bluuebunny/crossref_metadata_2025 huggingface dataset:
p57kip2 is useful in the classification and differential diagnosis of complete and partial hydatidiform moles
Authors: Jun S‐Y , Ro J Y , Kim K‐R
Published: December 2004

Aims:  To determine the utility of p57kip2 in the diagnosis of hydatidiform mole. p57kip2 protein is a cyclin‐dependent kinase inhibitor (CDKI) and is strongly paternally imprinted, being expressed from the maternal allele. It has been hypothesized that complete mole (CHM) with only the paternal genome would display reduced or nearly absent expression of p57kip2 compared to partial mole (PHM) having both paternal and maternal genomes.

Methods and results:  The immunohistochemical expression of p57kip2 protein was investigated using paraffin‐embedded tissue sections in histologically unequivocal cases of CHM (n = 51), PHM (n = 7), invasive mole (n = 1), and hydropic miscarriage (n = 2), as well as in histologically undetermined cases (n = 9). In the histologically unequivocal complete and invasive moles, expression of p57kip2 was absent except for one case in which villous cytotrophoblast covering the villous stroma was positive (51/52) as well as villous stromal cells (51/52). In contrast, it was strongly and continuously expressed in both villous cytotrophoblast and stromal cells in all cases of PHM and hydropic miscarriage. Among the nine histologically undetermined cases, five cases showing p57kip2 immunopositivity and hyperploid DNA were classified as PHMs, two cases showing p57kip2 immunonegativity and hyperploidy as CHMs, and two cases with p57kip2 immunopositivity and diploid DNA as hydropic miscarriage and diploid PHM, respectively, upon review of the histopathological findings. Intermediate trophoblast forming trophoblastic columns or anchoring villi and extravillous trophoblast at the implantation site showed variable expression of p57kip2 in all gestational conditions. Maternal decidua showed diffuse and strong p57kip2 expression, whereas syncytiotrophoblast was completely negative in all cases regardless of the diagnosis.

Conclusions:  In summary, p57kip2 immunostaining results correlated well with morphological features of molar pregnancies and were helpful in determining histologically equivocal cases.
Immunoreactivity of cytokeratins (CK7, CK20) and mucin peptide core antigens (MUC1, MUC2, MUC5AC) in adenocarcinomas, normal and metaplastic tissues of the distal oesophagus, oesophago–gastric junction and proximal stomach
Authors: Flucke U , Steinborn E , Dries V , Mönig S P , Schneider P M , Thiele J , Hölscher A H , Dienes H P , Baldus S E
Published: December 2004

Aims:  Adenocarcinomas of the distal oesophagus and especially the oesophago–gastric junction have shown an increasing incidence during the last decade. Definition of subgroups according to different sites of development, histogenesis or aetiology may prove to be valuable for clinical diagnosis and treatment. Previous studies have shown differences in cytokeratin patterns between Barrett's metaplasia of the oesophagus and intestinal metaplasia in the stomach. The aim of our study was to investigate whether the expression of certain cytokeratins (CK7, CK20) and mucins (MUC1, MUC2, MUC5AC) exhibit clear‐cut patterns, thus allowing a subclassification of adenocarcinomas of the oesophago–gastric junction. The possibility of a relationship between antigen expression and the presence or absence of Barrett's metaplastic epithelium was also studied.

Methods and results:  CK7, CK20, MUC1, MUC2 and MUC5AC were visualized in six adenocarcinomas of the distal oesophagus, 29 adenocarcinomas of the oesophago–gastric junction and eight adenocarcinomas of the proximal stomach. CK7, CK20 and MUC1 were strongly expressed in the great majority of all neoplasms under study, whereas MUC2 and MUC5AC were absent or only faintly detectable. CK20 exhibited a significantly stronger expression in poorly differentiated tumours (G3) and MUC1 immunoreactivity correlated with tubular and papillary versus signet‐ring cell histopathology. Other statistically significant correlations between antigens and histopathological features (pTNM stage, grading, histopathological subtype, presence/absence of Barrett's epithelium) were not observed.

Conclusions:  According to our results, most adenocarcinomas of the oesophago–gastric junction show a CK7+, CK20+, MUC1+ phenotype irrespective of the presence or absence of Barrett's epithelium. The immunohistochemical data suggest a similar histogenesis of these tumours.
Radial intratumoral increase and correlation of microvessels and proliferation in solid breast carcinoma
Authors: Begum R , Douglas‐Jones A G , Morgan J M
Published: December 2004

Aims:  To compare correlations between different morphometrically assessed measurements of tumour microvasculature and to identify those which show closest correlation with Ki67 and to examine radial intratumoral distribution of microvessels and proliferation.

Methods and results:  Immunohistochemically defined microvessels and Ki67+ cells were quantified in sequential fields of 0.12 mm2 (×600) in four transects in each of five tumours. The total number of vessels (TNV) correlated more closely with proliferative activity than the numbers of vessels with a discernible lumen (TLV) and TNV decreased towards the centre of the tumour whereas TLV did not. A higher proliferative index (PI) was found at the periphery of the tumours. Comparison between transects through subjectively identified microvessel hot‐spots and non‐hot‐spot transects showed similar mean, median and peak vessel counts but showed a different distribution on χ2 analysis.

