Search

Virus-specific T-cells (VSTs) from third-party donors mediate short- and long-term antiviral effects in allogeneic hematopoietic stem cell transplant (HSCT) recipients with relapsed or refractory viral infections. We investigated early administration of third-party VSTs, together with antiviral therapy in patients requiring treatment for first cytomegalovirus (CMV) or Epstein-Barr virus (EBV) infection. Thirty HSCT patients were treated with 1 to 4 VST infusions (2 × 107 cells/m2; CMV n=27, EBV n=3) at a median of 4 days after initiation of antiviral treatment. The overall viral response rate was 100%, with a complete response (CR) rate of 94%. Of the 28 patients who achieved a CR, 23 remained virus PCR negative (n=9) or below quantitation limit (n=14) for the duration of follow-up. Four patients had brief episodes of quantifiable reactivation not requiring additional therapy, and one required a second infusion after initial CR, remaining PCR negative thereafter. All 3 patients treated for EBV post-transplant lymphoproliferative disorder achieved sustained CR. Rates of aGVHD and cGVHD after infusion were 13% and 23%, respectively. There were no serious infusion-related adverse events. VST infusion was associated with rapid recovery of CD8+CD45RA-CD62L- and a slower recovery of CD4+CD45RA-CD62L- effector memory T-cells; CMV-specific T-cells comprised up to 13% of CD8+ cells. At 1 year post-transplant, non-relapse mortality was 10%, cumulative incidence of relapse was 7%, overall survival was 88% and 25 of 27 patients had ECOG status of 0 or 1. Early administration of third-party VSTs in conjunction with antiviral treatment appears safe and leads to excellent viral control and clinical outcomes. Registered on Australian New Zealand Clinical Trials Registry as #ACTRN12618000343202., (© 2022 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)

Chimeric antigen receptor (CAR)-T cell therapy is a genetically-modified cellular immunotherapy that has a current established role in the treatment of relapsed/refractory B-cell acute lymphoblastic leukaemia and diffuse large B-cell lymphoma, with emerging utility in a spectrum of other haematological and solid organ malignancies. It is associated with a number of characteristic toxicities, most notably cytokine release syndrome and neurotoxicity, for which laboratory testing can aid in the prediction of severity and in monitoring. Other toxicities, such as cytopenias/marrow hypoplasia, hypogammagloblinaemia and delayed immune reconstitution are recognised and require monitoring due to the implications for infection risk and prophylaxis. The detection or quantitation of circulating CAR-T can be clinically useful, and is achieved through both direct methods, if available, or indirect/surrogate methods. It is important that the laboratory is informed of the CAR-T therapy and target antigen whenever tissue is collected, both for response assessment and investigation of possible relapse, so that the expression of the relevant antigen can be assessed, in order to distinguish antigen-positive and -negative relapses. Finally, the measurement of circulating tumour DNA has an evolving role in the surveillance of malignancy, with evidence of its utility in the post-CAR-T setting, including predicting patients who will inevitably experience frank relapse, potentially allowing for pre-emptive therapy., (Copyright © 2021 Royal College of Pathologists of Australasia. Published by Elsevier B.V. All rights reserved.)

The ability to sensitively monitor minimal residual disease (MRD) has played a key role in improving the management and outcomes for a number of leukemias, particularly acute promyelocytic leukemia and childhood acute lymphoblastic leukemia. By contrast, MRD monitoring in acute myeloid leukemia (AML) has been limited by variable assay methodologies and a relative paucity of patient-specific MRD markers. Inter- and intratumor genetic heterogeneity poses significant challenges for the identification of molecular markers suitable for MRD monitoring in AML, particularly for those cases without structural chromosomal rearrangements associated with fusion genes. Furthermore, the need to discriminate which mutations may be suitable for MRD monitoring creates additional complexity. The mainstay of current molecular MRD monitoring is real-time quantitative PCR, targeting fusion genes, mutations, and gene overexpression. New technologies, particularly next-generation sequencing approaches, offer new ways to overcome these limitations. Here, the authors review the techniques available for molecular MRD monitoring in AML and discuss their utility in clinical practice., (Copyright © 2018 American Society for Investigative Pathology and the Association for Molecular Pathology. Published by Elsevier Inc. All rights reserved.)

