Frame shift mutation of LHX1 is associated with Mayer-Rokitansky-Kuster-Hauser (MRKH) syndrome.

BACKGROUND: The Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome is characterized by congenital aplasia of the uterus and the upper part of the vagina in women who usually have normal ovaries and a 46, XX karyotype. MRKH can occur as an isolated form (type I) or in combination with various malformations as a syndromic or a type II MRKH. To date, in most of the cases the underlying etiology remains unclear. Recently, in approximately 6% of MRKH patients, deletions of chromosomal region 17q12 have been identified. The LHX1 gene, which is located in the deletion interval, has been suggested to be a strong candidate, because targeting inactivation of Lhx1 causes a complex phenotype including aplasia of the Müllerian ducts. METHODS AND RESULTS: By sequence analysis of LHX1 in a large cohort of MRKH patients, we detected a heterozygous frame shift mutation resulting in a premature stop codon. Previously, we have reported a heterozygous missense mutation of LHX1 in another MRKH patient. CONCLUSIONS: We conclude that heterozygous mutations of LHX1 might be one cause of the MRKH syndrome in a subgroup of patients.

MMP-9 expression in meningiomas: a prognostic marker for recurrence risk?

Despite total macroscopic resection of meningiomas relapses do occur in these tumours, possibly because of microscopic clusters of neoplastic cells left in the dura mater or in the arachnoid membrane. The invasiveness of the neoplastic cells of human meningiomas has been related to expression of matrix-metalloproteinase-9 (MMP-9), a peptidase actively implicated in the degradation of the extracellular matrix; nonetheless, the prognostic value of MMP-9 in the risk of recurrence of meningiomas has not been sufficiently investigated. Herein, we analysed MMP-9 expression in a series of meningiomas of different histotype and histological grade and assessed its correlation with various clinico-pathological indicators and with the clinical outcome of these tumours. We also tested the eventual pro-angiogenic role of MMP-9 expression in meningiomas through its correlation with vascular endothelial growth factor (VEGF) and microvessel density (MVD) revealed in the same cases. MMP-9 expression was observed in 64% of cases; high expression of this protein was significantly associated with high histological grade and proliferation index, but not with high MVD, of the tumours. A trend towards correlation between MMP-9 and VEGF expression was found, although statistical significance was not reached. In addition, high MMP-9 expression was a negative independent prognostic factor associated with higher recurrence risk in totally resected meningiomas. In conclusion, we demonstrated for the first time the potential prognostic value of MMP-9 expression in meningiomas. Inhibition of MMP-9 may be a new therapeutic strategy to prevent recurrences of meningiomas, particularly the high-grade type.

The cell growth inhibitory transcription factor C/EBPdelta is expressed in human meningiomas in association with low histological grade and proliferation index.

CCAAT/enhancer binding protein (C/EBP) delta is a transcription factor which has been demonstrated to mediate the growth arrest of mammary and prostate cancer cell lines. It is induced by several stimuli including inflammatory cytokines. In this study, C/EBPdelta immunohistochemical expression was assessed in 49 meningiomas of different histotype and grade and correlated with a variety of clinico-pathological data and with the overall and recurrence-free survival of the patients. Positive staining was observed in the nuclei of neoplastic cells in 22 out of the 49 cases analyzed. C/EBPdelta expression was significantly associated with a low histological grade and proliferation index, reflected by low Ki-67 labeling index (LI) and mitotic activity, and with the presence of intra-tumoral inflammatory infiltrate and the absence of necrosis. In addition, the absence of C/EBPdelta was significantly correlated with a shorter disease-free interval. Our findings suggest that C/EBPdelta expression may prevent the development of recurrences by inhibition of neoplastic growth in meningiomas. If further studies confirm its induction by inflammatory mediators, this might be exploited in novel therapies to prevent recurrences in meningiomas.

NGAL immunohistochemical expression in brain primary and metastatic tumors.