Conclusions:  TNV correlates most closely with PI in breast carcinomas. There is marked variation in microvessel density and PI between fields of 0.12 mm2 but there is a significant radial reduction in both from the edge towards the centre of tumours.
Genetic imbalances with impact on survival in colorectal cancer patients
Authors: Knösel T , Schlüns K , Stein U , Schwabe H , Schlag P M , Dietel M , Petersen I
Published: December 2004

Aims: To investigate the prognostic significance of chromosomal alterations in colorectal cancer patients. Histopathological tumour classification is still considered to be the gold standard for the characterization of solid tumours. However, it is well known that such established parameters do not satisfactorily predict the clinical outcome in individual cases. Markers that reliably predict survival are needed. These markers should guide the clinical treatment of neoplastic disease.

Methods and results: Chromosomal imbalances in 61 colorectal carcinoma specimens in 37 patients determined by comparative genomic hybridization were correlated with patient survival using custom‐made computer software which enabled the assessment of individual chromosomal loci. Kaplan–Meier analysis revealed that over‐representations of 2p14‐15, 6q23‐6q24, 15q22‐15q23, 22q11.2 and deletions of 1p36.1‐36.2, 4q31.3, 4q35, 8q12‐q21, 8p11.2 and 9p22 were significantly associated with shorter disease‐specific survival, whereas over‐expression of 20q13.3 and deletion of 18q11.2 were significantly associated with longer disease‐specific survival in this collection of colorectal cancers. Multivariate Cox proportional hazards regression models consistently identified gains of 2p14‐15, 15q22‐23, 22q11.2 and losses of 1p36.1‐36.2 and 4q35 as independent markers of shorter patient survival carrying greater significance than the classical clinicopathological parameters of nodal status and tumour grade.

Conclusions: These five markers allow a molecular categorization of patients into high and low clinical risk groups. Thus, the genomic data have refined the histopathological classification highlighting the necessity for a supplementary genetically based stratification of colorectal cancer.
Transplant histopathology for the general histopathologist
Authors: Wallace W A H , Bellamy C O C , Rassl D M , Harrison D J
Published: December 2004

The number of patients undergoing solid organ transplants and surviving long‐term has increased enormously in the last 10 years. This means that pathologists in non‐specialist transplant centres are increasingly involved in the interpretation of biopsy and autopsy material from allograft recipients. This includes evaluation of allograft histology, or specimens from other native tissues, which nonetheless still have to be assessed in the setting of transplantation and immunosuppressive therapy. In this first review article we will provide an overview of the pathology of lung transplantation, and briefly describe heart and pancreatic transplants, as well as aspects of general surgical pathology and the role of the autopsy in these patients.
Cytokeratin‐positive interstitial cell neoplasm: a case report and classification issues
Authors: Schuerfeld K , Lazzi S , De Santi M M , Gozzetti A , Leoncini L , Pileri S A
Published: December 2004

Aims:  Tumours of dendritic/accessory cell origin are rare neoplasms arising in lymph nodes. Among these, tumours derived from cytokeratin‐positive interstitial reticulum cells (CIRCs), a subset of fibroblastic reticulum cells, are reported even less frequently. The International Lymphoma Study Group (ILSG) has recently proposed a classification for tumours of histiocytes and accessory dendritic cells in which CIRC tumours are not included. We report a case of a CIRC tumour arising in a submandibular lymph node of a 66‐year‐old male.

Methods and results:  The neoplasm was composed of spindle cells with elongated or round nuclei, prominent nucleoli and abundant cytoplasm. These cells were arranged in a diffuse fascicular and vaguely whorled pattern. The tumour cells stained diffusely for S100, vimentin, desmin, lysozyme, and focally for CD68 and cytokeratins 7, 8, 18, CK‐AE1 and CK‐pool. Electron microscopy was performed for further evaluation on samples taken from the paraffin block; this revealed cytoplasmic projections and rudimentary cell junctions.

Conclusions:  Histopathologist should be aware of the existence of tumours deriving from CIRCs, as these cases may be misdiagnosed as metastatic carcinoma. Careful clinical and pathological evaluation is necessary to exclude this possibility.
Seminal immunoreactive relaxin in domestic animals and its relationship to sperm motility as a possible index for predicting the fertilizing ability of sires
Authors: Kohsaka T. , Hamano K. , Sasada H. , Watanabe S. , Ogine T. , Suzuki E. , Nishida S. , Takahara H. , Sato E.
Published: December 2004

Although immunoassayable relaxin has been detected in human and boar seminal plasma, there is no evidence suggesting the existence of immunoreactive relaxin in the seminal plasma of other domestic animals. The first objective of this study was to determine whether immunoreactive relaxin was present in the seminal plasma of bulls, rams and he‐goats. In addition, the correlation of immunoreactive relaxin with sperm motility as an index for predicting the fertilizing ability of bull sires was investigated. Semen with normal sperm motility was collected from bulls, rams and he‐goats, and the relaxin immunoreactivity of the semen samples was measured using a time‐resolved fluoroimmunoassay (TR‐FIA) for porcine relaxin that we developed. The presence of relaxin immunoreactivity was demonstrated in seminal plasma from bulls, rams and he‐goats. The level of immunoreactive relaxin in seminal plasma was the highest in bulls followed by humans, rams, boars and he‐goats in that order, when relaxin levels in boar and human semen having normal sperm motility were also assayed under the same conditions. When the correlation between the seminal plasma level of immunoreactive relaxin and sperm motility was examined in bull semen samples as an index for predicting fertilizing ability, it was found that the relaxin level was significantly correlated with the percentage of spermatozoa showing the most intensive motility (r = 0.64, p < 0.05). These results indicate that immunoreactive relaxin is widely found in the seminal plasma of domestic animals and that measuring the relaxin concentration of seminal plasma may be useful to identify subfertile sires or predict the fertility potential of individual sires.
A quick, practical test procedure to evaluate the performance of instruments used for in vitro UV protection measurements
Authors: Klette E. , Wendel V. , Wittern K. P. , Gers‐Barlag H.
Published: December 2004