Background: Ventilator-associated pneumonia (VAP) is a significant cause of morbidity and mortality, complicating the medical course of approximately 10% of mechanically-ventilated patients, with an estimated attributable mortality of 13%. To treat VAP empirically, the American Thoracic Society currently recommends antibiotic therapy based on the patients' risk of colonisation by an organism with multidrug resistance. The selection of initial antibiotic therapy in VAP is important, as inappropriate initial antimicrobial treatment is associated with higher mortality and longer hospital stay in intensive care unit (ICU) patients.While guidelines exist for the antibiotic treatment of hospital-acquired pneumonia (HAP) from the American Thoracic Society and the British Society for Antimicrobial Chemotherapy, there are many limitations in the quality of available evidence. This systematic review aimed to summarise the results of all randomised controlled trials (RCTs) that compare empirical antibiotic regimens for VAP., Objectives: The primary objective of this review was to assess the effect of different empirical antimicrobial therapies on the survival and clinical cure of adult patients with ventilator-associated pneumonia (VAP). Secondary objectives included reporting the incidence of adverse events, new superinfections, length of hospital stay, and length of intensive care unit (ICU) stay associated with these therapies., Search Methods: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, LILACS, CINAHL and Web of Science to December 2015; we searched ClinicalTrials.gov to September 2016., Selection Criteria: Two review authors independently assessed RCTs comparing empirical antibiotic treatments of VAP in adult patients, where VAP was defined as new-onset pneumonia that developed more than 48 hours after endotracheal intubation. Physicians and researchers were not required to be blinded for inclusion in this review., Data Collection and Analysis: Two review authors independently extracted study data. We pooled studies and analysed them in two ways. We examined monotherapy, or a single experimental antimicrobial drug, versus combination therapy, or multiple experimental antimicrobial drugs. We also examined carbapenem therapy versus non-carbapenem therapy., Main Results: We included 12 studies with 3571 participants. All included studies examined the empiric use of one antimicrobial regimen versus another for the treatment of adults with VAP, but the particular drug regimens examined by each study varied. There was potential for bias because some studies did not report outcomes for all participants. All but one study reported sources of funding or author affiliations with pharmaceutical companies.We found no statistical difference in all-cause mortality between monotherapy and combination therapy (N = 4; odds ratio (OR) monotherapy versus combination 0.97, 95% confidence interval (CI) 0.73 to 1.30), clinical cure (N = 2; OR monotherapy versus combination 0.88, 95% CI 0.56 to 1.36), length of stay in ICU (mean difference (MD) 0.65, 95% CI 0.07 to 1.23) or adverse events (N = 2; OR monotherapy versus combination 0.93, 95% CI 0.68 to 1.26). We downgraded the quality of evidence for all-cause mortality, adverse events, and length of ICU stay to moderate for this comparison. We determined clinical cure for this comparison to be of very low-quality evidence.For our second comparison of combination therapy with optional adjunctives only one meta-analysis could be performed due to a lack of trials comparing the same antibiotic regimens. Two studies compared tigecycline versus imipenem-cilastatin for clinical cure in the clinically evaluable population and there was a statistically significant increase in clinical cure for imipenem-cilastatin (N = 2; OR tigecycline versus imipenem-cilastatin 0.44, 95% CI 0.23 to 0.84). Of importance, this effect was due to a single study.We found no statistical difference in all-cause mortality between carbapenem and non-carbapenem therapies (N = 1; OR carbapenem versus non-carbapenem 0.59, 95% CI 0.30 to 1.19) or adverse events (N = 3; OR carbapenem versus non-carbapenem 0.78, 95% CI 0.56 to 1.09), but we found that carbapenems are associated with a statistically significant increase in the clinical cure (N = 3; OR carbapenem versus non-carbapenem 1.53, 95% CI 1.11 to 2.12 for intention-to-treat (ITT) analysis and N = 2; OR carbapenem versus non-carbapenem 2.29, 95% CI 1.19 to 4.43 for clinically evaluable patients analysis). For this comparison we downgraded the quality of evidence for mortality, and clinical cure (ITT and clinically evaluable populations) to moderate. We determined the quality of evidence for adverse events to be low., Authors' Conclusions: We did not find a difference between monotherapy and combination therapy for the treatment of people with VAP. Since studies did not identify patients with increased risk for multidrug-resistant bacteria, these data may not be generalisable to all patient groups. However, this is the largest meta-analysis comparing monotherapy to multiple antibiotic therapies for VAP and contributes further evidence to the safety of using effective monotherapy for the empiric treatment of VAP.Due to lack of studies, we could not evaluate the best antibiotic choice for VAP, but carbapenems as a class may result in better clinical cure than other tested antibiotics.

