Expression Of Calretinin Research Articles

1533P - Expression of Wilmśtumour Gene (WT1) is Associated with Survival in Malignant Pleural Mesothelioma: Retrospective Analysis in a Single Center Series

ABSTRACT Background Calretinin and Wilmśtumour gene (WT1) are mesothelial markers used to confirm the diagnosis of malignant pleural mesothelioma (MPM). Recently, calretinin score assessed by immunohistochemistry (IHC) was implicated with poor prognosis in MPM. We investigated the prognostic value of calretinin and WT1 expression in predicting survival in a series of patients (p) diagnosed of MPM in our institution Methods Fifty two patients diagnosed of MPM in Vall dHebron University Hospital were retrospectively reviewed. Potential prognostic factors analyzed were age, performance status (PS), neutrophil to lymphocyte ratio (NLR), clinical stage, histology, calretinin and WT1 expression. Survival data were calculated by Kaplan-Meier. Results Patient's characteristics: median age 68 years (31-88 years), males 75.5%, PS 1: 67.3%, asbestos exposure 53.1%, clinical stage III: 55.1%, epithelial subtype 71.4% and NLR > 5 in 44.9% of all patients. Calretinin and WT1 IHC expression were available in 47 p and 32 p, and were positive in 41 p (83.7%) and 25 p (78.1%) respectively. All patients were considered initially unresectable and 71.4% received CT. We found a significant association of calretinin and WT1 expression with epithelial histology (p= 0.030 and p = 0.010). The median survival (OS) was 15.2 months. We found a significant increase in OS in patients with epithelial subtype (23.4 vs 5.0 months in epithelial vs no-epithelial, p Conclusion In our series of 52 MPM patients, epithelial histology, PS, NLR and WT1 expression are significant prognostic factors for survival. The prognostic role of WT1 is worth of prospective validation in future studies on MPM. Disclosure All authors have declared no conflicts of interest.

Seminoma, Sertolioma, and Leydigoma in Dogs: Clinical and Morphological Correlations

Abstract The study aimed at presenting the most frequent male gonadal tumours in dogs, their clinical and histopathological aspects, at outlining aetiopathogenesis and differential diagnosis of the tumours. As examples of the most frequently manifested testicular tumours, three clinical cases were presented, involving tumour of interstitial (Leydig) cells, tumour of Sertoli cells, and seminoma. Respective clinical diagnosis employed USG, X-ray patterns, and morphological and biochemical tests. The surgically sampled material was stained with H+E and an attempt was made to establish expression of E-cadherin, calretinin, and Ki-67. It was shown that histopathological diagnosis of testicular tumours in dogs is frequently very difficult and complex and requires multidirectional studies.

Regional distribution of calretinin and calbindin-D28k expression in the brain of the urodele amphibian Pleurodeles waltl during embryonic and larval development

The sequence of appearance of calretinin and calbindin-D28k immunoreactive (CRir and CBir, respectively) cells and fibers has been studied in the brain of the urodele amphibian Pleurodeles waltl. Embryonic, larval and juvenile stages were studied. The early expression and the dynamics of the distribution of CBir and CRir structures have been used as markers for developmental aspects of distinct neuronal populations, highlighting the accurate extent of many regions in the developing brain, not observed on the basis of cytoarchitecture alone. CR and, to a lesser extent, CB are expressed early in the central nervous system and show a progressively increasing expression from the embryonic stages throughout the larval life and, in general, the labeled structures in the developing brain retain their ability to express these proteins in the adult brain. The onset of CRir cells primarily served to follow the development of the olfactory bulbs, subpallium, thalamus, alar hypothalamus, mesencephalic tegmentum, and distinct cell populations in the rhombencephalic reticular formation. CBir cells highlighted the development of, among others, the pallidum, hypothalamus, dorsal habenula, midbrain tegmentum, cerebellum, and central gray of the rostral rhombencephalon. However, it was the relative and mostly segregated distribution of both proteins in distinct cell populations which evidenced the developing regionalization of the brain. The results have shown the usefulness in neuroanatomy of the analysis during development of the onset of CBir and CRir structures, but the comparison with previous data has shown extensive variability across vertebrate classes. Therefore, one should be cautious when comparing possible homologue structures across species only on the basis of the expression of these proteins, due to the variation of the content of calcium-binding proteins observed in well-established homologous regions in the brain of different vertebrates.

