the continuing success of treatment of children with cancer.

Immunohistochemical Biomarkers in Patients with Early-Onset Breast Carcinoma by Tissue Microarray

Young women with breast cancer have a poor prognosis, and the role of biologic markers in young women is not well defined. We investigated the association of estrogen receptor, progesterone receptor, Bcl-2, HER-2/neu, p53, and Ki-67 with clinicopathologic features and outcome in young women with breast cancer. A cohort of 103 patients with early-onset breast cancer treated with conservative surgery and radiotherapy were entered in this study. Age range was 25-45 years, and median follow-up was 8.7 years. Each of the paraffin-embedded specimens was immunologically stained for six biomarkers expression by a recently developed tissue microarray method. The 10-year overall breast relapse-free and distant relapse-free survival rates were 82.7%, 84.6.4%, and 66.7%, respectively, with 14 local relapses and 26 distant metastases among the 103 patients evaluated. Positive expression of estrogen receptor, progesterone receptor, bcl-2, HER-2/neu, p53, and Ki-67 were 42.7%, 48.5%, 35.6%, 28.0%, 36.9%, and 39.7%, respectively. Tumor stage and nodal status were significantly associated with overall survival and distant metastasis-free rate in univariate and multivariate analysis. Progesterone receptor negativity and Ki-67 positivity were associated with distant metastasis. There was no statistically significant correlation between the six biomarkers and local relapse. Progesterone receptor, Ki-67, tumor stage, and nodal status were prognostic factors for distant failure in early-stage breast cancer in young patients. Further studies are needed to find other biologic markers associated with local failure in this group of patients.