Cyclin D-1 protein over-expression and/or gene amplification have been shown to be frequent events in subsets of breast carcinomas. Cyclin D-1 is generally considered as a weak oncogene, and its over-expression has been shown to occur in occasional benign breast lesions. In a previous series, we have shown that cyclin D-1 was over-expressed in subsets of apocrine metaplasia (APM) and apocrine adenosis (AA) of the breast and that such over-expression was mostly associated with a significant increase in the proliferative capacity of these lesions. We examined the mechanisms involved in cyclin D-1 over-expression in apocrine lesions. A total of 41 cases were analysed in this study. The cases were divided into: 18 cases of APM and 23 cases of AA. All cases analysed had been previously analysed by immunohistochemistry, and all showed over-expression of the cyclin D-1 protein. Fluorescence in situ hybridisation (FISH) was performed using a dual cyclin D-1 (spectrum orange)/chromosome 11 centromere (spectrum green) DNA probe. The results showed that none of the cases studied had concomitant gene amplification. These results suggest that other post-transcriptional mechanisms might be responsible for cyclin D-1 protein over-expression in benign apocrine lesions. Further studies are needed to understand the mechanisms involved in abnormal cyclin D-1 expression in these lesions., (Copyright © 2010 Elsevier GmbH. All rights reserved.)

Apocrine metaplasia (APM) is a common finding in the breast of postmenopausal women and is seen in a broad spectrum of lesions ranging from microscopic cysts to invasive apocrine carcinoma. Apocrine metaplasia within sclerosing adenosis is known as apocrine adenosis (AA) and is considered a benign lesion of the breast. Apocrine metaplasia and AA have been the subject of many studies; however, little is known about the dynamics of cell turnover in these lesions. Recent studies have shown that some forms of AA may show altered degree of proliferation along with altered expression of bcl-2 and bax proteins. In the current study, we investigate further aspects of apoptosis to help understand the mechanisms of cell turnover in AA and APM. To investigate cell turnover in APM and AA, immunohistochemistry was used to study the expression of the apoptotic markers Bak, Mcl-1, Bcl-x, and Bcl-x(L) in 45 cases of APM (13 cases of nonpapillary APM, 21 cases of simple papillary APM, and 11 cases of complex papillary APM). Also, 34 cases of AA (23 cases of non-atypical AA [NAA] and 11 cases of atypical AA [AAA]) were included in the study. The expression of hTERT and the proliferation marker Ki-67 were also determined. The TdT-mediated dUTP nick-end labeling (TUNEL) technique was used to study the apoptotic status in 28 cases of APM (12 cases nonpapillary APM and 16 cases of papillary APM including simple and complex forms) and 22 cases of AA (15 cases of NAA and 7 cases of AAA). The results showed that all cases studied by immunohistochemistry were positive for the expression of Bak, Mcl-1, Bcl-x, and Bcl-x(L) showing a pattern of staining similar to that seen in the normal breast epithelium. There was no relation between hTERT positivity and the degree of proliferation in any of the lesions studied. The TUNEL results revealed an apoptotic index (AI) of 0.4% and 0.2% in the papillary and nonpapillary groups of APM, respectively. There was no statistical significance between the AI of these 2 groups and that of the normal breast epithelium (0.3%). The average Ki-67 index in the nonpapillary group was 0.7%, whereas in the papillary group, a value of 4% was recorded. In the cases of AA, an AI of 0.4% and 0.3% in NAA and AAA, respectively, was seen. There was no statistical significance between the AI of these 2 groups and that of the normal breast epithelium (0.3%). The Ki-67 index was 5.2% and 6.6% in the NAA and AAA, respectively. The current results show that apoptosis is not a common event in APM and AA even in the presence of increased proliferation, which may render some of these lesions more susceptible to oncogenic changes. Further studies are needed to study other apoptotic pathways that may be involved in cell turnover in these lesions., (2010 Elsevier Inc. All rights reserved.)