Transient Appearance of Tyrosine Hydroxylase Immunoreactive Cells in the Midline Epithelial Seam of the Human Fetal Secondary Palate

Transient immunoreactivity for tyrosine hydroxylase, which mediates the conversion of the amino acid L-tyrosine to dihydroxyphenylalanine, in the midline epithelial seam between the bilateral palatal shelves was investigated in human fetuses. Horizontal or frontal paraffin sections of two human fetuses at 9 and 15 weeks of gestation were used to examine the distribution of tyrosine hydroxylase-immunoreactive cells in regions of the entire head other than the brain. Immunohistochemical staining for S100 protein, calretinin, cytokeratin 14, and vimentin was examined using adjacent or near sections. Tyrosine hydroxylase-immunoreactive cells were large and densely distributed in the midline epithelial seam at the site of palatal fusion in fetuses at 9 weeks but not in fetuses at 15 weeks, in which the midline epithelial seam had already disappeared. No expression of S100 protein, calretinin, or vimentin was detected, but the midline epithelial seam was positive for cytokeratin 14. Tyrosine hydroxylase immunoreactivity was not detected in epithelia during the process of palatal fusion in mice from E 14.0 to 15.0. These findings indicate that tyrosine hydroxylase-immunoreactive cells in the midline epithelial seams are nonneural epithelial cells and suggest that the tyrosine hydroxylase is a novel factor involved in normal palatal formation, especially the fate of the midline epithelial seam in humans.

Prenatal dexamethasone selectively decreases calretinin expression in the adult female lateral amygdala

Exposure to high levels of glucocorticoids (GCs) during early development results in lasting disturbances in emotional behavior in rodents. Inhibitory GABAergic neurons, classified by their expression of calcium binding proteins (CBPs), also contribute to stress-related behaviors and may be GC sensitive during development. Therefore, in the present study we investigated the effects of prenatal treatment with the glucocorticoid receptor agonist dexamethasone (DEX) on expression of calbindin and calretinin in brain areas critical to emotional regulation (basolateral/lateral amygdala and hippocampal CA1 and CA3 regions). Late gestational treatment with DEX (gestational days 18–22) significantly decreased the density of calretinin immunoreactive cells in the lateral amygdala of adult female offspring with no differences in the basolateral amygdala, hippocampal CA1, or CA3 regions. Moreover, there were no effects of gestational DEX treatment on calretinin expression in males. Calbindin expression in adulthood was unaltered within either amygdala or hippocampal subregion of either sex following prenatal DEX treatment. Together these findings indicate that late gestational DEX treatment causes a targeted reduction of calretinin within the lateral amygdala of females and this may be one mechanism through which developmental glucocorticoid exposure contributes to lasting alterations in emotional behavior.

Glutamatergic projection from the nucleus incertus to the septohippocampal system

Recent findings support a relevant role of the nucleus incertus in the control of the hippocampal activity through the modulation of theta rhythm. Previous studies from our group have shown that this nucleus is a critical relay between reticularis pontis oralis and the medial septum/diagonal band, regarded as the main activator and the pacemaker of the hippocampal oscillations, respectively. Besides, the nucleus incertus is highly linked to activated states related to the arousal response.The neurotransmission of the nucleus incertus, however, remains uncertain. Only GABA and the neuromodulator relaxin 3 are usually considered to be involved in its contribution to the septohippocampal system. In this work, we have analyzed the existence of an excitatory projection from the nucleus incertus to the medial septum. We have found a group of glutamatergic neurons in the nucleus incertus projecting to the medial septum. Moreover, we were able to describe a segregated distribution of calbindin and calretinin neurons. While calretinin expression was restricted to the nucleus incertus pars compacta, calbindin positive neurons where observed both in the pars dissipata and the pars compacta of the nucleus.The present work provides innovative data supporting an excitatory component in the pontoseptal pathway.