A significant association has been recently shown between the expression of neutrophil gelatinase-associated lipocalin (NGAL) in tumors and its urinary levels. Thus NGAL urinary detection has been proposed as a method for the early diagnosis of brain tumors. In view of this, the objective of this study was to investigate whether NGAL expression differs according to brain tumor type or in primary vs. metastatic brain neolasias. 42 surgically resected formalin fixed and paraffin embedded neoplasias, including 15 cases of brain metastasis and 27 cases of primary central nervous system (CNS) tumors (11 meningiomas; 1 pilocytic astrocytoma, 2 diffuse astrocytomas, 2 oligoastrocytomas, 2 oligodendrogliomas, 1 anaplastic oligoastrocytoma, 7 glioblastomas, 1 ependymoma) were submitted to the immunohistochemical procedure. Sections were incubated overnight with the primary antibody against NGAL. NGAL staining was found in all the analyzed glioblastomas and in the anaplastic oligoastrocytoma. No NGAL immuno-expression was evidenced in all the other cases. A statistically significant correlation was demonstrated between NGAL presence and high proliferation index in the primary tumors. In conclusion, our findings suggest that NGAL expression is restricted to high grade gliomas among primary brain tumors, and that brain metastases do not express this protein. Considering the correlation between NGAL expression in tumors and its urinary levels, if our observations will be further validated, NGAL urinary detection might be used as an additional tool in the pre-surgical definition of brain lesions involving difficult differential diagnosis.

Serum hepatocyte growth factor is increased in Hashimoto's thyroiditis whether or not it is associated with nodular goiter as compared with healthy non-goitrous individuals.

BACKGROUND: Some growth factors and cytokines are known to cooperate with TSH in thyroid nodular growth, but few data are available on their circulating levels in Hashimoto's thyroiditis (HT). AIM: To evaluate in HT patients whether thyroid nodules are associated with variations in serum levels of hepatocyte growth factor (HGF) and interleukin-6 (IL-6). SUBJECTS AND METHODS: Serum levels of HGF and IL-6 were measured by enzyme-linked immunosorbent assay in 176 euthyroid subjects, subdivided into 4 groups: A) HT patients with nodular goiter (no.=42); B) non-goitrous HT patients (no.=36); C) non-HT patients with nodular goiter (no.=48), and D) healthy subjects without thyroid disease (no.=50). RESULTS: The highest concentrations of serumHGF were found in patients with nodular goiter, irrespective of the presence of associated HT (groups A and C). Nevertheless, in group A serum HGF levels were significantly higher than in group C (860.8+/-333.6 pg/ml vs 691.5+/-156 pg/ml, p<0.01). Moreover, though serum HGF levels in group B (578.3+/-217 pg/ml) were lower than in group A, they were significantly higher than in healthy controls (group D, 512.7+/-170.4 pg/ml, p<0.001). Serum IL-6 levels were similar in the two HT groups (A and B), and increased with respect to groups C and D. CONCLUSIONS: Serum HGF is increased in HT, especially associated to thyroid nodules, as compared with healthy non-goitrous individuals.

The Effect of Vibrotactile Feedback on ErrP-based Adaptive Classification of Motor Imagery.

This work presents an implementation of Error-related Potential (ErrP) detection to produce progressive adaptation of a motor imagery task classifier. The main contribution is in the evaluation of the effect of vibrotactile feedback on both ErrP and motor imagery detection. Results confirm the potential of self-adaptive techniques to improve motor imagery classification, and support the design of vibratory and in general tactile feedback into Brain-Computer Interfaces to improve both static and adaptive performance.

Expression of hepatocyte growth factor in Hashimoto's thyroiditis with nodular lesions.