G1/S transition defects have been a proposed requirement for tumor development. Apocrine metaplasia (APM) in the breast has been held as a sign of benignity. Yet, a number of studies have reported the presence of molecular abnormalities in some forms of APM suggesting a possible oncogenic potential for some of these lesions. We currently investigate the role of some of the cell cycle proteins, previously reported to be de-regulated in breast cancer, in an attempt to assess their significance in APM. Using immunohistochemistry, the expression of cyclin D1, cyclin A, p27, p21, p16, pRb and Ki-67 was examined in 93 cases of APM. The cases were divided into nonpapillary (NAPM) (30 cases) and papillary metaplasia (PAPM) (63 cases). PAPM was further subdivided into simple papillary (SPAPM) (29 cases), complex papillary (28 cases) and highly complex papillary (six cases). For statistical analysis, the last two groups were merged together (CPAPM). The results showed that increased histological complexity was associated with significant increase of proliferative capacity and alterations of the cell cycle control. The median Ki-67 index was 1.5% in SPAPM and 4.8% in the CPAPM. Also, alterations of the cell cycle regulators were significantly higher in the CPAPM than in the SPAPM. NAPM was generally similar to normal breast epithelium. Apocrine cells were negative for p16 while pRb was expressed in all cases. These findings suggest that in complex forms of APM, there is a considerable degree of cellular unrest. This may contribute to increased susceptibility to carcinogenesis.

Aims: To evaluate the frequency of neuroendocrine cell hyperplasia (NEH) in resected neuroendocrine tumours and non-neuroendocrine cell carcinomas and to study its relationship to selected clinical parameters., Methods and Results: Random blocks without tumour from resected typical carcinoids (TCs, n = 46), atypical carcinoids (ACs, n = 14), large cell neuroendocrine carcinomas (LCNECs, n = 18), small cell carcinomas (SCLCs, n = 22), adenocarcinomas (ADENOs, n = 26) and squamous cell carcinomas (SCCs, n = 18) were stained for CD56 and evaluated for linear proliferations, cell aggregates (>4 CD56+ cells), and tumourlets (<5 mm with basement membrane invasion). There was a statistically significant difference between the frequency of NEH in all neuroendocrine tumours (TC/AC/LCNEC/SCLC, 35/100, 35%) (P = 0.009) when compared with non-neuroendocrine carcinomas (ADENO/SCC, 6/44, 14%) and in the frequency of NEH in TC (21/46, 46%) versus all other tumours (AC/LCNEC/SCLC/SCC/ADENO, 20/98, 20%) (P = 0.001). There was increased frequency of NEH in peripheral TCs (8/13, 62%) compared with central TCs (14/33, 43%) (P = 0.33). There was no association between smoking history and NEH. Clinical and imaging data showed no evidence of an increased frequency of obliterative bronchiolitis in patients with NEH., Conclusions: NEH is significantly increased in the background lung of neuroendocrine tumours when compared with non-neuroendocrine carcinomas, supportive data for NEH having neoplastic potential.

Aims: Apocrine adenosis (AA) is generally considered a benign disease of the breast. However, recent studies have suggested a precancerous potential for some of these lesions. The aim was to investigate the status of cell cycle proteins previously reported to be deregulated in breast cancer to identify their possible role in AA., Methods and Results: The cases were categorized into AA without atypia (NAA) and atypical AA (AAA). Using immunohistochemistry, the expression of cyclin D1, cyclin A, p27, p21, p16, pRb and Ki67 was determined in 29 NAA and 16 AAA cases. Cyclin D1, p21 and cyclin A were overexpressed in 58.6%, 51.7% and 31.8% of the NAA cases, respectively, whereas 81.3%, 62.5% and 41.7% of the AAA cases showed overexpression of cyclin D1, p21 and cyclin A, respectively. All cases were negative for p16, whereas pRb was expressed in all cases. Furthermore, proliferation in AA (4.5%) was significantly higher than that of normal breast epithelium (1%). There was no statistical significance in the degree of proliferation between the NAA (3.7%) and AAA (4.8%) groups., Conclusions: The study indicates that NAA and AAA are biologically similar. A subset of AA defined by increased proliferation and significant cell cycle alterations may be susceptible to oncogenesis.