Synopsis

The in vitro determination of the UV protection of sunscreens is usually performed by means of transmission measurements with special photometers. Many different instruments are used. Besides numerous commercially available instruments, which are equipped by the manufacturer for the specific measurement, other modular instruments are used. We present here a quick and practical method to evaluate the performance of these instruments with respect to their measuring ranges and to compare the uniformity and reliability of the results obtained with these instruments.
A randomized placebo‐controlled trial of adefovir dipivoxil in advanced HIV infection: the ADHOC trial
Authors:   ADHOC International Steering Committee
Published: December 2004

Objectives

To assess the efficacy and safety of adefovir dipivoxil (ADV) added to stable background antiretroviral therapy (ART) in HIV‐infected individuals with advanced HIV disease.

Methods

ADHOC was a randomized, double‐blind, placebo‐controlled, international multicentre trial. Three hundred and one individuals with CD4 cell counts < 100 cells/μL or < 200 cells/μL with nadir < 50 cells/μL were allocated to receive either 120 mg ADV (subsequently 60 mg) (n = 161) or matching placebo (n = 140) once daily.

Results

Over a median follow‐up of 76 weeks, 23 (14%) and 18 (13%) participants assigned ADV and placebo, respectively, developed a new AIDS event or died (hazard ratio = 1.23, 95% confidence interval 0.66–2.29,P= 0.51). There was a lower incidence of new or recurrent herpes events in the ADV group (P = 0.009). The mean increase in CD4 cell count from baseline to week 24 was 23.0 and 24.4 cells/µL in ADV and placebo groups, respectively (P = 0.89), and the mean decrease in RNA was 0.32 and 0.35 log10copies/mL at week 24 (P = 0.87) in a subset of participants. There was greater weight loss in the ADV group during the trial (P = 0.007). One hundred and twenty‐four participants (41%) had stable background ART in the 8 weeks prior to and the 24 weeks after randomization. There was no significant imbalance in background ART regimens between the two treatment groups. Ninety‐seven serious adverse events (SAEs) occurred, 65 and 32 in the ADV and placebo groups, respectively, with significantly shorter time to first SAE in the ADV group (P = 0.002). A total of 33 participants developed proximal renal tubular dysfunction during the trial, all but one in the ADV group.

Conclusions

Due to the early termination of recruitment, ADHOC was unable to assess the original objective of clinical disease progression. Adding ADV to background antiretroviral therapy in advanced HIV disease did not provide immunological or virological improvement compared with placebo. Furthermore, at the doses used in this trial, ADV was associated with a significantly higher incidence of SAEs.
Estimating the effect of antiretroviral treatment during HIV seroconversion: impact of confounding in observational data
Authors:   CASCADE Collaboration
Published: December 2004

Objective

To assess whether treatment with antiretroviral drugs within the first 3 months of infection with HIV affects medium‐term health outcomes.

Design and methods

Data from 20 cohorts in Europe and Australia were used Concerted Action on SeroConversion to AIDS and Death in Europe (CASCADE). Analysis was restricted to persons seroconverting in 1988–1998 who started antiretroviral treatment in the first 3 months or 1–2 years from seroconversion. The relationship between times to low CD4 count, AIDS and death and time of initiation of treatment was estimated using proportional hazards models.

Results

Seroconversion illness was more common in those who began antiretroviral treatment in the first 3 months (73%) than in those who started treatment within 1–2 years post‐seroconversion (33%). Subjects receiving early antiretroviral treatment had times to AIDS and to CD4 counts <200 cells/μL that were intermediate between those of subjects starting treatment within 1–2 years and those of the subset of these subjects starting treatment within 1–2 years who also had a prior CD4 count of >350 cells/μL and no prior AIDS diagnosis.

Conclusions

On the basis of these analyses, the effect of antiretroviral treatment initiation during HIV seroconversion is uncertain. It may result in lower rates of progression compared with starting antiretroviral treatment at 1–2 years, but the early antiretroviral treatment group had a similar or even higher incidence of low CD4 counts and AIDS events than the group who started antiretroviral treatment within 1–2 years with CD4 counts over 350 cells/μL and no prior AIDS diagnosis. Estimates of the effect of early treatment are probably confounded with a number of factors, including, in particular, reasons for treatment initiation.
Milking and milk processing: traditional technologies in the yak farming system of the Qinghai‐Tibetan Plateau, China
Authors: Dong S K , Long R J , Kang M Y
Published: December 2004

Yak milk and its products are widely consumed by local herders and are regarded as the resources of economic income by the households on the Qinghai‐Tibetan Plateau. Yak raisers have developed their own milking skills and milk‐processing technologies through a long history of yak keeping. All of these traditional skills and technologies have their own characteristics. In this paper, the methods and procedures of milking and milk processing in yak farming systems are reviewed.
Are salinas a suitable alternative breeding habitat for Little Terns Sterna albifrons?
Authors: Catry Teresa , Ramos Jaime A. , Catry Inês , Allen‐Revez Manuel , Grade Nuno
Published: December 2004