The changes of calretinin immunoreactivity in paraquat-induced nephrotoxic rats

Calcium-binding proteins are present in the kidneys: calbindin D-28k in the distal tubules and calretinin in the proximal tubules. Since paraquat causes degeneration in the brush border-bearing proximal tubule cells in rat kidneys, we investigated the changes of calretinin immunoreactivity in the proximal tubule cells of paraquat-induced nephrotoxicity in experimental male Sprague-Dawley rats following chitosan oligosaccharide pretreatment to investigate its protective properties. Paraquat (60mg/kg) was administered intraperitoneally with or without chitosan oligosaccharide (500mg/kg, p.o.) pretreatment. The changes on calretinin were compared with those of calbindin D-28k by immunohistochemistry and Western Blot analysis. Calretinin was immunolocalized on the apical surface of proximal tubule cells in the deeper cortex of normal kidney, and disappeared after paraquat administration with minor changes of calbindin D-28k immunoreactivity in the distal tubules and collecting ducts. Chitosan oligosaccharide pretreatment caused increased expression of calretinin and calbindin D-28k before paraquat injection and helped preserve proximal tubules after paraquat treatment. However, Western blot analysis on calretinin and calbindin D-28k could not explain the degeneration of the proximal tubule cells in paraquat-induced nephrotoxicity. These findings suggested that calretinin is a possible and more useful histopathological marker for proximal tubule cells in paraquat-induced nephrotoxic rats.

Subpopulations of cholinergic, GABAergic and glutamatergic neurons in the pedunculopontine nucleus contain calcium‐binding proteins and are heterogeneously distributed

Neurons in the pedunculopontine nucleus (PPN) are highly heterogeneous in their discharge properties, their neurochemical markers, their pattern of connectivity and the behavioural processes in which they participate. Three main transmitter phenotypes have been described, cholinergic, GABAergic and glutamatergic, and yet electrophysiological evidence suggests heterogeneity within these subtypes. To gain further insight into the molecular composition of these three populations in the rat, we investigated the pattern of expression of calcium binding proteins (CBPs) across distinct regions of the PPN and in relation to the presence of other neurochemical markers. Calbindin- and calretinin-positive neurons are as abundant as cholinergic neurons, and their expression follows a rostro-caudal gradient, whereas parvalbumin is expressed by a low number of neurons. We observed a high degree of expression of CBPs by GABAergic and glutamatergic neurons, with a large majority of calbindin- and calretinin-positive neurons expressing GAD or VGluT2 mRNA. Notably, CBP-positive neurons expressing GAD mRNA were more concentrated in the rostral PPN, whereas the caudal PPN was characterized by a higher density of CBP-positive neurons expressing VGluT2 mRNA. In contrast to these two large populations, in cholinergic neurons expression of calretinin is observed only in low numbers and expression of calbindin is virtually non-existent. These findings thus identify novel subtypes of cholinergic, GABAergic and glutamatergic neurons based on their expression of CBPs, and further contribute to the notion of the PPN as a highly heterogeneous structure, an attribute that is likely to underlie its functional complexity.