Introduction: This study aimed at determination of circulating soluble interleukin-2 receptor (IL-2 R) alpha in the sera of patients with systemic lupus erythematosus (SLE) and correlating the level of expression of these receptors with the SLE disease activity., Materials and Methods: The study included 55 patients with SLE and 20 healthy volunteers as controls. The following investigations were done: serum complement component 3, complement 4, erythrocyte sedimentation rate, complete blood count, serum creatinine, creatinine clearance, 24-hour urinary protein, urinalysis, and serum soluble IL-2R alpha level. Kidney biopsy was performed and examined with light microscopy for patients with lupus nephritis by a single pathologist blinded to the clinical activity of the disease. The results were analysed in relation to the clinical activity index of systemic lupus activity measure (SLAM)., Results: The study showed that levels of soluble IL-2R alpha were significantly higher in the total group of patients with SLE compared to the controls (P < .001). Furthermore, serum IL-2R alpha levels were significantly higher in patients with lupus nephritis than those without nephritis. There were strong positive correlations between IL-2R alpha levels and the SLAM score, histological activity index, erythrocyte sedimentation rate, and 24-hour urinary protein excretion. Also, significant inverse correlations with complement 3 and packed cell volume was observed (r = 0.738; r = 0.669; r = 0.328; r = 0.705; r = -0.444; r = -0.420, respectively)., Conclusions: Serum soluble IL-2R alpha is a reliable marker of disease activity in patients with SLE and could be used as an indicator of early renal involvement with the possibility of using it for follow-up.

Overexpression and/or amplification of c-myc oncogene are known to occur in human breast carcinomas, particularly those of high grade. Apocrine metaplasia (APM) is a common finding within fibrocystic change, and in some cases appears to be associated with an elevated risk of subsequent breast cancer. It has been suggested that apocrine metaplasia within sclerosing adenosis of the breast, also called apocrine adenosis (AA), has a premalignant potential. Little, however, is known about cellular level genetic alterations in either APM or AA of the breast. Because of this, c-myc expression and amplification in APM and AA were studied. Fluorescence in situ hybridisation (FISH) is a methodological approach to detecting these genetic alterations. In this study, APM and AA were studied immunohistochemically to detect c-myc oncoprotein expression, and FISH was employed using a DNA probe for the c-myc gene in archival tissue sections of cases of APM and AA of the breast. Nuclear immunostaining for c-myc was seen in all APM and AA cases studied, but amplification of the c-myc gene was not seen in any cases with APM or AA. The results of this study indicate that c-myc overexpression appears to occur early in breast oncogenesis. Amplification of the c-myc gene does not occur in APM or AA of the breast, however, suggesting that this particular genetic alteration constitutes a late event in the pathogenesis of breast carcinomas.

Molecular evidence has recently suggested a number of different pathways leading to the development of ductal carcinoma of the breast. The links between atypical ductal hyperplasia and low-grade ductal carcinoma in situ and lobular neoplasia and lobular carcinoma are well known pathologically, but high-grade in situ and invasive carcinomas appear to have a different biological oncogenetic pathway. Morphologically there is a similarity between apocrine cells and some cases of high-grade ductal carcinoma. In order to investigate this possibility a number of different biological markers known to occur in high-grade breast carcinomas were assessed in both apocrine metaplasia (APM) and a putative premalignant lesion called apocrine change within sclerosing adenosis (AA). In 64 cases of APM and 18 cases of AA we examined for expression of c-erbB2, p53, Bcl-2, Bax, c-myc and Ki-67 proteins using immunocytochemistry. c-erbB2 expression was seen in 55.6% of AA cases and in 10.9% of APM cases. p53 expression was detected in 27.8% of AA cases but only 1.6% of APM cases. All cases of AA and APM were negative for the anti-apoptotic protein Bcl-2, but all the APM and 33.3% of AA cases showed cytoplasmic positivity for Bax, a pro-apoptotic protein. All the cases of AA and APM were positive for c-myc oncoprotein, however, the mean percentage of nuclear positivity was 50% in AA and 37% in cases of APM cases. The mean percentage positivity for Ki-67, a proliferation associated antigen, was 3.6% in AA and 1.3% in APM. The results indicate that a subset of breast lesions containing APM epithelium show abnormal oncoprotein and apoptosis-related protein expression and have a higher proliferation rate.

