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1.
Toxicol Ind Health ; 31(9): 789-91, 2015 Sep.
Article in English | MEDLINE | ID: mdl-23355493

ABSTRACT

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.


Subject(s)
Anesthetics, Inhalation/administration & dosage , Audiometry/methods , Occupational Exposure/adverse effects , Adult , Auditory Threshold , Environmental Monitoring , Hearing Disorders/chemically induced , Hearing Disorders/diagnosis , Humans , Volatile Organic Compounds/administration & dosage , Volatile Organic Compounds/adverse effects
2.
G Ital Med Lav Ergon ; 34(1 Suppl A): A11-6, 2012.
Article in Italian | MEDLINE | ID: mdl-22888717

ABSTRACT

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.


Subject(s)
Adaptation, Psychological , Bullying , Occupational Health , Personality , Stress, Psychological , Female , Humans , Male , Middle Aged
3.
Pathol Res Pract ; 208(6): 350-5, 2012 Jun 15.
Article in English | MEDLINE | ID: mdl-22494536

ABSTRACT

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.


Subject(s)
Matrix Metalloproteinase 9/metabolism , Meningioma/pathology , Receptors, Estrogen/metabolism , Receptors, Progesterone/metabolism , Spinal Neoplasms/pathology , Adult , Aged , Aged, 80 and over , Biomarkers, Tumor/metabolism , Female , Humans , Ki-67 Antigen/metabolism , Male , Meningioma/metabolism , Meningioma/surgery , Middle Aged , Neoplasm Recurrence, Local , Prognosis , Spinal Neoplasms/metabolism , Spinal Neoplasms/surgery , Spine/pathology , Young Adult
4.
Am J Surg Pathol ; 36(7): 1052-7, 2012 Jul.
Article in English | MEDLINE | ID: mdl-22446946

ABSTRACT

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.


Subject(s)
Biomarkers, Tumor/analysis , Carcinoma, Renal Cell/chemistry , Cerebellar Neoplasms/chemistry , Fetal Proteins/analysis , Hemangioblastoma/chemistry , Kidney Neoplasms/chemistry , Meningeal Neoplasms/chemistry , Meningioma/chemistry , T-Box Domain Proteins/analysis , Adolescent , Adult , Aged , Aged, 80 and over , Carcinoma, Renal Cell/secondary , Cerebellar Neoplasms/pathology , Diagnosis, Differential , Female , Hemangioblastoma/pathology , Humans , Immunohistochemistry , Italy , Kidney Neoplasms/pathology , Male , Meningeal Neoplasms/pathology , Meningioma/pathology , Middle Aged , Predictive Value of Tests , Prognosis , Retrospective Studies , Sensitivity and Specificity , Young Adult
5.
Virchows Arch ; 460(3): 319-25, 2012 Mar.
Article in English | MEDLINE | ID: mdl-22371224

ABSTRACT

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.


Subject(s)
Acute-Phase Proteins/biosynthesis , Carcinoma/diagnosis , Lipocalins/biosynthesis , Proto-Oncogene Proteins/biosynthesis , Thyroid Diseases/diagnosis , Thyroid Neoplasms/diagnosis , Acute-Phase Proteins/analysis , Adult , Aged , Biomarkers, Tumor/analysis , Carcinoma/metabolism , Diagnosis, Differential , Female , Humans , Immunohistochemistry , Lipocalin-2 , Lipocalins/analysis , Male , Middle Aged , Predictive Value of Tests , Proto-Oncogene Proteins/analysis , Sensitivity and Specificity , Thyroid Diseases/metabolism , Thyroid Neoplasms/metabolism , Young Adult
6.
Am J Surg Pathol ; 36(1): 66-72, 2012 Jan.
Article in English | MEDLINE | ID: mdl-21989343

ABSTRACT

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.


Subject(s)
Adenocarcinoma/pathology , Colorectal Neoplasms/pathology , Lymphatic Vessels/pathology , Neoplasm Micrometastasis/pathology , Adenocarcinoma/mortality , Aged , Aged, 80 and over , Antibodies, Monoclonal, Murine-Derived , Colorectal Neoplasms/mortality , Female , Humans , Immunohistochemistry , Kaplan-Meier Estimate , Lymphatic Metastasis , Male , Middle Aged , Neoplasm Invasiveness/pathology , Neoplasm Staging , Prognosis , Proportional Hazards Models
7.
Pathol Res Pract ; 207(8): 479-86, 2011 Aug 15.
Article in English | MEDLINE | ID: mdl-21726963

ABSTRACT

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.