Expression of p16, p53, CD24, EpCAM and Calretinin in Serous Borderline Tumors of the Ovary

According to the widely accepted pathway, a serous borderline tumor becomes invasive either by progressing into a noninvasive micropapillary tumor or directly through microinvasion. Our objective was to investigate the role of serous borderline tumors and their accompanying extraovarian lesions in pathogenesis of serous ovarian cancer using immunohistochemistry as a tool. An immunohistochemical panel of p16, p53, CD24, EpCAM and calretinin was applied to cutting edge matrix assembly-like tissue arrays of 46 cases consisting of typical, focal micropapillary, micropapillary, microinvasive, cystadenoma, and low-grade carcinoma cases. These tissue arrays are better choices than conventional tissue arrays to examine thin walled and heterogenous neoplasia like serous borderline tumors as they facilitate the analysis with linear sections rather than a core. For two tumor supressor gene markers; no diffuse and strong expression of p53, and strong and patchy/heterogenous expression of p16 were detected in all cases. Focal and strong calretinin expression was detected in micropapillary tumors while expression of EpCAM was lost in the same areas. Strong cytoplasmic CD24 expression was detected in cases with peritoneal implants, favoring the theory that change of expression localization of cell adhesion molecules is in accordance with phenotypical changes and tumor progresssion. Furthermore, circumfrential membranous and cytoplasmic expression of CD24 and EpCAM was detected in neoplastic cells in lymph nodes and microinvasion areas. Our results show that different levels of serous ovarian tumor progression are accompanied by changes in the immunohistochemical expression pattern of EpCAM, CD24, and calretinin.

The value of the expressions of E-cadherin, Calretinin and GLUT-1 in the differential diagnosis of malignant mesothelioma, reactive mesothelial proliferation and adenocarcinoma in serous effusions

The value of the expressions of E-cadherin, Calretinin and GLUT-1 in the differential diagnosis of malignant mesothelioma, reactive mesothelial proliferation and adenocarcinoma in serous effusions

5-HT3AReceptor-Bearing White Matter Interstitial GABAergic Interneurons Are Functionally Integrated into Cortical and Subcortical Networks

In addition to axons and surrounding glial cells, the corpus callosum also contains interstitial neurons that constitute a heterogeneous cell population. There is growing anatomical evidence that white matter interstitial cells (WMICs) comprise GABAergic interneurons, but so far there is little functional evidence regarding their connectivity. The scarcity of these cells has hampered electrophysiological studies. We overcame this hindrance by taking recourse to transgenic mice in which distinct WMICs expressed enhanced green fluorescence protein (EGFP). The neuronal phenotype of the EGFP-labeled WMICs was confirmed by their NeuN positivity. The GABAergic phenotype could be established based on vasoactive intestinal peptide and calretinin expression and was further supported by a firing pattern typical for interneurons. Axons and dendrites of many EGFP-labeled WMICs extended to the cortex, hippocampus, and striatum. Patch-clamp recordings in acute slices showed that they receive excitatory and inhibitory input from cortical and subcortical structures. Moreover, paired recordings revealed that EGFP-labeled WMICs inhibit principal cells of the adjacent cortex, thus providing unequivocal functional evidence for their GABAergic phenotype and demonstrating that they are functionally integrated into neuronal networks.

Expression of calretinin by breast carcinoma and the potential for misdiagnosis of mesothelioma

Calretinin and cytokeratin (CK)5/6 are frequently used to differentiate between metastatic breast cancer and primary malignant mesothelioma in pleural biopsies, but both tumours may express these markers. This study was aimed at evaluating the frequency of calretinin expression in primary breast carcinomas, and assessing the characteristics of the calretinin-positive tumours. Fifty-three primary breast adenocarcinomas were analysed for immunohistochemical expression of calretinin. CK5/6 and epidermal growth factor receptor (EGFR) immunostaining were performed on the calretinin-positive subset. Tumours were classified as basal-like if they met standard morphological and immunohistochemical criteria. Fifteen per cent (8/53) of the breast tumours were positive for calretinin. Eighty-eight per cent (7/8) of the calretinin-positive tumours were grade 3, as compared with 20% (9/45) of the calretinin-negative tumours (P<0.001). Only 13% (1/8) of the calretinin-positive tumours were also oestrogen receptor (ER)-positive, as compared with 87% (39/45) of the calretinin-negative tumours (P<0.001). Eleven per cent (6/53) of the tumours were classified as basal-like. Of these, four were positive for calretinin and two were negative (P=0.003). Fifteen per cent of breast carcinomas stain with calretinin. These tumours are more likely to be high-grade, ER-negative, and display a basal-like phenotype. These tumours may be misdiagnosed as malignant mesothelioma when they metastasize to the pleura.