Hashimoto's thyroiditis (HT) is an autoimmune thyroid disease frequently associated with hyperplastic nodules (HN)s. Hepatocyte growth factor (HGF) is expressed in benign thyroid nodules and over-expressed in malignant thyroid nodules, particularly in papillary thyroid carcinomas. To elucidate the role of HGF in the development of HNs in association with HT we evaluated, by immunohistochemistry, the expression of HGF in both nodular and extranodular tissues, obtained from 30 HTs and 15 goiter samples. Six normal thyroid glands were used as controls. All normal control tissue samples exhibited no evidence of HGF immunoreaction. HNs showed weak to moderate HGF immunoreaction, which was located exclusively in the cytoplasm of stromal cells (fibroblasts and endothelial cells). However, the percentage of positive cases was higher in HNs arisen in the context of HT, compared to HNs not associated with HT (30/30 or 100% vs 4/15 or 40%; p<0.001). HGF immunoreactivity was also detected in all extranodular tissues from HT specimens (30/30 or 100%), but we found some significant differences. In fact, while in HNs observed in the context of HT lesions HGF was expressed only in stromal cells, in the extranodular tissues from the same thyroid gland affected by HT it was also detected in the cytoplasm of the epithelial follicular cells. Furthermore, HTs showed a much higher HGF staining grade in the extranodular tissue compared to HNs. Finally, a clear positive correlation was observed in HT between the proportion of HGF expressing follicular cells and the grade of lymphoid aggregates of the thyroid gland. In conclusion, HGF is much more frequently and highly expressed in thyroid tissue with HT, compared to goiter. In HT glands HGF can be detected in both follicular thyroid cells and stromal cells, while in HNs, either from goiters or associated with HT, its expression is restricted only to the stromal cells. These data indicate that HGF may play a role in cell proliferation processes occurring in thyroid glands affected by HT, probably under the regulation of the lymphoid infiltrate.

Quantity of AgNORs in gastric endocrine carcinoid tumours as a potential prognostic tool.

In order to assess if the quantity of silver-stained nucleolar organizer region (AgNOR) proteins represents a prognostic tool in gastric carcinoids, a standardised AgNOR analysis was performed on 24 samples collected from the pathology archives of the Universities of Messina and Parma; the samples were taken at surgery from 11 males and 13 females (mean age 55 yrs, age range 28-77 yrs); 13 cases were defined as Type I, 1 case as Type II and 10 cases as Type III; 16 cases showed a diameter <1 cm, 8 >1 cm. Only 6 tumours were deeply invasive, breaking through the muscularis propria or the subserosa. The proliferative status of carcinoids performed by Ki67 protein antibodies was available in 20/24 cases. The quantification of AgNORs was performed according to the guidelines of the Committee on AgNOR Quantification and the mean area (microm2) of AgNORs per nucleus (NORA) was determined by means of image analyser and specific software programs. The relationship between NORA values and Ki67 data was investigated by Spearman correlation test. The mean NORA value of all 24 gastric carcinoids was 1.279 microm2 (SD 0.404); values ranged from 0.734 to 2.142 microm2. A significantly higher (p < 0.001) mean NORA value (1.736 microm2; SD 0.283) was found in tumours larger than 1 cm, in comparison to the smaller neoplasms (1.051 microm2; SD 0.214); moreover, cases showing deep wall invasion exhibited a mean NORA value of 1.765 microm2 (SD 0.276), significantly higher (p < 0.001) than those with superficial growth (1.118 microm2; SD 0.296). Finally, a similar highly significant difference was seen between type III carcinoids (1.615 microm2; SD 0.375) and type I-II (1.040 microm2; SD 0.208). A linear relationship between Ki67 and corresponding NORA values was obtained by the Spearman correlation test (p = 0.001). No other significant correlations were found between mean NORA values and other clinico-pathological parameters. The AgNOR method seems to be an additional tool potentially able to predict the prognosis of this kind of endocrine tumour, facilitating the identification of fast-growing tumours and being able to directly correlate with the size, deep invasion of gastric wall and tumour type, generally considered as the best prognostic indicators.

Relationship between immunoexpression of mucin peptide cores MUC1 and MUC2 and Lauren's histologic subtypes of gastric carcinomas.

