Occupational exposure to anaesthetic gases and high-frequency audiometry.

OBJECTIVES: Occupational exposure to anaestethic gases has been suggested to induce auditory damages. The aim of this study is to investigate high-frequency audiometric responses in subjects exposed to anaesthetic gases, in order to highlight the possible effects on auditory system. METHODS: The study was performed on a sample of 30 medical specialists of Messina University Anaesthesia and Intensive care. We have used tonal audiometry as well as high-frequency one. We have compared the responses with those obtained in a similar control group not exposed to anaesthetic gases. Results were compared statistically. RESULTS: Results show a strong correlation (p = 0.000) between left and right ear responses to all the audiometric tests. The exposed and the control group run though the standard audiometry analysis plays different audiometric responses up only to higher frequencies (2000 HZ p = 0.009 and 4000 Hz p = 0.04); in high-frequency audiometry, as all other frequencies, the attention is drew to the fact that the sample groups distinguish themselves in a significantly statistic way (10,000 Hz p = 0.025, 12,000 Hz p = 0.008, 14,000 Hz p = 0.026, 16,000 Hz p = 0.08). The highest values are the ones related to exposed subjects both in standard (2000 Hz p = 0.01, 4000 Hz p = 0.02) and in high-frequency audiometry (10,000 Hz p = 0.011, 12,000 Hz p = 0.004, 14,000 Hz p = 0.012, 16,000 Hz p = 0.004). CONCLUSION: Results, even if preliminary and referred to a low-range sample, show an involvement of the anatomic structure responsible for the perception of high-frequency audiometric responses in subjects exposed to anaesthetic gases.

[Mobbing: between personality traits and organizational-managerial characteristics of the occupational environment]. / Mobbing: tra struttura di personalità e caratteristiche organizzativo-- gestionali dell'ambiente lavorativo.

UNLABELLED: INTRODUCTION. The relationship between stressful events in the workplace and their effect on health is the subject of numerous studies where the phenomenon of"Mobbing" has become of increasing interest in Social Psychiatry and Occupational Medicine. The aim of this study is to evaluate the relationship between mobbing, occupational stress and personality structure in a group of persons who consulted the "Work Adaptation Disorders Centre" at the Institute of Occupational Medicine between December 2008 and June 2010 for mobbing-related issues. METHODS: Referring to Leymann Inventory of Psychological Terrorization (LIPT), H. Ege, Occupational Stress Indicator (OSI), Minnesota Multiphasic Personality Inventory 2 (MMPI-2), it has been possible to assess situations of harassment, the sources and the effects of work stress, as well as personality traits in the study group. RESULTS: The results showed that high levels of occupational stress and inadequate coping strategies can lead to depressive, hysterical and paranoid manifestations. CONCLUSIONS: Although the relationship between mobbing, occupational stress and personality traits still remains controversial, there is an association between perception of adverse behaviour and mental health, regardless of the subject's ability to cope with stressful life events. The data seem to confirm that the prevention of bullying must be implemented by the work organization and by handling interpersonal conflicts in the work context.

Lymph node micrometastasis and survival of patients with Stage I (Dukes' A) colorectal carcinoma.

OBJECTIVE: Although patients with Stage I colorectal cancer show an excellent prognosis, a few of them die of metastatic disease. In this subgroup of individuals, the search of occult metastasis might reveal that early dissemination of tumor cells could be the cause of cancer progression. MATERIAL AND METHODS: Through a Cancer Registry, we selected all patients with Stage I disease who died of metastatic tumor; a total of 32 patients were identified and in 25 of them paraffin-embedded material was available. The group was matched to 70 Stage I patients with favorable prognosis (controls). In cases and controls resected lymph nodes were cut, and micrometastases were searched using pan-cytokeratin antibodies. RESULTS: Micrometastases were detected in 18 of 25 (72%) Stage I patients who died of the disease, while they were almost absent among controls (1 of 70, p < 0.001 by χ(2) test). Vascular invasion and tumor budding were more frequent among Stage I patients with an unfavorable prognosis than in controls. By regression analyses, micrometastases (HR 12.3, CI 4.8-32) and vascular invasion (HR 3.5, CI 1.4-8.5) maintained an independent association with prognosis (cancer-specific survival). CONCLUSION: Micrometastasis in the lymph nodes can be revealed in the majority of patients with early colorectal cancer who die of tumor progression, while they appear extremely rare in Stage I individuals with good prognosis. The selection of patients through histology (vascular invasion) and search of occult metastatic cells might represent a way to identify individuals who might benefit from adjuvant chemotherapy.