This paper describes the breeding population, breeding habitats and reproductive variables of Little Terns Sterna albifrons in natural (sandy beaches) and alternative (salinas) habitats. Studies of nesting success conducted between 1998 and 2002 in these two types of habitat were combined with a literature review of census work from the past 30 years in order to assess whether salinas are suitable alternative breeding habitat for Little Terns. Most of the Portuguese Little Tern population now breeds in salinas. Census data from the last 30 years show that this is a recent breeding behaviour, because until the 1990s most colonies were located on sandy beaches. Destruction and disturbance of the natural habitat has caused this habitat shift. Despite this shift, the Portuguese Little Tern breeding population did not decline during this period and no significant differences were found in nesting success between natural and alternative habitats. This might indicate that salinas are a suitable alternative breeding habitat for Little Terns, but differences in laying period, clutch size and egg size were recorded between birds nesting on sandy beaches and in salinas in the same area. Birds nested earlier on sandy beaches and laid larger clutches and eggs than in salinas. These data suggest that, when both habitats are available, older and/or higher quality birds prefer sandy beaches for breeding, presumably trying to re‐nest in salinas when first breeding attempts failed. We discuss conservation priorities and management actions for both habitats.
Why Seychelles Warblers fail to recolonize nearby islands: unwilling or unable to fly there?
Authors: Komdeur Jan , Piersma Theunis , Kraaijeveld Ken , Kraaijeveld‐Smit Femmie , Richardson David S.
Published: December 2004

The Seychelles WarblerAcrocephalus sechellensisis a rare island endemic which, from 1920 to 1988, occurred only on Cousin Island (29 ha) in the Seychelles. Despite the saturated nature of this population and the possibility of obtaining higher reproductive success on new nearby islands, inter‐island dispersal by Seychelles Warblers is extremely rare (0.10%). We test the hypothesis that Seychelles Warblers show an adaptation typical for island birds: a low‐cost reduced‐size flight apparatus. We compared the anatomy of the flight apparatus (wing shape, wing loading, skeletal parts and musculature) of Seychelles Warblers with that of three closely related migratoryAcrocephalusspecies (Eurasian Reed WarblerA. scirpaceus, Australian Reed WarblerA. australisand African Reed WarblerA. baeticatus). Seychelles Warblers do not differ from the migratory warblers in pectoral mass and skeletal attachment area relative to body mass, wing shape and wing loading. Seychelles Warblers show the morphological structures required for sustained flight, but may have the behavioural reluctance to cross what they may regard as extensive bodies of water.
How Do Patients Choose Physicians? Evidence from a National Survey of Enrollees in Employment‐Related Health Plans
Authors: Harris Katherine M.
Published: December 2004

Objective. This study examines the process by which patients search for and choose physicians.

Data Source. A survey to a random sample of individuals between the ages of 21 and 64 with employer‐related health benefits, drawn from a nationally representative panel of households.

Study Design. Logit models are used to measure the effect of patient characteristics on the probability of (1) using alternative sources of information to support the choice of a current physician, (2) seriously considering another physician before choosing a current physician, and (3) stating a willingness to switch physicians when information suggests that other health plan doctors receive higher quality ratings.

Principal Findings. Although a minority of respondents actively searches for a physician, there appears to be substantial variation in the degree of consumer activism across patient subgroups. Poor health status, higher levels of service use in the past year, and stronger ties to individual physicians are associated with less consumer activism. At the same time, greater levels of consumer activism were found among racial and ethnic minorities, among those who report using information to choose their physicians, and among those who switched physicians as a result of dissatisfaction some time in the past five years. Source of quality information (medical experts versus patient advocates) did not influence stated willingness to switch physicians.

Conclusions. Despite predictions of the increasing importance of consumer choice in shaping the health care delivery system, the results largely confirm the image depicted in the previous literature of patients as passive health care consumers of physician services, and highlight the importance of investments in the development of decision support tools in consumer‐driven health care systems.
The spectrum of primary cutaneous elastolytic granulomas and their distinction from granuloma annulare: a clinicopathological analysis
Authors: Limas C
Published: December 2004

Aims:  Actinic granuloma (AG) and annular elastolytic giant cell granuloma (AEGCG) are terms commonly applied to cutaneous lesions characterized by elastolysis, elastophagocytosis and a multinucleated cell infiltrate. The aim of this study was to clarify the relationship of these lesions to granuloma annulare (GA) which they resemble clinically.

Methods and results:  The clinicopathological data of 20 patients whose biopsies showed the histology of elastolytic granuloma as well as those of previously published cases with identical tissue changes were analysed to assess differences between AG, AEGCG and GA. The tissue changes of AG and AEGCG are identical and differ substantially from GA because of the predominant elastolysis and elastophagocytosis in the absence of necrobiosis and palisading granuloma. Actinic and/or thermal injury could be elicited frequently in the patient's history, but not always.