Laurèn's system subdivides gastric cancers into an intestinal type and a diffuse type. This histological classification mirrors histogenetic hypotheses according to which the intestinal-type cancer derives from intestinal metaplasia and dysplasia, while the diffuse-type originates directly from gastric mucosa, with or without a preceding non-metaplastic dysplasia. Studies concerning mucins expression in gastric neoplastic and preneoplastic lesions have provided contradictory data concerning such histogenetic relationships. The aim of the present study was to verify whether a correlation between mucins phenotype and Lauren's classification subsists. 40 gastric adenocarcinomas, subdivided, according to Laurèn's classification, into 27 intestinal-type, 10 diffuse-type and 3 unclassified cases, were examined for MUC1 and MUC2 immunohistochemical expression. Intestinal-type carcinomas displayed a MUC1-positive staining in 23/27 cases and a MUC2-positive immunoreaction in 10/27 cases. Diffuse-type carcinomas expressed MUC1 in 3/10 and MUC2 in 8/10 cases, respectively. According to the mucins expression pattern, three phenotypes were identified: the gastric phenotype (MUC1+/MUC2-); the gastro-intestinal phenotype (MUC1+/MUC2+) and the intestinal phenotype (MUC1-/MUC2+). The gastric phenotype was significantly higherin intestinal-type adenocarcinomas, whereas cases showing an intestinal phenotype were significantly more frequent in diffuse-type adenocarcinomas. These findings provide evidence for a lack of correlation between Lauren's classification and MUC1 and MUC2 phenotypes. In particular, the term intestinal-type tumour as referred to gland-forming gastric cancer does not seem to reflect an immunohistochemical phenotype.

Caveolin-1 immuno-expression in human fetal tissues during mid and late gestation.

Caveolin-1 (Cav-1) is the main protein in caveolae, and serves as a scaffolding protein onto which many classes of signalling molecules are assembled. Through interaction with proto-oncogene products, Cav-1 may suppress cell proliferation; or when phosphorylated, may also stimulate cell growth. The aim of this study was to determine Cav-1 expression in human fetal tissues, tissues composed of cells undergoing growth and differentiation processes which require a nurturing environment provided by transmembrane vesicular transport. By using immunohistochemistry, Cav-1 was detected in several fetal tissues during mid- and late gestation (from 14 to 39 weeks). The protein was present in adipocytes, endothelial cells, smooth muscle fibers and in a number of sites with a pattern of distribution similar to that of the adult. Intriguingly, a positive immunoreaction for Cav-1 was also noticed in tissues, such as the urothelium, which normally do not express this protein in adulthood. This unexpected pattern of Cav-1 in human fetus may predict novel roles for Cav-1 during fetal development.

Utilization of guidelines for the management of hypertension in cardiovascular risk scoring of renal patients.

BACKGROUND: Recent guidelines for the management of hypertension by the European Societies of Hypertension and Cardiology (ESH-ESC), consider, besides normal and normal high blood pressure, also early renal failure as a significant factor scoring the individual cardiovascular (CV) risk in each patient. Considering that the nephrologists have not yet adopted a similar system to score CV risk in renal failure, we believed reasonable to evaluate whether the ESH-ESC guidelines were applicable to renal patients and to what extent useful to estimate the CV risk in chronic renal disease. PATIENTS AND METHODS: According to the above-mentioned guidelines, CV risk score was evaluated in 386 ambulatory patients (212 M/174 F; aged 53 +/- 15 years) with the following clinical diagnosis: hypertension (n=48), lithiasis (n=49), chronic renal failure (n=182), transplantation (n=61) and dialysis (n=46). RESULTS: We obtained a "no score" group and five progressive risk classes graded from 1 to 5. Infact thirthyfour cases were not scored because of "optimal" blood pressure control, whilst the remaining 352 averaged a score of 3.9 +/- 1.1 ("high" CV risk condition). In these, all the scores were present and the distribution of cases evidenced a prevailing of score 4 and 5 in chronic renal failure (19 and 52% of the cases, respectively) and in transplantation (26% and 39%), but not in hypertension and lithiasis. In dialysis, only score 4 and 5 (35% and 59% respectively) occurred, while 4 cases (6%) were not scored due to "optimal" blood pressure values. Target organ damage, acquired clinical conditions, modifiable and non-modifiable risk factors had all a positive correlation with the risk score. CONCLUSIONS: Our study suggests that ESH-ESC guidelines for the management of hypertension can be used to obtain a global CV risk score also in chronic kidney diseases, with the exception of dialysis. In chronic renal failure, the risk of underestimating the real incidence of future CV events might be overcome, at least partially, by the possibility of highlighting in individual patients the concomitance of risk factors requiring a very early preventive and aggressive therapy.