Lactoferrin in human tumours: immunohistochemical investigations during more than 25 years.

Lactoferrin (LF) is an iron-binding glycoprotein of the transferrin family, today known to have multifunctional physiological activities. In humans, under normal conditions, LF has been found in blood, mucosal secretions, gastrointestinal fluids, urine and mostly in milk and colostrum. The first pioneering immunohistochemical report about LF distribution in human tissues dated in 1978; successively, many studies have been performed to analyze the LF immunohistochemical pattern in different normal and neoplastic tissues. In this review, we present data from literature concerning the evidence of LF in tumors together with those by us obtained during more than 25 years; the immunohistochemical applications to human neoplastic tissues have been done to investigate the LF pathogenetic role as well as its activity in cancer. After a systematic analysis of LF immunoreactivity in different human districts, a possible explanation for its presence and function has been modulated for each site or tissue, according to experimental evidences obtained either by in vivo as well as by in vitro studies.

Fluorescent in situ hybridization as a screening test for HER2 amplification in G2 and G3 breast cancers of lobular and ductal histotype and metastases.

The aim of the present study was to evaluate the effectiveness of fluorescence in situ hybridisation (FISH), as a screening test, in moderately- (G2) or poorly- (G3) differentiated breast cancers of the ductal (IDC) and lobular (ILC) histotypes and distant metastases. HER2 FISH was performed on 486 G2 and 477 G3 both of IDC and ILC histotypes and in 241 metastases. A significant difference in the HER2 amplification was observed between G2 (14.8%) and G3 (31.9%), with no difference according to the histotype. However, the rate of amplification increased to 36% in the G2/hormone receptor-negative cases as compared to 10.6% in the G2/receptor-positive cases (p<0.0001). HER2 was amplified in 17% of metastases with some differences depending on the location. These data suggest that the HER2 FISH analysis may be an effective screening test in breast cancer metastases and G3 tumors, irrespective of the hormone receptor status or presence of lymphovascular invasion.

Acne inversa complicated by squamous cell carcinoma in association with diffuse malignant peritoneal mesothelioma arising in the absence of predisposing factors: a case report.

Diffuse malignant peritoneal mesothelioma (DMPM) is a relatively rare neoplasm. Risk factors associated with its development include asbestos exposure, chronic irritation or inflammation of the peritoneum, abdominal radiotherapy, familial Mediterranean fever and simian virus 40. A familial segregation of this neoplasia has been reported in small villages of the Cappadocian region of Turkey, and it has been postulated that hereditary factors may predispose to mesothelioma, even with exposure to small amounts of asbestos. We report a case of DMPM, which apparently occurred in the absence of predisposing factors in a patient with a clinical history characterized by recurrent pre-sacral acne inversa of long duration. The association of this chronic inflammatory disease with DMPM has never been reported. The genetic locus for acne inversa has recently been identified within the 1p21.1-1q25.3 chromosomal region. Interestingly, frequent losses in chromosomal region 1p.21-22 have been found in mesothelioma as well. It is thus tempting to speculate that genetic mutations involving chromosome 1p.21-22 may account for the development of both diseases.

Expression of p53/HGF/c-met/STAT3 signal in fetuses with neural tube defects.