Conclusions:  AG may be considered as an aetiopathological subdivision of AEGCG. Patients with biopsies showing both GA and AEGCG are occasionally encountered. AEGCG is easily differentiated from incidental elastolysis which may be seen in a variety of aetiologically unrelated processes.
T cell activation: in vivo veritas
Authors: Fazekas De St. Groth Barbara , Smith Adrian L , Higgins Caroline A
Published: December 2004

Phenotypic changes in CD4+ T cells undergoing antigen‐dependent activation were compared in vivo and in vitro. The most obvious difference was in expression of CD25, the alpha chain of the high affinity receptor for IL‐2. High level expression of CD25 in vivo is restricted to a small fraction of the cells at the leading edge of the cell division profile, whereas all activated cells express high levels of CD25 in cultures responding to antigen. Because IL‐2 is known to upregulate expression of CD25 in preactivated T cells, this suggests a difference in IL‐2 exposure in the two responses. A number of other markers, including CD54, show a similar difference in the pattern of expression in vivo and in vitro. Using 6‐colour flow cytometry, it was demonstrated that the small percentage of cells expressing CD25 in vivo coexpresses a very high level of a number of other activation markers, including CD38, CD44 and Ly‐6A/E, suggesting that these may also be upregulated by autocrine IL‐2.
Deep penetrating naevus: clinicopathological study of 31 cases with further delineation of histological features allowing distinction from other pigmented benign melanocytic lesions and melanoma
Authors: Robson A , Morley‐Quante M , Hempel H , McKee P H , Calonje E
Published: December 2004

Aims:  To examine a series of deep penetrating naevus (DPN) and discuss the differential diagnosis of pigmented, deep penetrating melanocytic lesions and their biological potential. DPN has been described as a variant of common acquired intradermal melanocytic naevus. DPN remains poorly recognized by pathologists, partly attributable to its relatively rare occurrence.

Methods and results:  Thirty‐one cases of deeply pigmented lesions were studied. The patients included 17 females and 14 males with an age range between 3 and 56 years (mean 25.8, median 23). The common clinical sites were face (n = 10) back (n = 6) and lower extremity (n = 7). The clinical diagnoses included various benign melanocytic naevi, and malignant melanoma, as well as non‐melanocytic lesions. Histologically, all cases presented as wedge‐shaped lesions composed of fusiform cells but also epithelioid melanocytes, with pale cytoplasm and oval nuclei. Pigment was identified in melanophages but also within lesional melanocytic cells. Nine cases contained mitotic figures. Nine cases showed the coexistence of ‘ordinary’ common acquired naevocytes, and seven lesions showed overlapping features with either ordinary blue naevus or Spitz naevus. In 13 lesions there was at least one feature that may cause concern as to the biological nature of the tumour. These include asymmetry, cytological atypia, inflammation, or an ‘expansile’ advancing margin. Each tumour was treated by simple excision; one lesion recurred after 1 year. No tumour metastasized.

Conclusions:  DPN is a distinct variant of melanocytic naevus. In some cases the histological features overlap with other benign melanocytic lesions. Criteria for recognizing malignant examples remain unclear, but cytological atypia and low mitotic activity do not necessarily portend a sinister outcome.
Applications of microarrays to histopathology
Authors: Van De Rijn M , Gilks C B
Published: December 2004

High‐throughput microarray technologies have the potential to impact significantly on the practice of histopathology over the coming years. Global gene expression profiling allows for a systematic search of all human genes for novel diagnostic and prognostic markers and for potential therapeutic targets. Likewise, gene copy number changes can be determined on a gene‐by‐gene basis using microarrays. Tissue microarrays are an efficient method to extend and validate the findings obtained from the initial ‘discovery’ phase of the research, done using cDNA microarrays. In addition, tissue microarrays can be used for quality assurance for immunohistochemical and in situ hybridization procedures. In this review we give a brief overview of microarray technology and research uses, and discuss potential applications of microarrays in the practice of diagnostic histopathology.
WT‐1 assists in distinguishing ovarian from uterine serous carcinoma and in distinguishing between serous and endometrioid ovarian carcinoma
Authors: Al‐Hussaini M , Stockman A , Foster H , McCluggage W G
Published: December 2004

Aims : It has been suggested that WT‐1 is helpful in distinguishing a primary ovarian serous carcinoma (OSC) from a primary uterine serous carcinoma (USC). Since both neoplasms are often disseminated at diagnosis and since USC often spreads to the ovary and vice versa, it may be difficult to ascertain the primary site. This is important, since adjuvant therapies for OSC and USC may differ. WT‐1 staining patterns also differ between OSC and ovarian endometrioid carcinoma and so it is possible that WT‐1 may assist in the distinction of these two neoplasms, which is sometimes problematic, especially with poorly differentiated tumours. This study aims to document the value of WT‐1 in these settings. Cases of ovarian borderline serous tumour, primary peritoneal serous carcinoma (PPSC) and uterine endometrioid carcinoma were also studied.

Methods and results : Cases of OSC (n = 38), USC (n = 25) (in five of these cases there was also a component of endometrioid adenocarcinoma), ovarian endometrioid carcinoma (n = 13), uterine endometrioid carcinoma (n = 7), ovarian borderline serous tumour (n = 16) and PPSC (n = 6) were stained with WT‐1. Cases were scored on a scale of 0–3, depending on the percentage of positive cells. The intensity of staining was scored as weak, moderate or strong. There was positive nuclear stainingof 36 of 38 (94.7%) OSC with WT‐1. In most OSC (68.4%), >50% of cells stained positively and staining was usually strong. Five of 25 (20%) USC were positive with only two cases exhibiting staining of >50% of cells. All primary ovarian and uterine endometrioid carcinomas were negative. All PPSC were positive, usually with diffuse strong immunoreactivity. Fourteen of 16 borderline serous tumours exhibited positivity with WT‐1.