Low Calretinin Expression and High Neutrophil-To-Lymphocyte Ratio Are Poor Prognostic Factors in Patients with Malignant Mesothelioma Undergoing Extrapleural Pneumonectomy

Survival after extrapleural pneumonectomy (EPP) is variable in patients with malignant pleural mesothelioma (MPM), and there are no validated prognostic factors that could be used preoperatively. We investigated the calretinin and D2-40 expression and the neutrophil-to-lymphocyte ratio (NLR), an index of systemic inflammation as potential preoperative prognostic factors. Consecutive patients who underwent EPP were included in this retrospective study. Potential prognostic factors such as age, gender, histological subtype, baseline laboratory parameters including NLR, and immunohistochemical staining for calretinin and D2-40 were evaluated. Overall survival (OS) from the date of surgery was determined by the Kaplan-Meier method. The prognostic value of the variables was examined using Cox regression, and significant factors (p < 0.05) were entered into a multivariate model to determine their independent effect. A total of 85 patients were included: median age 58 years; 80% men; 77% epithelial and 23% biphasic MPM. The median OS was 19.7 months. The following variables were predictive of longer OS: female gender (p = 0.02), epithelial subtype (p = 0.04), low NLR (p < 0.01), and high calretinin score (p < 0.001). In a multivariate analysis, only NLR ≥3 (hazard ratio 1.79; 95% confidence interval: 1.04-3.07; p = 0.04) and calretinin score ≤33 versus more than 67% (hazard ratio 4.72; 95% confidence interval: 1.97-11.32; p < 0.01) remained independent predictors. The addition of calretinin score increased the explained variation by 10.1%. Both low calretinin expression and high NLR were independently associated with poor prognosis in patients with MPM undergoing EPP, and the calretinin score seemed to improve the accuracy of the prognostic model.

Targeted deletion of Hand2 in enteric neural precursor cells affects its functions in neurogenesis, neurotransmitter specification and gangliogenesis, causing functional aganglionosis

Targeted deletion of the bHLH DNA-binding protein Hand2 in the neural crest, impacts development of the enteric nervous system (ENS), possibly by regulating the transition from neural precursor cell to neuron. We tested this hypothesis by targeting Hand2 deletion in nestin-expressing neural precursor (NEP) cells. The mutant mice showed abnormal ENS development, resulting in lethal neurogenic pseudo-obstruction. Neurogenesis of neurons derived from NEP cells identified a second nestin non-expressing neural precursor (NNEP) cell in the ENS. There was substantial compensation for the loss of neurons derived from the NEP pool by the NNEP pool but this was insufficient to abrogate the negative impact of Hand2 deletion. Hand2-mediated regulation of proliferation affected both neural precursor and neuron numbers. Differentiation of glial cells derived from the NEP cells was significantly decreased with no compensation from the NNEP pool of cells. Our data indicate differential developmental potential of NEPs and NNEPs; NNEPs preferentially differentiate as neurons, whereas NEPs give rise to both neurons and glial cells. Deletion of Hand2 also resulted in complete loss of NOS and VIP and a significant decrease in expression of choline acetyltransferase and calretinin, demonstrating a role for Hand2 in neurotransmitter specification and/or expression. Loss of Hand2 resulted in a marked disruption of the developing neural network, exemplified by lack of a myenteric plexus and extensive overgrowth of fibers. Thus, Hand2 is essential for neurogenesis, neurotransmitter specification and neural network patterning in the developing ENS.