Neural tube defects (NTD) are morphogenetic alterations due to a defective closure of neural tube. Hepatocyte growth factor (HGF)/c-met system plays a role in morphogenesis of nervous system, lung, and kidney. HGF/c-met morphogenetic effects are mediated by signal transducers and activators of transcription (STAT)3 and both HGF and c-met genes are regulated from p53. The aim of our study was to analyze mRNA and protein expressions of p53, HGF, c-met, and STAT3 in fetuses with NTD. By reverse transcriptase-polymerase chain reaction and immunohistochemistry, we analyzed neural tissues from four NTD fetuses and the corresponding non-malformed lungs, kidneys and placentas. We found a reduced mRNA expression of HGF/c-met/STAT3 pathway, in the malformed nervous systems and placentas. The reduced expression of this pathway correlated with the absence of p53 in all these samples. On the contrary, detectable expression levels of p53, HGF, c-met, and STAT3 were observed in non-malformed lungs and kidneys obtained from the same fetuses. Comparable results were obtained by immunohistochemistry, with the exception of p53, which was undetected in all fetal tissues. In conclusion, in NTD fetuses, both the defective neural tube tissue and the placenta have a reduction in all components of the p53/HGF/c-met/STAT3 cascade. This raises the possibility of using the suppression of these genes for early diagnosis of NTD especially on chorionic villus sampling.

Immunoexpression of lactoferrin in human sporadic renal cell carcinomas.

By immunohistochemistry, lactoferrin (Lf) expression was retrospectively investigated in 40 formalin-fixed paraffin-embedded kidney samples, obtained at surgery from an equal number of patients. Histologically, 28 cases were clear cell carcinomas (CCC), 7 papillary carcinomas (PC) and 5 chromophobe carcinomas (CC). Ten specimens of unaffected renal parenchyma were utilized as tissue control. On 4-microm thick sections, the Lf immunoreactivity was revealed either by a rabbit polyclonal or mouse monoclonal anti-human Lf antisera; the quantification of Lf immunoreactivity was performed using an intensity-distribution (ID) score. A positive immunoreaction by both anti-Lf antibodies was found in 62.5% (25/40) of RCC, mainly evident and diffuse by monoclonal antiserum. The immunoreactivity was observed in the cytoplasmic boundary of neoplastic cells in CCC and PC, while in CC Lf showed a diffuse granular cytoplasmic localization. Moreover, significant differences in Lf ID score were found among CCC and non-CCC variants (P<0.00001), the former showed a lower score; no relationships between immunohistochemical data and the sex or age of patients, grade of RCC, stage of the disease or degree of terminal anemia were encountered. Normal unaffected tubular structures were positive for Lf; glomeruli were unstained. The reduced Lf immunoexpression in some CCC may be because of the down-regulation of Lf gene due to the frequent deletion of 3p regions reported in this RCC variant.

Clinico-pathological significance of cell-type-specific loss of heterozygosity on chromosome 7q21: analysis of 318 microdissected thyroid lesions.

A careful pathological examination often reveals the presence of different lesions at various stages of tumor progression and invasion, even in those thyroid glands presenting with solitary nodules. Each thyroid lesion is composed of many different cell types, reflecting the marked heterogeneity of normal thyroid tissue. Among the different chromosome regions altered in thyroid tumors, 7q21 appears to be specifically involved in malignant tumors, especially of the follicular type. This study was conducted to analyze the loss of heterozygosity (LOH) pattern at 7q21 in pure populations of cells from each single lesion harbored in surgically removed thyroid glands, and to evaluate its clinical significance. One hundred and forty-two thyroid glands were examined, all showing, as a common trait, a goitrous appearance associated with one single lesion in 114 cases and with more than one in the remaining 28 cases. A total number of 318 lesions was analyzed, consisting of 142 goiters (TG), 48 hyperplasias (TH), 80 adenomas (TA) and 48 carcinomas (TC). Five different types of cells were isolated by laser capture microdissection from each lesion. DNA was analyzed by PCR and polyacrylamide gel electrophoresis in search of LOH affecting five microsatellite markers, D7S660, D7S630, D7S492, D7S657, and D7S689. We detected LOH at 7q21 not only in thyroid malignant tumors but also in benign lesions. Allelic loss occurred exclusively in dark nucleus and eosinophilic cytoplasm cells, commonly observed in the follicular type of lesions. In these types of lesions allelic loss frequency increases along with neoplastic transformation (9% in TG, 41% in TH, 68% in TA and 100% in TC), and is directly correlated with thyroid gland volume as well as with the presence of multiple lesions. The highest LOH rate was observed for D7S492, indicating that the recurrent region of deletion was localized at the corresponding genetic locus at 7q21.2, in the same position where the common fragile site FRA7E was previously mapped. LOH at this locus represents an early event in the development of follicular TC and is associated with intense growth of thyroid glands.