Conclusions : WT‐1 is useful in distinguishing OSC (characteristically diffuse strong nuclear positivity) from USC (characteristically negative). However, rarely OSC is negative and occasional cases of USC are positive. WT‐1 may also be helpful in differentiating poorly differentiated OSC from poorly differentiated ovarian endometrioid carcinoma.
Accuracy of the determination of S100B protein expression in malignant melanoma using polyclonal or monoclonal antibodies
Authors: Tímár J , Udvarhelyi N , Bánfalvi T , Gilde K , Orosz Zs
Published: December 2004

Aims : To compare the routinely used polyclonal anti‐S100 and a mouse monoclonal anti‐S100B antibody for their accuracy in the detection of the S100B expression profile (pattern and intensity) in a series of 67 primary (n = 37) and lymph node metastatic (n = 30) melanoma tissues. S100B is the lineage marker of malignant melanoma. Antibodies routinely used for melanoma diagnosis are not necessarily specific for this protein. Furthermore, clinical monitoring of melanoma progression is mostly based on the determination of serum S100B protein levels without knowing the actual expression level in the primary and/or metastatic tissue.

Methods and results : The profile of expression patterns (focal, heterogenous and diffuse) as well as intensity ranges (+, ++ and +++) were similar for the two antibodies in melanoma tissues. However, comparison of the patterns and intensities on the basis of individual cases revealed a high frequency of discrepancies (50.7 and 58.2%, respectively). Severe discrepancy between the two antibodies in the determination of the S100B protein expression pattern (focal versus diffuse or focal versus heterogeneous) was relatively frequent; 13.4 and 11.9%, respectively. Furthermore, a similar rate of severe discrepancy was observed between the two antibodies in the determination of the intensity of S100B expression levels (+ versus +++ or + versus ++); 19.4 and 8.9%, respectively. Separate analysis of the primary tumours and metastases gave similar results.

Conclusion : For the accurate determination of S100B protein expression in malignant melanoma it is highly recommended that a monospecific antibody is used.
Preeclampsia is associated with loss of neuronal nitric oxide synthase expression in vascular smooth muscle cells of the human umbilical cord
Authors: Schönfelder G , Fuhr N , Hadzidiakos D , John M , Hopp H , Paul M
Published: December 2004

Aims : Umbilical blood vessels are not innervated and regulation of blood flow to the placenta must depend on structural changes and the effect of vasoactive factors. Failure to achieve these adaptations may result in reduced fetoplacental perfusion. The purpose of this study was to determine whether neuronal nitric oxide synthase (nNOS) is expressed in human vascular smooth muscle cells (VSMCs) of the fetoplacental circulation. nNOS has been described as a non‐endothelial NOS counterregulating vasoconstriction only in the VSMCs of animal models. Therefore, we investigated nNOS expression in the fetoplacental unit from preeclamptic and healthy pregnancies.

Methods and results : We investigated nNOS regulation by immunohistochemistry, Western blotting and reverse transcriptase‐polymerase chain reaction analysis. nNOS activity was determined by measuring the conversion of L‐3H‐arginine to L‐3H‐citrulline. nNOS expression was revealed only in VSMCs of the human umbilical veins, but not in umbilical arteries. A more direct assessment of nNOS activity showed that a small, but consistent amount of nNOS is present in the denuded media of the umbilical vein. In VSMCs of the umbilical veins during preeclampsia a total loss of nNOS protein expression and a significant decrease in mRNA expression were seen.

Conclusions : Loss of nNOS expression is associated with preeclampsia. It may alter the regulation of blood flow in the fetal and maternal placental vasculature in preeclampsia. However, the impact of NO produced by nNOS on the vascular tone of umbilical veins remains to be elucidated.
Microvessel density compared with the Chalkley count in a prognostic study of angiogenesis in breast cancer patients
Authors: Hansen S , Sørensen F B , Vach W , Grabau D A , Bak M , Rose C
Published: December 2004

Aims: Evaluation of angiogenesis by intratumoral vessel profiles can be performed by different methods. The aim of this study was to investigate the prognostic value of estimates obtained by the intratumoral microvessel density (MVD) method and then to compare with corresponding estimates obtained by the Chalkley method.

Methods and results: A total of 330 patients treated for primary, unilateral, invasive breast carcinoma were included. The median follow‐up time was 14 years and 4 months. The microvessels were immunohistochemically stained by antibodies to CD34. MVD was not significantly correlated with any clinicopathological variables. By univariate analysis, MVD showed no prognostic value with regard to recurrence‐free survival (RFS) or overall survival (OS), while the Chalkley count had significant prognostic value (P < 0.0001; RFS and OS). In the Cox multivariate analysis, MVD had no prognostic impact {median HR [confidence interval (CI)] was 0.93 [0.66, 1.32] for RFS; and HR [CI] was 0.86 [0.62, 1.19] for OS}, while the Chalkley count [median HR (CI) was 2.12 (1.48, 3.06) for RFS; and HR (CI) was 1.71 (1.23, 2.37) for OS] provided independent prognostic value when adjusted for age, menopausal status, axillary lymph node status, tumour size, histological grade, adjuvant systemic treatment and radiation therapy. In comparing the results obtained by MVD in our study with those from other published studies we find good agreement.