Subject(s)
Acute-Phase Proteins/biosynthesis , Adenocarcinoma/enzymology , Biomarkers, Tumor/metabolism , Colorectal Neoplasms/enzymology , Lipocalins/biosynthesis , Matrix Metalloproteinase 9/biosynthesis , Proto-Oncogene Proteins/biosynthesis , Adenocarcinoma/mortality , Adenocarcinoma/pathology , Aged , Aged, 80 and over , Biomarkers, Tumor/analysis , Colorectal Neoplasms/mortality , Colorectal Neoplasms/pathology , Disease-Free Survival , Female , Humans , Immunohistochemistry , Kaplan-Meier Estimate , Lipocalin-2 , Male , Middle Aged , Neoplasm Staging , Neovascularization, Pathologic/metabolism , Prognosis
8.
Scand J Gastroenterol ; 46(7-8): 881-6, 2011 Jul.
Article in English | MEDLINE | ID: mdl-21492052

ABSTRACT

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.


Subject(s)
Blood Vessels/pathology , Carcinoma/mortality , Carcinoma/pathology , Colorectal Neoplasms/mortality , Colorectal Neoplasms/pathology , Aged , Carcinoma/secondary , Case-Control Studies , Female , Humans , Keratins/metabolism , Lymph Nodes/metabolism , Lymph Nodes/pathology , Lymphatic Metastasis , Male , Middle Aged , Neoplasm Invasiveness , Prognosis , Proportional Hazards Models , Regression Analysis
9.
Biometals ; 24(5): 775-84, 2011 Oct.
Article in English | MEDLINE | ID: mdl-21472415

ABSTRACT

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.


Subject(s)
Lactoferrin/analysis , Neoplasms/metabolism , Humans , Immunohistochemistry , Lactoferrin/metabolism , Tissue Distribution
10.
Hum Pathol ; 42(11): 1720-6, 2011 Nov.
Article in English | MEDLINE | ID: mdl-21420718

ABSTRACT

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.


Subject(s)
Acute-Phase Proteins/metabolism , Colorectal Neoplasms/pathology , Lipocalins/metabolism , Proto-Oncogene Proteins/metabolism , Aged , Aged, 80 and over , Colorectal Neoplasms/metabolism , Colorectal Neoplasms/mortality , Disease Progression , Female , Humans , Lipocalin-2 , Male , Middle Aged , Neoplasm Staging , Prognosis
11.
Oncol Rep ; 24(2): 305-10, 2010 Aug.
Article in English | MEDLINE | ID: mdl-20596614

ABSTRACT

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.


Subject(s)
Acute-Phase Proteins/metabolism , Carcinoma, Renal Cell/metabolism , Carcinoma, Renal Cell/pathology , Kidney Neoplasms/metabolism , Kidney Neoplasms/pathology , Lipocalins/metabolism , Proto-Oncogene Proteins/metabolism , Adult , Aged , Aged, 80 and over , Biomarkers, Tumor/metabolism , Carcinoma, Renal Cell/classification , Carcinoma, Renal Cell/diagnosis , Female , Humans , Immunohistochemistry , Kidney Neoplasms/classification , Kidney Neoplasms/diagnosis , Lipocalin-2 , Male , Middle Aged , Neoplasm Staging/methods , Peritoneal Neoplasms/metabolism , Peritoneal Neoplasms/secondary , Phenotype
12.
Virchows Arch ; 457(1): 11-9, 2010 Jul.
Article in English | MEDLINE | ID: mdl-20532559

ABSTRACT

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.


Subject(s)
Biomarkers, Tumor/analysis , Colorectal Neoplasms/pathology , Neovascularization, Pathologic/pathology , Vascular Endothelial Growth Factor A/biosynthesis , Aged , Aged, 80 and over , Colorectal Neoplasms/metabolism , Colorectal Neoplasms/mortality , Female , Humans , Immunohistochemistry , Kaplan-Meier Estimate , Male , Microvessels/metabolism , Microvessels/pathology , Middle Aged , Neoplasm Staging , Neovascularization, Pathologic/metabolism , Neovascularization, Pathologic/mortality , Prognosis
14.
Oncol Lett ; 1(6): 1089-1096, 2010 Nov.
Article in English | MEDLINE | ID: mdl-22870118

ABSTRACT

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.

15.
Pathology ; 41(6): 533-8, 2009.
Article in English | MEDLINE | ID: mdl-19900101

ABSTRACT

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.