Clinicopathological characteristics, hormone receptor status and matrix metallo-proteinase-9 (MMP-9) immunohistochemical expression in spinal meningiomas.

Meningiomas involving the spinal meninges show a reduced tendency to recur compared to those of the intracranial compartment. Nonetheless, due to the few reports with a significant number of patients, their biological characteristics largely remain to be investigated. With the aim of clarifying the biology of these tumors, we examined in the present paper the clinicopathological features, the estrogen receptor (ER) and progesterone receptor (PR) status, as well as the Ki-67 labeling index (LI) and matrix metallo-proteinase-9 (MMP-9) expression of 58 spinal meningiomas. Ki-67 LI ranged between 1% and 5% (median: 1%); no expression of ER was found in all the cases, whereas PR immunoexpression was found in 86% of the tumors. High MMP-9 expression was encountered in 46% of meningiomas, and it was significantly correlated with the percentage of PR expression. The recurrence rate was 1.7%. The only recurred case showed high MMP-9 expression, absence of PR and low Ki-67 LI. Our findings confirm that spinal meningiomas are indolent tumors with low growth fraction and recurrence rate. In these neoplasms, high MMP-9 expression seems to be associated with the development of recurrences only in the absence of PR expression. Thus, the evaluation of both MMP-9 and PR expression might be of use in the identification of spinal meningiomas at higher risk of relapse.

Diagnostic value of neutrophil gelatinase-associated lipocalin (NGAL) immunoexpression in follicular-patterned lesions of the thyroid gland.

Neutrophil gelatinase-associated lipocalin (NGAL) is a protein which participates in iron trafficking and which is involved in cancerogenesis and cancer progression. Since its over-expression has been documented in thyroid malignancies in comparison to thyroid normal gland, in the present study, we aimed to determine whether the evaluation of NGAL immunoexpression may be of help in the differential diagnosis of follicular-patterned thyroid lesions. Our additional aim was to test the possible interference of endogenous biotin on the immunohistochemical findings. Thus, all the immunohistochemical procedures, carried out with labeled streptavidin biotin method, were doubly performed, with or without the preliminary inhibition of endogenous biotin. No NGAL staining was found in the normal thyroid gland nor in the nodular colloid goiters or in Hashimoto's thyroiditis. NGAL expression appeared to be significantly more frequent in the malignant tumors in comparison to benign ones (P < 0.000001). Even more, NGAL expression appeared to be specific (specificity 93%) for carcinoma and represented a sensitive method (sensitivity 84%), with high negative (88%) and positive (94%) predictive values, as well as high diagnostic accuracy (88%), in the identification of follicular-patterned thyroid malignant tumors. The specificity, positive predictive value and diagnostic accuracy lowered when biotin was not preliminary inhibited, due to the presence of false positives among benign Hürthle cell tumors. In conclusion, the immunohistochemical detection of NGAL may be helpful in the differential diagnosis between malignant and benign follicular-patterned lesions of the thyroid. The use of biotin free system or the preliminary biotin inhibition is warranted for the detection of NGAL in thyroid samples, especially when dealing with Hürthle cell tumors.

Expression of brachyury in hemangioblastoma: potential use in differential diagnosis.