Conclusions: The Chalkley count technique seems to be preferable for estimating angiogenesis with regard to the prognostic stratification of breast cancer patients, based on its strong prognostic impact, and acceptable reproducibility.
Characteristics of intramucosal gastric carcinoma with lymph node metastatic disease
Authors: Song S Y , Park S , Kim S , Son H J , Rhee J C
Published: December 2004

Aim:  Recent trends in treatment strategy for early gastric cancer (EGC) are towards minimal surgical procedures, such as endoscopic mucosal resection and laparoscopic partial resection. There is a possibility of incomplete removal of regional lymph nodes in minimal procedures, which may subsequently decrease the chance of a cure. Therefore, it is essential to be able to predict lymph node status and to make careful selection of candidates for mucosal resection.

Methods and results:  We studied the relationship between lymph node status and various pathological parameters including macroscopic appearance, location, size, differentiation, presence of ulceration, vascularity, presence of gastritis cystica profunda‐like glandular proliferation, disruption of the muscularis mucosae and invasion into the muscularis mucosae, using age‐ and sex‐matched samples of 40 node‐positive and 80 node‐negative tumours to define the characteristics of intramucosal EGCs. Histological differentiation (P < 0.001), increased submucosal vascularity (P < 0.05), breakdown of the muscularis mucosae (P < 0.05), and invasion of tumour cells into the muscularis mucosae (P < 0.05) were correlated with the lymph node status of intramucosal gastric carcinoma. Furthermore, diffuse type histology (P < 0.001) and deep invasion into the muscularis mucosae (P < 0.05) were indicators of node‐positive intramucosal EGCs.

Conclusions:  These histological indicators are easily accessible and seem to predict lymph node metastatic disease in limited surgical specimens. Patients should be carefully selected despite the recent trend toward less invasive resection of EGCs, especially for those apparently confined to the mucosa.
Microinvasive germ cell tumour (MGCT) adjacent to testicular germ cell tumours
Authors: Von Eyben F E , Jacobsen G K , Rorth M , Von Der Maase H
Published: December 2004

Aims:  To examine the occurrence and prognostic significance of intratubular germ cell neoplasia (IGCN) and microinvasive germ cell tumour (MGCT) in tissue adjacent to testicular germ cell tumours (TGCT) in adults.

Methods and results:  The study was based on two Danish studies of adult patients with stage I TGCT and included 255 patients. Of 106 patients with seminoma, 75 [71%, 95% confidence interval (CI) 61, 79] had IGCN without MGCT and nine (8%, CI 4, 15) had both IGCN and MGCT. Of 149 patients with non‐seminoma, 62 (42%, CI 34, 50) had IGCN without MGCT, and 32 (22%, CI 15, 29) had both IGCN and MGCT. Non‐seminomas with a seminoma component were more often associated with MGCT (23 of 54 testes, 43%, CI 29, 57) than were non‐seminomas without this component (nine of 95 testes, 10%, CI 4, 17) (P < 0.000 05, Fisher's exact test). Relapse‐free survival was not influenced by the concomitant presence of the two precursor stages in the testes (P = 0.36, and P = 0.19, log rank test, respectively).

Conclusions:  MGCT was a relatively frequent finding in testes adjacent to a macroscopic TGCT. However, neither IGCN nor MGCT predicted relapse for patients with stage I TGCT.
High‐grade carcinomas of the breast showing patterns of mixed ductal and myoepithelial differentiation (including myoepithelial cell‐rich carcinoma of the breast)
Authors: Coyne J D , Dervan P A , Barr L
Published: December 2004

Aims:  To assess the clinical, morphological and immunophenotypic characteristics of breast carcinomas showing patterns of mixed epithelial and myoepithelial differentiation.

Methods and results:  Included in the study were four carcinomas containing a mixed population of epithelial and myoepithelial cells identified using morphological features at the light microscopic level which were found amongst a review of 500 archival cases and two recently accessioned cases. The carcinomas varied in size from 20 to 38 mm and all were grade 3 ductal carcinomas. Most showed nodular and sheet‐like cellular aggregates, although one case showed small solid cell aggregates with duct formation. The cells were large, round, polygonal or spindle‐shaped and had areas of clear or eosinophilic cytoplasm in variable proportions. Foci of metaplasic carcinoma were present in three cases. All cases showed strong, patchy positivity for cytokeratin (CK)14, calponin, smooth actin and muscle specific actin. Epithelial membrane antigen and CK8 were positive in a similar proportion of cells. One patient died 23 months following diagnosis with metastatic carcinoma, another patient died of unrelated disease and four patients are alive with follow‐up ranging from 18 months to 25 years.

Conclusions:  High‐grade carcinomas of the breast showing patterns of mixed ductal and myoepithelial differentiation may show additional morphological features such as foci of metaplasia and appear to have a good prognosis similar to myoepithelial cell‐rich carcinomas. However, young age and lymph node metastasis may portend a worse prognosis.
British Division of the International Academy of Pathology
Authors: Van Den Tweel J , Howat A J , Shepherd N A , Francis N , Harris C
Published: December 2004

Spring 2004 Symposium on Dermatopathology. Brussels, Belgium

10‐‐15 October 2004 XXVth International Congress. Brisbane, Australia

26‐‐27 November 2004 Symposium on Pulmonary Pathology. London, UK
Metallothionein expression in human neoplasia
Authors: Theocharis S E , Margeli A P , Klijanienko J T , Kouraklis G P
Published: December 2004