[Comparison among ecography, scintigraphy and surgery in the localization of parathyroid glands in uremic patients undergoing parathyroidectomy]. / Confronto tra ecografia, scintigrafia e chirurgia nella localiz- zazione delle ghiandole paratiroidi nei pazienti uremici in dialisi sottoposti a paratiroidectomia.

BACKGROUND: Sensitivity and specificity of the most widely employed techniques of parathyroid glands localization, namely echography and scintigraphy, are mostly obtained with short-term follow-up data and do not underline the existence of a methodological problem. As a matter of fact, both methods identify only pathological glands, with no "normal" results; therefore "true negatives" cannot be obtained. Aim of our study was to compare, by means of a statistically appropriate approach, the results of echography, scintigraphy and surgery with the data obtained after a mid term follow-up period, enabling us to discover all parathyroid glands. METHODS: Twenty six consecutive dialysis patients (14M/12F; age 50+/-12 years) underwent echography and scintigraphy immediately before a total parathyroidectomy with autotransplantation and were followed-up for 6 months to recognize all the existing glands (PTH levels and scintigraphy). RESULTS: Total identified glands were: 73 by scintigraphy, 86 by echography, 99 by surgery and 103 by follow-up data. The concordance indexes (K0) between the number of glands effectively present in the individual patient (follow-up data) and those identified with each method were rather low with scintigraphy (0.071) and echography (0.218), and acceptable (0.578) with surgery. The number of patients correctly classified was: 9/26 (34,6%) with scintigraphy, 13/26 (50%) with echography and 22/26 (85%) with surgery. Finally, the number of wrongly identified glands (from zero to three) in each patient was similar with scintigraphy (65,4%) and echography (50%) and significantly better with surgery (15,6%; p<0.01). CONCLUSIONS: The most reliable technique to identify parathyroid glands in uremic subjects is surgery, nonetheless a meticulous clinical follow-up is necessary to recognize all of them.

Mutual information-based feature selection for low-cost BCIs based on motor imagery.

In the present study a feature selection algorithm based on mutual information (MI) was applied to electro-encephalographic (EEG) data acquired during three different motor imagery tasks from two dataset: Dataset I from BCI Competition IV including full scalp recordings from four subjects, and new data recorded from three subjects using the popular low-cost Emotiv EPOC EEG headset. The aim was to evaluate optimal channels and band-power (BP) features for motor imagery tasks discrimination, in order to assess the feasibility of a portable low-cost motor imagery based Brain-Computer Interface (BCI) system. The minimal sub set of features most relevant to task description and less redundant to each other was determined, and the corresponding classification accuracy was assessed offline employing linear support vector machine (SVM) in a 10-fold cross validation scheme. The analysis was performed: (a) on the original full Dataset I from BCI competition IV, (b) on a restricted channels set from Dataset I corresponding to available Emotiv EPOC electrodes locations, and (c) on data recorded with the EPOC system. Results from (a) showed that an offline classification accuracy above 80% can be reached using only 5 features. Limiting the analysis to EPOC channels caused a decrease of classification accuracy, although it still remained above chance level, both for data from (b) and (c). A top accuracy of 70% was achieved using 2 optimal features. These results encourage further research towards the development of portable low cost motor imagery-based BCI systems.