The effect of different maternal deprivation paradigms on the expression of hippocampal glucocorticoid receptors, calretinin and calbindin-D28k in male and female adolescent rats

Maternal deprivation (MD) is a well-established protocol used to investigate neurobiological changes that are associated with the etiology of and vulnerability to stress-related diseases in animal models. The resulting psychophysiological effects, the timing and duration of these adverse stimuli, and the method by which they exert their effects on the animals remain unclear. This study characterized differences in the hippocampal expression of glucocorticoid receptors (GRs) and the calcium-binding proteins calretinin (CALR) and calbindin-D28k (CALB) in male and female rats that underwent different MD paradigms during the stress hyporesponsive period (SHRP). Both GRs and the two calcium-binding proteins were much more abundant in females than in males. MD paradigms had a significant effect on CALR and CALB expression in both males and females but affected GR levels only in males. Additionally, expression of the two calcium-binding proteins in the hippocampus responded differently to MD-induced stress, especially in females. Taken together, these results indicate that females are able to modulate their response to stress better than males.

Effect of Ginseng on Calretinin Expression in Mouse Hippocampus Following Exposure to 835 MHz Radiofrequency

Exponential rise in the use of mobile communication devices has generated health concerns due to radiofrequency (RF) exposure due to its close proximity to the head. Calcium binding proteins like calretinin regulate the levels of calcium (Ca2+) which plays an important role in biological systems. Ginseng is known for maintaining equilibrium in the human body and may play a beneficial radioprotectant role against electromagnetic field (EMF) exposure. In the present study, we evaluated the radioprotective effects of red ginseng (RG) extract in a mouse model. Calretinin (CR) expression was measured using a free-floating immunohistochemical method in the hippocampus of mice after 835 MHz EMF exposure for 5 h/d for 5 d at specific absorption rate=1.6 W/kg for the different experimental groups. The control animals were treated with NaCl while the experimental animals received 10 mg/kg ginseng, or 30 mg/kg; EMF exposed mice were also treated with NaCl, 10 mg/kg ginseng (E10), or 30 mg/kg (E30). Decreases in CR immunoreactivity (IR) along with loss of CA1 and CA3 interneurons and infragranular cells were observed in the ENaCl group while such losses were not observed in the E10 and E30 groups. CR IR significantly increased in the RG-treated group compared to control and EMF-exposed groups treated with NaCl. The study demonstrates that RG extract can serve as a radioprotective agent that maintains Ca2+ homeostasis and prevents neuronal loss in the brain hippocampal region caused by RF exposure.

The prognostic role of calretinin expression and neutrophil-to-lymphocyte ratio (NLR) in patients with malignant pleural mesothelioma (MPM) undergoing extrapleural pneumonectomy (EPP).

10545 Background: Survival after EPP is variable. Currently there are no validated prognostic factors that can be used to select patients for this procedure. We have investigated the expression of calretinin and D2-40, both associated with tumour differentiation, as well as NLR, an index of systemic inflammatory response as potential preoperative prognostic factors for patients undergoing EPP. Methods: All MPM patients who underwent EPP at participating institutes were included in this retrospective study. Potential prognostic factors such as age, gender, histological subtype, baseline laboratory parameters (white blood cell and platelet count, hemoglobin, and NLR), and immunohistochemical expression of calretinin and D2-40 (scored based on percentage of cells labeled) were evaluated. Overall survival (OS) from the date of surgery was determined by the Kaplan Meier method. The prognostic value of the variables was examined using Cox regression and significant factors (p<0.05) were entered into a multivariate model together to determine their independent effect. Results: A total of 85 patients were included: median age 58 years (range: 22-74); 80% male; 77% epithelial and 23% biphasic MPM. The median OS was 19.7 months (95% CI: 13.8 – 25.6). The following variables were predictive of longer OS: female gender (p=0.02), epithelial histological subtype (p=0.04), low NLR (p<0.01), and high calretinin score (p<0.001). The median OS was 26.7 months vs. 12.6 months for NLR <3 and ≥3 respectively, while it was 35.8 vs. 14.5 vs. 6.9 months for calretinin scores >67%, 34-67% and ≤33% respectively. After multivariate analysis, NLR ≥3 (HR 1.79; 95% CI, 1.04-3.07; p=0.04), and calretinin score ≤33% vs. >67% (HR 4.72; 95% CI, 1.97-11.32; p<0.01) remained independent predictors. Conclusions: Low calretinin expression (poorly differentiated tumours) and high NLR (exaggerated systemic inflammatory response) were independently associated with poor prognosis in MPM patients undergoing EPP. Both calretinin and full blood counts are routinely available and their prognostic value should be validated in a prospective manner.