Loss of heterozygosity (LOH) and allelic imbalance (AI) at loci reported to show allele loss and/or imbalance in preinvasive and invasive breast cancer were examined in 41 cases of apocrine metaplasia (APM) of the breast using a microdissection technique, polymorphic microsatellite markers, and the polymerase chain reaction (PCR). Occasional examples of LOH and/or AI were identified in 2/28 (7.1%) informative cases at 1p (MYCL1), 2/14 (14.3%) at 11q (INT2), 1/15 (6.7%) at 13q (D13S267), 3/22 (13.6%) at 16q (D16S539), 2/23 (8.7%) at 17p (TP53), and 1/11 (9.1%) at 17p (D17S513) and 3/16 (18.8%) at 17q (D17S250). The finding of LOH/AI in cases of APM indicates that a subset of APM appears clonal, but the significance of allelic loss or imbalance in the pathogenesis of APM or its possible subsequent progression to carcinoma is not yet clear and requires further investigation. Clinical follow-up of these particular cases of APM showing LOH/AI would be of further value., (Copyright 2002 John Wiley & Sons, Ltd.)

Aims: Ductal carcinoma in situ (DCIS) of the breast has been diagnosed increasingly since the advent of mammographic screening. In contrast to the situation in invasive breast carcinoma, there are no reports on androgen receptor (AR) status in DCIS and few reports on oestrogen (ER) and progesterone (PR) receptors., Methods: AR expression was examined in 57 cases of DCIS of the breast and correlated to the degree of differentiation and ER/PR status using immunohistochemical methods., Results: AR positivity was noted in 19 of the cases, whereas the other 38 cases were negative. There was no significant association between AR expression and the degree of differentiation of DCIS; three of the 13 well differentiated DCIS cases, 10 of the 19 intermediately differentiated cases, and six of the 25 poorly differentiated cases were positive (p = 0.093). However, a strong association was shown between the expression of ER (p < 0.0001) and PR (p = 0.002) and the degree of differentiation of DCIS. In addition, no significant association was found between the expression of AR and the expression of ER (p = 0.26) or PR (p = 0.57) in DCIS of the breast., Conclusions: A large number of cases of DCIS of the breast express AR and this may be associated with apocrine differentiation, which may impact on accurate typing of DCIS. Moreover, the expression of AR (but not ER or PR) in DCIS does not appear to be associated with the degree of differentiation.

Relapsing polychondritis (RP) is a rare inflammatory multiorgan disorder affecting cartilaginous structures and other connective tissues. Serious cardiovascular complications have been reported in patients with RP, the most frequent being aortic or mitral regurgitation and aortic aneurysms. Aortitis is a very rare complication. An unusual case of active aortitis in a patient with RP, despite intensive immunosuppressive treatment, is described with a special emphasis on the pathological findings.