Immunolocalization of lactoferrin in surgically resected pigmented skin lesions.

Lactoferrin (Lf) expression was determined immunohistochemically in 57 formalin-fixed paraffin-embedded bioptic samples obtained from an equal number of patients treated by surgery to remove pigmented skin lesions (nevi = 23; melanoma = 12; vulgaris and seborrhoeic warts = 12; basal cell carcinoma = 10); in addition, 10 specimens of normal skin were studied as control. On 3 mm thick sections, depigmentation and antigen retrieval procedures were performed. The Lf immunoreactivity was revealed by a rabbit anti-human Lf. Quantification of Lf immunoreactivity was performed using an intensity-distribution (ID) score. Melanocytic cells, regardless of their benign or malignant nature, were consistently stained, with no significant differences in the Lf ID-score between melanomas or nevi. A different intensity of Lf immunoreactivity was encountered in superficial portions of warts, exclusively inside squamous epithelial cells arranged in sheets or whorls of keratin. On the contrary, basal cell carcinomas were always unstained, while a slight Lf positivity was found in focal keratinized areas present in two tumours showing baso-squamous differentiation. The Lf immunoreactivity was localized in the cytoplasm and only occasionally in the nucleus. The biological meaning of Lf in these cases of human skin specimens remains unexplained, although it cannot be ruled out that Lf might be involved in the defense system against tumours, or alternatively, may be used by cells requiring iron availability for their turnover. Moreover, the immunohistochemical expression of Lf in melanocytic lesions might be also related to a Lf-melanin interaction. Finally, the involvement of Lf in skin squamous non-neoplastic elements could be related to its role as one of the molecules modulating an unspecific inflammatory or anti-oxidant response.

Immunoexpression of CD30 and CD30 ligand in deciduas from spontaneous abortions.

In the present study, using immunohistochemistry, we studied the expression of CD30 and CD30-L in 35 deciduas obtained from women following elective abortion during normal physiological gestation and in 60 deciduas obtained from women after spontaneous abortion with or without signs of inflammation. The main difference was noticed in the first trimester of gestation in which was found a decrease in CD30/CD30-L-positive decidual glandular and stromal cells in a greater number of cases of spontaneous abortions with respect to cases of physiological pregnancies (70% vs 50%, p<0.05). In addition, deciduas from spontaneous abortions with inflammation and without inflammation reacted similarly. The reduced expression of CD30 and CD30-L and their cellular pattern detected in the deciduas from spontaneous abortions suggest that the CD30/CD30-L system is crucial for preventing abortions in the first trimester. Furthermore, the distinctive expression of CD30/CD30-L in deciduas from physiological pregnancies may indicate that the CD30/CD30-L system exerts its main role in the first trimester.

Response to STI571 in chronic myelomonocytic leukemia with platelet derived growth factor beta receptor involvement: a new case report.

Based on its ability to inhibit the tyrosine kinase activity of ABL, as well as the c-kit and the Platelet Derived Growth Factor Receptor tyrosine kinases, the spectrum of diseases that may respond to STI571 is increasing. A recently recognized subgroup of myeloproliferative disorders/myelodysplastic syndromes (MPD/MDS) has a t(5;12)(q33;p13) with the activation of the gene for PDGFBR which encodes a receptor tyrosine kinase. Here, we present the case of a patient, with MPD/MDS, and eosinophilia, carrying a translocation t(5;12)(q33;p13) who achieved a complete remission following treatment with STI571, 400 mg daily. At the time of writing he still remains in complete remission with an excellent performance status. There is clearly a need for further studies of STI 571in MPD/MDS with chromosomal translocations involving PDGFBR to confirm this promising initial result.

Iron binding proteins in gallbladder carcinomas. An immunocytochemical investigation.