Subject(s)
Adenocarcinoma/metabolism , Adiponectin/metabolism , Colorectal Neoplasms/metabolism , Adenocarcinoma/blood supply , Adult , Aged , Aged, 80 and over , Biomarkers, Tumor/metabolism , Colorectal Neoplasms/blood supply , Female , Fluorescent Antibody Technique, Direct , Humans , Immunoenzyme Techniques , Male , Microvessels/pathology , Middle Aged
16.
Pathol Res Pract ; 205(8): 568-71, 2009.
Article in English | MEDLINE | ID: mdl-19179016

ABSTRACT

Microcystic urothelial carcinoma is a rare variant of transitional cell carcinoma with an indefinite prognostic significance. Herein, we report for the first time the acquisition of microcystic histology in the penile metastasis of a high-grade urothelial carcinoma of the urinary bladder. The patient died of disseminated disease six months later. The immunohistochemical evaluation of mucin expression in the primitive and metastatic tumor suggests that the microcystic histotype may descend from the primitive urothelial carcinoma through a process of dedifferentiation and subsequent redifferentiation. In conclusion, the acquisition of microcystic histology seems to be associated with an aggressive clinical course of the urothelial carcinoma, as already suggested by other authors. Future studies investigating mucin expression in microcystic urothelial carcinoma may help to define the histogenesis of this tumor.


Subject(s)
Carcinoma, Transitional Cell/secondary , Cysts/pathology , Penile Neoplasms/secondary , Urinary Bladder Neoplasms/pathology , Urothelium/pathology , Aged , Biomarkers, Tumor/analysis , Carcinoma, Transitional Cell/chemistry , Carcinoma, Transitional Cell/therapy , Combined Modality Therapy , Cystectomy , Fatal Outcome , Humans , Male , Mucins/analysis , Penile Neoplasms/chemistry , Penile Neoplasms/therapy , Urinary Bladder Neoplasms/chemistry , Urinary Bladder Neoplasms/therapy , Urothelium/chemistry
17.
Arch Pathol Lab Med ; 132(11): 1807-12, 2008 Nov.
Article in English | MEDLINE | ID: mdl-18976020

ABSTRACT

CONTEXT: 5-Lipoxygenase (5-LO) is an arachidonic acid- metabolizing enzyme, which has been demonstrated to exert a role in colorectal cancer tumorigenesis. Its activity in promoting neoangiogenesis in colorectal malignancies has been also recently theorized on the basis of in vitro studies. OBJECTIVE: To investigate whether any correlation existed between 5-LO immunoexpression amount and the quantity of neoangiogenesis, as reflected by microvessel density (MVD) in human sporadic surgically resected colorectal adenocarcinomas. DESIGN: A total of 45 formalin-fixed, paraffin-embedded colorectal adenocarcinomas were submitted to the immunohistochemical procedures for 5-LO and CD105, which represent specific markers for neoangiogenesis and which were used in the assessment of MVD. RESULTS: CD105-positive, intratumoral, newly formed vessels were present in 45 of 45 cases with variable MVD values. A 5-LO-positive immunohistochemical reaction was also found in 45 of 45 cases. A significantly higher MVD was evident in cases displaying a high 5-LO amount in comparison with those characterized by a low 5-LO expression (28.33 vs 19.44 vessels per mm(2); P = .02). In addition, a positive significant correlation emerged between 5-LO immunoexpression amount and the MVD counts (r = 0.2986, P = .04). CONCLUSIONS: Our study demonstrates the existence of a relationship between 5-LO expression and the neoangiogenesis process as reflected by intratumoral MVD in human sporadic colorectal adenocarcinomas, thus suggesting that 5-LO may modulate the formation of blood vessels in these neoplasias.


Subject(s)
Adenocarcinoma/blood supply , Adenocarcinoma/enzymology , Arachidonate 5-Lipoxygenase/metabolism , Colorectal Neoplasms/blood supply , Colorectal Neoplasms/enzymology , Neovascularization, Pathologic/metabolism , Adenocarcinoma/pathology , Adult , Aged , Aged, 80 and over , Antigens, CD/metabolism , Arterioles/pathology , Biomarkers, Tumor/metabolism , Capillaries/pathology , Colorectal Neoplasms/pathology , Endoglin , Female , Humans , Male , Middle Aged , Receptors, Cell Surface/metabolism , Venules/pathology
18.
Oncol Rep ; 19(5): 1271-5, 2008 May.
Article in English | MEDLINE | ID: mdl-18425387

ABSTRACT

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.