The metallothionein family is a class of low‐molecular‐weight, cysteine‐rich proteins with high affinity for metal ions. Four major isoforms (metallothionein‐1, ‐2, ‐3, and ‐4) have been identified in mammals, involved in many pathophysiological processes, including metal ion homeostasis and detoxification, protection against oxidative damage, cell proliferation and apoptosis, drug and radiotherapy resistance and several aspects of the carcinogenic process. In the present review we examine the expression of metallothionein in different human tumours and its correlation with histopathological variables, tumour cell proliferation or apoptosis, resistance to radiation or chemotherapy, patient survival and prognosis. A variable profile of metallothionein and its isoforms' expression has been observed in different cancer types. Although metallothionein expression has been implicated in carcinogenic evolution, its use as a marker of tumour differentiation, cell proliferation and prognosis predictor remains unclear. Detailed studies focused on the expression of metallothionein isoforms and isotypes in different tumour types could elucidate the role of this group of proteins in the carcinogenic process, delineating its possible clinical significance for the management of patients.
CD10 immunostaining of bile canaliculi in liver biopsies: change of staining pattern with the development of cirrhosis
Authors: Shousha S , Gadir F , Peston D , Bansi D , Thillainaygam A V , Murray‐Lyon I M
Published: December 2004

Aims : This study was prompted by published observations concerning the absence of normal bile canalicular CD10 staining in some cases of primary liver cell carcinoma. Our aim was to investigate the possibility that this loss of staining occurs prior to the development of cancer.

Methods and results : The study comprised 164 liver biopsies, including 96 from patients with hepatitis C infection of various grades and stages including nine cases with cirrhosis, 24 other cases of cirrhosis of other aetiology, five cases of primary liver carcinoma, 12 cases of metastatic carcinoma, as well as biopsies with a variety of other liver diseases. CD10 was demonstrated in paraffin sections using the avidin–biotin immunoperoxidase technique. In hepatitis C cases, a significant loss of the canalicular pattern was seen in four out of 41 (10%) biopsies with stages 0–1 compared with 25 out of 55 (45%) with stages 2–6 (P < 0.001). There was also a significant difference (P < 0.001) between biopsies with stage 2–3 and those with stage 4–6, where marked pattern loss was seen in 9/37 (24%) and 16/18 (89%), respectively. Marked loss of the pattern was also seen in 16 out of the 24 (67%) other cirrhotic biopsies, as well as in cases with severe lobular inflammation and cholestasis and liver cell dysplasia and carcinoma. In hepatitis C biopsies, no relationship was noted between the reduction in the canalicular pattern and the necroinflammatory score.

Conclusions : CD10‐stained bile canalicular pattern in liver biopsies is preserved in cases with mild fibrosis and inflammation, but it becomes increasingly reduced with the advance of fibrosis or the presence of severe lobular inflammation or extensive metastases. Further investigations into the relationship between the changes in CD10 staining pattern and liver function tests may be useful in explaining test results.
The pathology associated with therapeutic procedures in malignant mesothelioma
Authors: Attanoos R L , Gibbs A R
Published: December 2004

Aims : To describe iatrogenic pathological lesions in malignant pleural mesothelioma.

Methods and results : All cases of malignant pleural mesothelioma confirmed by antemortem pleural biopsy and undergoing post mortem examination over a 7‐year period (1995–2001) formed the study group. This comprised 48 malignant pleural mesotheliomas [epithelioid (n = 21), biphasic (n = 14) and sarcomatoid (n = 13)]. Twenty‐eight of 48 (58%) had received chemical (talc) pleurodesis, 30/48 (63%) palliative localized radiotherapy, 6/48 (13%) chemotherapy, and 14/48 (30%) surgery [12/48 (26%) pleural decortication and 2/48 (4%) pleuropneumonectomy].

Conclusions : Talc pleurodesis induces a marked pseudosarcomatous fibroblastic proliferation which may impart a biphasic pattern to the neoplasm. In more chronic cases, paucicellular fibrosis with a foreign body giant cell reaction is noted. The talc is polarizable and deposited in linear fashion within the tumour. In 2/28 (7%) pleurodesis cases platyform ferruginous bodies were seen in the peripheral alveolated lung parenchyma and these mimicked asbestos bodies. An awareness of this is important to prevent false attribution to asbestos. Talc could be identified by transmission electron microscopic mineral analysis in 5/15 (33%) cases examined. Tumour nodules developing subjacent to iatrogenic wound sites were noted in 8/48 (17%) cases. In 6/8 (75%) of these cases, comparative assessment of the locally irradiated subcutaneous chest wall tumour, with background pleural mesothelioma, showed no morphological difference in architectural tumour growth pattern, extent of necrosis, cytological or nuclear pleomorphism, mitotic activity or tumour immunophenotype. In 2/8 (25%) cases the locally irradiated tumour showed prominent bizarre multinucleated tumour giant cells and intense mixed inflammation, a feature not seen in the background (non‐irradiated) tumour. All six malignant pleural mesotheliomas receiving chemotherapy appeared refractory to treatment in that chemotherapy did not appear to have any significant effect on the tumour morphology, cytonuclear pleomorphism, mitotic activity, extent of necrosis or immunophenotype. In the 12 decortication specimens and two pleuropneumonectomy resections, post mortem examination identified evidence of residual malignant mesothelioma of similar morphological subtype and immunophenotype to the resected tumour.