Hemangioblastoma (HBL) accounts for up to 2.5% of all intracranial tumors. It may occur as a sporadic entity or as a part of Von Hippel-Lindau syndrome. Patients with Von Hippel-Lindau syndrome are also at an increased risk of developing clear cell renal cell carcinoma (CCRCC). The distinction of HBL from CCRCC metastatic to the central nervous system (CNS) or from other histologic mimics can be challenging at times when based solely on hematoxylin and eosin-stained sections. In the present study we evaluated the potential use of the immunohistochemical evaluation of brachyury protein in the differential diagnosis of these lesions. Archival tissues from 22 HBLs, 16 primary CCRCCs, 8 CCRCCs metastatic to the CNS, and 4 angiomatous and 4 clear cell meningiomas were retrieved from our surgical pathology files and submitted to the immunohistochemical procedures against brachyury. Cases showing nuclear and/or cytoplasmic staining were considered to be positive for brachyury. Positive cytoplasmic staining was evidenced in the stromal cells of 20 of the 22 HBLs. In most cases, >50% of the neoplastic cells were labeled, with strong or moderate intensity of staining. No nuclear or cytoplasmic staining for brachyury was observed in any of the primary renal or metastatic CCRCCs, nor in either of the meningioma types. Thus, brachyury cytoplasmic staining was demonstrated to be highly specific for HBL (specificity, 100%) and represented a sensible (sensitivity, 91%) method, with high positive (100%) and negative (89%) predictive values and high diagnostic accuracy (95%) in the differential diagnosis between HBL and CCRCC metastatic to the CNS or meningioma. On the basis of our findings we propose the use of brachyury as an additional helpful immunohistochemical marker to resolve the differential diagnosis of HBL toward histologic mimics.

Immunohistochemical assessment of lymphovascular invasion in stage I colorectal carcinoma: prognostic relevance and correlation with nodal micrometastases.

Several studies have suggested that the presence of occult nodal metastases (micrometastases) is related to adverse clinical course in stage I colorectal carcinoma. Herein we analyzed the correlation between nodal micrometastases and lymphovascular invasion (LVI) or lymphatic vessel density (LVD) in a series of stage I colorectal carcinomas; the cohort included cases characterized or not characterized by disease progression during the follow-up. In these cases, LVI and LVD were evidenced through the immunohistochemical detection of the specific marker for lymphatic vessels, D2-40. LVI was significantly more frequent in colorectal carcinomas characterized by the presence of micrometastases (P<0.0001), high peritumoral LVD (P<0.0001), and disease progression (P<0.0001). The analysis for progression risk indicated that nodal micrometastases and LVI were significant, negative, independent prognostic parameters associated with shorter disease-free survival of stage I colorectal cancer (P=0.0001; P=0.0242). In conclusion, in this study we demonstrated for the first time that LVI is significantly associated with nodal occult metastases in stage I colorectal carcinoma. In the light of its significant, independent, prognostic value in this neoplasia, the detection of LVI may represent a faster and cheaper tool compared with the time-consuming evaluation of micrometastases to select high-risk patients who may benefit from adjuvant systemic treatment. Furthermore, the assessment of LVI may be applied to establish the likelihood of nodal involvement from carcinomas treated with conservative local excision techniques, which provide no regional nodes for histologic examination.

Neutrophil gelatinase-associated lipocalin (NGAL) and matrix metalloproteinase-9 (MMP-9) prognostic value in stage I colorectal carcinoma.