Fetal head anomaly restricted to the eye, the mandible, and the pterygoid process of the sphenoid: A histological study

A report on an unusual combination of anomalies in the head of a female fetus. The authors examined whole body semiserial paraffin sections of a female fetus (155 mm CRL; ∼18 weeks of gestation), with a particular focus on the head region. Cranial autonomic ganglia, nasal olfactory cells, and the orbital muscle were investigated using immunohistochemistry for tyrosine hydroxylase, vasoactive intestinal peptide, calretinin, and smooth muscle actin expression. The surface gross anatomy of the fetus appeared normal. The left eyeball lacked a lens (the eyeballs were otherwise normal). The orbital muscle was very thick and located in the anterolateral side of the extraocular muscles. Conversely, the extraocular muscles made a cluster in the superoposterior side of the orbit. The infratemporal fossa was small due to the bulky, transversely extended lateral pterygoid process in contrast to the small coronoid process of the mandible. The bilateral mandibular bases overlapped at the midline symphysis. The thin orbitosphenoid and thick alisphenoid provided an almost flat, anterior cranial base. Nasal olfactory cells and cranial autonomic ganglia appeared to be normal. No major anomaly was observed in the brain. Because of the changes in topographical anatomy, the orbital muscle probably lost its normal bony attachment and appeared to push the extraocular muscles superoposteriorly. A gene function redundancy rather than mutation may explain the present restricted anomalies in the mandible and pterygoid process.

Adenomatoid tumors of the female and male genital tract. A comparative clinicopathologic and immunohistochemical analysis of 47 cases emphasizing their site-specific morphologic diversity

Adenomatoid tumors (ATs) are uncommon benign mesothelial tumors with a predilection for the genital tract. We reviewed 47 ATs diagnosed at our institutions during 10-year period. Thirty tumors (64%) originated in the female (21 uterine, 8 tubal, and 1 ovarian) and 17 (36%) in the male (9 epididymal and 8 testicular) genital tract. The median age for females and males was 47.5 and 51 years, respectively. While 83% of tumors in females were incidental findings in resections for unrelated diseases, 94% of male lesions presented as clinical masses leading to surgery. The median size was 2, 1, and 0.5 cm for uterine, epididymo-testicular, and tubo-ovarian lesions, respectively. Architecturally, the microcystic/angiomatoid pattern was the most frequent (32/47; 68%), followed by combined microcystic/trabecular (26/47; 55%) and retiform/adenoid (15/47; 32%) pattern. The trabecular/solid (6%) and macrocystic (4%) patterns were uncommon. However, 57% of cases revealed ≥2 growth patterns. Taken by anatomic site, 20 of 21 uterine cases were at least focally microcystic but none was retiform. In contrast, the retiform pattern dominated in male genital tract tumors (12/17; 71%). Immunohistochemistry showed expression of calretinin (36/36) and D2-40 (30/30) and lack of CD34 (0/30) and PAX8 (0/32). GLUT-1 was expressed in 11/11 male genital tract tumors but in none of the microcystic uterine lesions. Estrogen and progesterone receptor expression was weak and focal (two and three uterine cases, respectively). None stained for the androgen receptor. Our study illustrates the great site-specific morphological diversity of ATs emphasizing their wide site-dependent differential diagnosis.

Aberrant Calretinin and D2-40 Expression in Krukenberg Tumor (HER2/neu Amplified)

Aberrant Calretinin and D2-40 Expression in Krukenberg Tumor (HER2/neu Amplified)