By immunohistochemistry, the presence of major iron-binding proteins (lactoferrin, transferrin, ferritin) has been investigated in adenocarcinomas (27 cases), adenosquamous carcinoma (1 case), undifferentiated sarcomatoid carcinoma (1 case) and mucinous adenocarcinomas (3 cases) of the gallbladder 10 samples of chronic lithyasic cholecystitis, 4 adenomyomas and 6 tubulo-villous adenomas have also been studied. In a variable share of adenocarcinomas, a positive immunoreactivity for iron-binding antisera was encountered in the cytoplasm, while tubulo-villous adenomas, adenomyomas and the normal epithelium of the gallbladder were generally unreactive. In carcinomatous lesions, the staining intensity was variable between different cases or individual tumour cells. The production of these iron-binding proteins in the gallbladder carcinoma in itself could be related to a greater availability of iron for metabolic processes in the neoplastic cell; alternatively, the cytoplasmic localization of these substances in carcinomatous elements may be a consequence of a defective or impaired function of iron-binding receptors with a modified degree of transmembranous iron transfer.

Lectin histochemistry of human meningiomas.

The lectins Peanut agglutinin (PNA), Canavalia ensiformis (Con A), Ulex europaeus-1 (UEA-1), Dolichos biflorus (DBA), Triticum vulgaris (WGA) were studied in a series of 36 meningiomas (16 meningotheliomatous-including 3 recurrences, 7 transitional, 4 angiomatous, 2 "hemangiopericytic", 3 papillary-including 1 recurrence, 4 anaplastic-including 3 recurrences. PNA binds to all cases of meningotheliomatous, transitional, papillary and anaplastic meningiomas (including recurrent cases) but the staining is more intense in tumor cells of anaplastic and papillary type. A semiquantitative study showed differences of PNA-reactivity in the different subtypes of meningiomas. In meningotheliomatous meningiomas PNA-positivity was encountered in numerous neoplastic cells (50%), whereas papillary and anaplastic subtypes expressed strong cytoplasmic staining of few tumor cells (< 5%). Con A shows the same pattern of reactivity described for PNA, but more weakly. Our results suggest that PNA is a marker of differentiation in meningiomas rather than malignant transformation and can have prognostic relevance.

Iron-binding proteins in human colorectal adenomas and carcinomas: an immunocytochemical investigation.

By immunocytochemistry, the presence of major iron-binding proteins (lactoferrin, transferrin and ferritin) was investigated in tubular adenomas (12 cases), villous adenomas (7 cases), carcinomas of the large bowel and rectum (39 cases) and lymph nodes involved in carcinomas (8 cases); 5 samples of colonic inflammatory pseudopolyps were also studied. Dysplastic areas of tubular and villous adenomas as well as adenocarcinomas and colloid carcinomas showed a variable cytoplasmic immunoreactivity for all antisera, although no staining was noted in some cases; tubular adenomas without dysplasia and colonic inflammatory pseudopolyps were always unstained. Metastatic elements present in lymph nodes maintained the immunohistochemical staining for iron-binding proteins. An autoctone production of lactoferrin, transferrin and ferritin by tumour cells may be hypothesized in relation to the increased requirement of iron for the turnover of rapidly dividing cells.

The use of microwave irradiation for immunohistochemistry: a new methodological proposal.

We developed a rapid immunohistochemical method using a microwave oven in formalin-fixed, paraffin-embedded sections from normal and pathological tissues. The strongest immunoreactivity was obtained for actin, Ca 125, CEA, pan-cytokeratin, chromogranin A, EMA, GFAP, thyroglobulin, kappa and lambda chains. In control tissues, processed with conventional immunocytochemical procedure, the reactivity was found to be qualitatively and quantitatively similar. Dako EPOS kits were also assayed with good staining intensity, shortening the original technique to 16 min. Our microwave immunohistochemical method is simple, rapid and it may be recommended for use in routine laboratories.