The expression of neutrophil gelatinase-associated lipocalin (NGAL) has been suggested to behave like a negative prognostic marker in stage I colorectal carcinoma. In the aim of clarifying whether its association with adverse outcome may descend from NGAL's ability to regulate matrix metallo-proteinase-9 (MMP-9), we analyzed the correlation, prognostic value, and association with neo-angiogenesis of NGAL and MMP-9 immunohistochemical expression in a series of stage I colorectal carcinomas. A variable NGAL immunoexpression was demonstrated in 17 of the 48 analyzed cases with a significantly higher frequency of positive cases among patients showing disease progression. NGAL expression was also positively correlated with VEGF expression detected in the same cases. MMP-9 immunostaining was present in the cytoplasm of the neoplastic cells in 30 cases; no significant correlations were evidenced with NGAL expression, as well as with the various clinico-pathological parameters or with progression of the colorectal carcinomas. By contrast, NGAL expression was confirmed as a significant independent negative prognostic marker related to a shorter disease-free survival in stage I colorectal carcinoma. Our preliminary results suggest that the association of NGAL with poor outcome might be independent from MMP-9 regulation, thus highlighting its prognostic value in this neoplasia. If our findings are confirmed in further analyses, NGAL assessment might be used in order to select those patients with a higher progression risk and to submit them to adjuvant therapies useful to prevent adverse outcome.

Neutrophil gelatinase-associated lipocalin: a new prognostic marker in stage I colorectal carcinoma?

TNM stage I colorectal cancer is commonly characterized by a good prognosis, with 5-year survival of around 80% to 90%. Nonetheless, disease progression occurs in a percentage of cases, although the causes of an adverse clinical course still remain to be clarified. In the present study, we analyzed and compared the immunohistochemical expression of neutrophil gelatinase-associated lipocalin, an iron-binding protein, which is involved in colorectal cancer progression, in series a of 29 surgically resected colorectal carcinomas obtained from patients who died of the disease and in a cohort of 22 colorectal cancers from patients alive 5 years after the initial diagnosis. The prognostic value of neutrophil gelatinase-associated lipocalin expression on the overall survival to colorectal cancer was investigated. Variable neutrophil gelatinase-associated lipocalin immunoexpression was demonstrated in 23 of the 51 analyzed cases, with a significantly higher frequency of positive cases among patients who died of the disease. Moreover, neutrophil gelatinase-associated lipocalin expression appeared to be a significant independent negative prognostic marker related to shorter overall survival in stage I colorectal carcinoma. If our findings are confirmed in further analyses, neutrophil gelatinase-associated lipocalin assessment might be used to select patients with a higher risk of progression and to find adjuvant therapies for the prevention of adverse outcomes.

Neutrophil gelatinase-associated lipocalin immunoexpression in renal tumors: correlation with histotype and histological grade.

Neutrophil gelatinase-associated lipocalin (NGAL) is a 25 kDa protein with roles in iron trafficking as well as in carcinogenesis and progression of several human neoplasias. Although the renal proximal tubule represents a major source of NGAL synthesis under various injurious stimuli to the kidney, NGAL expression has been rarely evaluated in renal tumors up to now. In view of this, in the present study we analyzed the expression of this protein in renal tumors of different histotype and grade so as to evaluate whether a role for NGAL might be also proposed in the carcinogenesis of these neoplasms. NGAL immunoexpression was analyzed in 30 surgically resected renal tumors [18 clear cell, 5 papillary and 3 chromophobe renal cell carcinomas (RCCs), 2 urothelial carcinomas and 2 oncocytomas] and in the peritoneal metastasis of a clear cell RCC. A variable NGAL immunoexpression was found in 28/30 cases. High NGAL expression was significantly associated with the papillary and chromphobe histotypes (P=0.016) and with a higher histological grade of clear cell and papillary RCC (P=0.004). Moreover, NGAL expression was retained in the peritoneal metastasis of clear cell RCC. Our findings demonstrate that NGAL is expressed in several histotypes of renal tumors. Its highest expression in the papillary and chromophobe histotypes might be related to a higher need in iron uptake, which could be exploited in anti-cancer therapies with iron chelators against these neoplasias. Further studies are required to investigate the potential diagnostic utility of NGAL in the early diagnosis of metastatic progression of RCC.

Neutrophil gelatinase-associated lipocalin immunoexpression in colorectal carcinoma: A stage-specific prognostic factor?