Subject(s)
Genes, erbB-2/genetics , In Situ Hybridization, Fluorescence/methods , Receptor, ErbB-2/biosynthesis , Female , Humans , Mass Screening/methods , Medical Oncology/methods , Models, Statistical , Multivariate Analysis , Neoplasm Invasiveness , Neoplasm Metastasis , Neoplasm Staging/methods , Reproducibility of Results , Time Factors
19.
Histol Histopathol ; 23(6): 701-8, 2008 06.
Article in English | MEDLINE | ID: mdl-18366008

ABSTRACT

Endoglin is a 180 KDa glycoprotein mainly expressed on endothelial cells of newly formed vessels. Its expression is increased by the hypoxia inducible factor 1 (HIF-1), a potent stimulator of VEGF expression. The relative hypoxic environment in which foetal lung develops favours HIF-1 dependent gene expression, including the endoglin and VEGF ones. Herein, we analysed endoglin immunoexpression in the human neonatal and foetal lung throughout gestation. Lungs from 18 foetuses (9-41 weeks), 7 preterm and 2 term infants were submitted to the immunohistochemical study. A slight immunostaining was found in some mesenchymal aggregates in the lungs of foetuses at the first trimester of pregnancy. At mid gestation, endoglin was evidenced in peri-tubular mesenchymal stem cells or in peri-canalicular vessels and in the endothelia of peri-bronchial vessels; by contrast, no immunoreaction was observed in case of Down syndrome or in a foetus with cardiac malformations. At late gestation and in preterm infants, endoglin antibody labelled endothelia of the alveolar capillaries and of peri-bronchial vessels. In case of alveolar capillary dysplasia (ACD) or macrosomy associated with maternal diabetes, endoglin expression was restricted to peri-bronchial vessels; no immunoreaction was encountered in foetuses with IUGR (intra-uterine growth restriction) or massive pulmonary haemorrhage. Lungs of term infants both displayed atelectasis; there was no evidence of endoglin immunoexpression in one case, whereby only the endothelia of peri-bronchial vessels were stained in the other. Our study suggests that lung vasculogenesis endures throughout gestation. Absence of endoglin staining in some pathologic conditions may reflect lung vasculogenesis disorders; nonetheless, since each pathologic state is represented by a single case in our cohort, further studies are required to clarify this issue.


Subject(s)
Antigens, CD/metabolism , Fetal Development , Lung/embryology , Receptors, Cell Surface/metabolism , Biomarkers/metabolism , Endoglin , Endothelium, Vascular/metabolism , Endothelium, Vascular/pathology , Fetus , Fluorescent Antibody Technique, Direct , Gestational Age , Humans , Immunoenzyme Techniques , Infant, Newborn , Lung/blood supply , Mesenchymal Stem Cells/cytology , Mesenchymal Stem Cells/metabolism , Pulmonary Atelectasis/metabolism , Pulmonary Atelectasis/pathology
20.
Appl Immunohistochem Mol Morphol ; 16(3): 267-73, 2008 May.
Article in English | MEDLINE | ID: mdl-18301242

ABSTRACT

BACKGROUND: Caveolin-1 (Cav-1) is a 22-kd protein, which exerts essential roles in the regulation of cell proliferation and in transmembrane transport processes. It is mainly expressed in adipocytes, smooth muscle, fibroblasts, and endothelial cells. Its expression in striated muscle fibers is controversial. Indeed, most authors have attributed Cav-1 detection in striated muscle to endothelial cells, adipocytes, and fibroblasts secretion. Nonetheless, recent in vitro studies have shown that Cav-1 is expressed in L6 myoblasts and maintained during the differentiation process. In view of this, and, because only one study has heretofore explored Cav-1 expression in human striated muscle, the aim of the present study was to evaluate and to compare Cav-1 immunohistochemical expression in the human striated muscles of fetus, newborn, and adult. DESIGN: Samples of skeletal muscles of different sites and of myocardium were taken at autopsy from 13 fetuses and 4 newborns and submitted to the immunohistochemical analysis for Cav-1 together with 10 samples of adult skeletal muscle. RESULTS: Myocardial fibers displayed a weak immunoreaction in all samples, from both the newborns and the fetuses, independently of the week of gestation. Conversely, skeletal muscle fibers were only labeled in specimens from fetuses at late gestation and from the newborns, whereas no immunoreaction was evidenced in muscles taken from fetuses at mid-gestation and in the adult samples. CONCLUSIONS: This novel and unexpected pattern of Cav-1 expression in human skeletal muscle suggests a role for Cav-1 in terminal differentiation processes, which need to be clarified by further studies.


Subject(s)
Caveolin 1/biosynthesis , Fetus/metabolism , Muscle, Skeletal/embryology , Muscle, Skeletal/metabolism , Myocardium/metabolism , Adult , Aging/metabolism , Cell Differentiation , Female , Fetus/embryology , Gene Expression Profiling , Gestational Age , Humans , Immunohistochemistry , Infant, Newborn , Male , Pregnancy
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