Recently, there have been studies suggesting that apocrine adenosis of the breast is a putative precancerous lesion, despite the generally held view that apocrine adenosis is benign. Because apocrine adenosis is almost always present as a small area or areas, it cannot be easily studied by conventional methods. In this study, areas of apocrine adenosis were microdissected from archival paraffin-embedded tissue to examine loss of heterozygosity and allelic imbalance compared with normal breast tissue epithelium from the same patients. Seventeen cases of apocrine adenosis, four associated with carcinoma, were analyzed using polymorphic microsatellite markers and polymerase chain reaction for loss of heterozygosity/allelic imbalance at eight loci that were reported to show allele loss or imbalance in invasive and in situ breast cancer. Loss of heterozygosity/allelic imbalance was detected in six of 17 cases of apocrine adenosis; three of 12 (25%) informative cases at 1p (MYCL1), two of seven (28.6%) at 11q (INT2), one of three (33.3%) at 13q (D13S267), two of 12 (16.7%) at 16q (D16S539), and two of 10 (20%) at 17q (D17S250). Neither loss of heterozygosity nor allelic imbalance has been identified at 1p (D1S252), 17p (TP53), or 17p (D17S513). In two of the four cases associated with carcinoma, loss of heterozygosity/allelic imbalance was seen in the same allele as in the synchronous carcinoma. These results suggest that molecular alterations, such as loss of heterozygosity and allelic imbalance, identified in apocrine adenosis may constitute an early event in the pathogenesis of breast cancer; reinforcing the possibility of apocrine adenosis being a putative precancerous lesion.

Amplification of the c-erbB2 oncogene and numerical aberrations of chromosome 17 occur in human breast carcinomas. Apocrine adenosis (AA) of the breast has been shown occasionally to have c-erbB2 overexpression and a possible premalignant potential, but little is known about cellular level genetic alterations in AA of the breast. Fluorescence in situ hybridization (FISH) is a new approach to detect these. In this study, a series of AA was studied by immunohistochemistry for c-erbB2 protein expression and by FISH using dual colour DNA probes for the c-erbB2 gene and the centromeric region of chromosome 17. Cell membrane immunostaining was seen in 10/18 (55.6%) AA cases, but unequivocal c-erbB2 gene amplification or chromosome 17 aneusomy was not seen. The results of this study suggest that c-erbB2 overexpression without amplification may occur early in breast oncogenesis. Amplification and numerical chromosome aberrations may occur later in the pathogenesis of apocrine-derived breast carcinomas., (Copyright 2000 John Wiley & Sons, Ltd.)

Aim: To investigate the receptor status of the sex steroid hormones in apocrine metaplasia of the breast., Methods: 82 cases of apocrine metaplasia, including 18 of the rare lesion apocrine adenosis, were studied immunohistochemically for the expression of androgen receptor, oestrogen receptor, and progesterone receptor proteins on formalin fixed, paraffin embedded tissue sections. The standard avidin biotin complex (ABC) technique was followed and appropriate positive and negative controls were used., Results: All the studied cases (82/82) were positive for androgen receptor, but were negative for oestrogen receptor and progesterone receptor., Conclusions: Apocrine metaplastic epithelium, unlike the normal breast epithelium, is responsive to androgens, through androgen receptors, rather than to the female sex hormones. This may have clinical implications.

A total of fifteen clinically and parasitologically proven adult cases of cutaneous leishmaniasis were studied for the demonstration of premalignant factor(s). The levels of antibodies against Leishmania parasite were measured with the indirect haemagglutination test (IHAT) and evaluated with the results of lymphoblast transformation test (LTT), a tumour suppressor gene (P53) and an asportic proteinase enzyme (Cathepsin D). Three patients (females) refused to be biopsied. The results showed a direct correlation between elevation of IHAT in 7/12 patients (Titers 1/128 to 1/512) and elevation of LTT in 7/12 patients (82 to 90%). On the other hand, two males with low (?) seropositive IHAT (1/64) and low LTT (20 & 40%) gave positive P53 antibody and moderate (1) and marked (1) degrees Cathepsin D. So, it is concluded that cutaneous leishmaniasis infection particularly chronic one favours the premalignant changes in the granulomatous lesions.

To assess the role of levamisole in treatment of different types of warts, a double-blind study was conducted on 40 patients with different types of warts. Patients were divided into two equal groups, A and B. Group A received levamisole 5 mg/kg body weight on 3 consecutive days every 2 weeks for a period up to 5 months, while patients of group B received placebo for the same period. In group A, 12 patients showed complete cure (60%), two showed partial cure (10%), and the remaining six patients showed no response (30%). In group B, complete cure was achieved only in one case. The higher cure rate was observed in plane and common warts, while plantar warts showed no improvement with levamisole treatment.