TNM post-surgical staging is considered to be one of the most powerful prognosticators for colorectal carcinoma. Although patient survival mostly decreases concomitantly to stage increase, in a percentage of cases TNM stage appears only to express the anatomic extent of the neoplasia with no correlation with clinical outcome. Thus, the identification of additional prognostic markers for colorectal cancer is required. Neutrophil gelatinase-associated lipocalin (NGAL) is a 25-kDa protein that appears to play an important role in colorectal cancer progression. In order to evaluate whether NGAL expression may be considered as a predictor of colorectal cancer progression, we analyzed its correlation with clinicopathological characteristics, as well as with patient progression-free survival in a series of surgically resected colorectal carcinomas. A variable NGAL immunoexpression was found in 24 out of the 64 analyzed cases. When only the positive cases were considered, a significant association was found between a high NGAL expression and the presence of distant metastases or high tumor stage. In addition, the presence of NGAL was a significant negative prognostic marker correlated with a shorter progression-free survival in stage I colorectal carcinoma, but not in the remaining TNM stages. If our findings are confirmed in more extensive analyses on stage I colorectal carcinoma, NGAL assessment may be used in order to select those patients with a higher progression risk and to submit them to adjuvant therapies useful to prevent adverse outcome.

Stage I colorectal carcinoma: VEGF immunohistochemical expression, microvessel density, and their correlation with clinical outcome.

Tumor-node-metastasis (TNM) stage I colorectal cancer is commonly characterized by a good prognosis, with 5-year survival around 80-90%; nonetheless, it undergoes disease progression in a percentage of cases, although the causes of adverse clinical course still remain to be elucidated. In the present study, we analyzed and compared the immunohistochemical expression of the pro-angiogenic vascular endothelial growth factor (VEGF) as well as the microvessel density (MVD) in a series of 27 surgically resected colorectal carcinomas obtained from patients deceased because of disease progression and in a cohort of 25 colorectal cancers from patients still alive with no evidence of disease progression 5 years after the initial diagnosis. The prognostic value of VEGF expression and of MVD on the overall survival to colorectal cancer was investigated. A variable VEGF immunoexpression was demonstrated in all the analyzed cases. High VEGF expression was significantly more frequent among patients deceased of the disease. These patients also displayed significantly higher MVD counts in their cancer in comparison to the patients alive after 5 years from surgery. Moreover, both high VEGF expression and MVD appeared as significant negative prognostic markers related to a shorter overall survival to stage I colorectal carcinoma, with VEGF representing an independent variable at multivariate analysis. VEGF assessment might be used in order to select those patients with a higher progression risk and to submit them to adjuvant therapies useful to prevent adverse outcome.

Adiponectin immunohistochemical expression in colorectal cancer and its correlation with histological grade and tumour microvessel density.

AIMS: Adiponectin (ApN) is a 30 kDa adipo-cytokine with anti-angiogenic effects. The expression of its receptors, Adipo-R1 and Adipo-R2, has been reported in colorectal cancer tissue and cell lines, but ApN expression in this neoplasia has not been investigated until now. In the present study, we aimed to analyse ApN expression and its eventual correlations with the clinico-pathological parameters and with the quantity of neo-angiogenesis, as reflected by the microvessel density (MVD), in human sporadic surgically resected colorectal carcinomas. METHODS: A total of 45 formalin-fixed, paraffin-embedded colorectal carcinomas were submitted to the immunohistochemical procedures for ApN and CD105, a specific marker for neo-angiogenesis which was used in the assessment of MVD. RESULTS: ApN expression was evidenced in 12 of 45 colorectal carcinomas, and it was significantly associated with a high histological grade (p = 0.0002) and a low MVD count (p = 0.0471) of the tumours. No ApN immuno-expression was found in the epithelial cells lining the adjacent normal colorectal mucosa. CONCLUSIONS: Our findings suggest an anti-angiogenic role for ApN in colorectal cancer. Nonetheless the significance of the prevalent expression of this cytokine in high-grade colorectal carcinomas needs to be elucidated before considering the use of ApN analogues as novel possible anti-tumour agents.