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M Migaldi

Publications and source records attributed to M Migaldi.

At least 19 recordsLinked to original sources
PubMed2005

PDGFR expression in differential diagnosis between KIT-negative gastrointestinal stromal tumours and other primary soft-tissue tumours of the gastrointestinal tract.

AIMS: To investigate the value of platelet-derived growth factor receptors (PDGFRs) by immunohistochemistry in discriminating KIT-negative gastrointestinal stromal tumours (GISTs) from other soft-tissue neoplasms of the digestive tract. METHODS AND RESULTS: One-hundred and sixty-seven primary gastrointestinal mesenchymal tumours (125 GISTs, 15 intra-abdominal desmoids, 12 leiomyomas, eight leiomyosarcomas, three schwannomas, two solitary fibrous tumours, and one case each of inflammatory pseudotumour and fibroid polyp) were reclassified based on morphology and on the immunohistochemical panel recommended by the National Institutes of Health consensus on GIST. All cases were then tested with antibodies specific for PDGFR alpha and beta. Of 125 GISTs, 117 were KIT-positive (93.6%) and eight KIT-negative (6.4%). All the KIT-positive GISTs were negative for both PDGFRs, while all the eight KIT-negative GISTs expressed PDGFR-alpha, with two of them also coexpressing PDGFR-beta. Among the 42 non-GIST tumours, only a small percentage (26.6%) of desmoids immunostained for PDGFR-alpha, two of them coexpressing PDGFR-beta. CONCLUSIONS: Immunostaining with PDGFR-alpha is a helpful marker in discriminating between KIT-negative GISTs and other gastrointestinal mesenchymal lesions: all KIT-negative GISTs were positive for PDFGR-alpha, while none of the other gastrointestinal mesenchymal tumours analysed, except a small subset of desmoids, was reactive with anti-PDGFRs. These preliminary data demonstrate the suitability of commercially available antibodies to detect immunohistochemically the mutually exclusive expression of KIT and PDGFR-alpha previously reported in GISTs by molecular biological techniques. Since PDGFR exists in the form of a homodimer (alphaalpha, betabeta) or heterodimer (alphabeta) and two of the KIT-negative GISTs coexpressed both PDGFR isoforms, further investigations are required to elucidate the role of PDGFR-beta in GISTs.

Adult↗
PubMed2001

P27Kip1 expression and survival in NO gastric carcinoma.

p27Kip1, a cyclin-dependent kinase inhibitor, is considered to be a tumor suppressor gene. Absent or reduced expression of the p27Kip1 protein has been reported being a negative prognostic marker in primary lung, breast, colon, bladder, and prostate carcinomas. p27Kip1 protein expression was evaluated in a series of 96 gastric carcinomas with no lymph node involvement (NO) to verify any impact on the clinical outcome. The analysis also considered the classic clinico-pathological parameters, such as age, sex, and depth of tumor invasion (pT). The most widely used classification systems for gastric carcinoma were adopted. The expression of p27pKip1 was related neither to the pT category nor to tumor histology. Kaplan-Meier analysis documented a significant impact of an advanced pT category (p < 0.0001) and p27Kip1-reduced expression (p < 0.0002) on survival. Multivariate analysis confirmed that the reduced p27Kip1 protein expression was a strong independent predictor of poor outcome, ranking second to the pT category only (p < 0.006 and p < 0.004 respectively). As reported for other neoplasms, the expression of p27Kip1 appears to be associated with the clinical outcome of gastric carcinoma.

Adenocarcinoma↗
PubMed2000

Loss of p27Kip1 expression is a strong independent prognostic factor of reduced survival in N0 gastric carcinomas.

BACKGROUND: p27KiP1 is a cyclin-dependent kinase inhibitor and is a potential tumor suppressor gene. Reduced expression of p27Kip1 is a powerful negative prognostic marker in primary lung, breast, colon, bladder, and prostate carcinomas. In the current study, the prognostic value of p27Kip1 in gastric cancer was evaluated and compared with other histopathologic parameters and p53 expression. METHODS: p27Kip1 and p53 protein expression were determined by immunohistochemistry in 96 gastric carcinomas. The tumors were from a low incidence population and were selected for the absence of lymph node involvement. RESULTS: Reduced expression of p27KiP1 (< or = 50% positive cells) and nuclear p53 accumulation (> 30% positive cells) were observed in 67 (69.8%) and 9 (9%) tumors, respectively, and were not related to either the pT category or tumor histology. Kaplan-Meier analyses revealed a significant impact on survival by p27Kip1 (P = 0.0001 by log rank test), p53 (P < 0.0001) expression, and the pT category (P < 0.0001). On multivariate analysis, reduced p27Kip1 protein expression was the strongest independent predictor of reduced survival (P = 0.005; relative risk = 3.348) out weighing the pT category (P = 0.010; relative risk = 2.257) and p53 overexpression (P = 0.016; relative risk = 2.618). CONCLUSIONS: These data indicated that immunohistochemical detection of p27Kip1 could help to identify gastric carcinoma patients who are at high risk of death, even in the absence of lymph node involvement, and who might benefit from an adjuvant treatment following surgery.

Adult↗
PubMed2000

p120 expression provides a reliable indication of the rapidity of cell duplication in cancer cells independently of tumour origin.

p120 is a nucleolar protein that has been immunocytochemically detected in rapidly proliferating cells of a variety of human malignancies. In the present study, the relationship between p120 expression and the rapidity of cell proliferation was evaluated in 48 human tumours of different origins. The cell proliferation rate of cancer cells was determined by quantitative analysis of AgNOR proteins. p120 immunostaining and AgNOR protein quantity were measured by image cytometry and a highly significant correlation was found between the two variables, as evaluated by linear regression analysis (r=0.98, p<0.0001). The relationship between p120 expression and the rapidity of cell duplication was also studied in vitro, in six human cancer cell lines derived from different tumour types, characterized by various doubling times (ranging from 20 to 77 h). p120 expression was determined on western blots using specific anti-p120 monoclonal antibodies. Densitometric analysis revealed a highly significant inverse correlation between the integrated optical density values of the chemoluminescence bands at 120 kD and the cell line doubling times (r=-0.93; p=0.007). The same result was obtained in situ by correlating p120 immunostaining of the cytological preparations obtained from the six cancer cell lines with the corresponding doubling time (r=-0.98, p<0.0001). These results indicate that in cancer cells, the quantitative expression of p120 is directly related to the rapidity of cell duplication, independently of the tumour origin.

Antibodies, Monoclonal↗
PubMed2000

Apolipoprotein E polymorphism and breast carcinoma: correlation with cell proliferation indices and clinical outcome.

There is preliminary evidence that polymorphism of apolipoprotein E (apoE, protein; APOE, gene), one of the key regulatory proteins in cholesterol metabolism, influences the pathobiology of carcinoma of the colon, prostate and breast and also primary tumours of the brain. This study was designed to determine whether APOE polymorphism is related to variation in the rate of tumour cell proliferation and clinical outcome in carcinoma of the breast. One hundred and eleven infiltrating ductal carcinomas, for which follow up data were available, were included in the study. Estrogen and progesterone receptor status (ER, PR) cell proliferation index (MIB- 1) and APOE genotypes were determined from paraffin-embedded tissue by standard methods. Positive correlations were found between grade and tumour size, grade and presence of metastasis, grade and MIB-1 expression, as well as between ER and PR. Survival correlated inversely with tumour size and the presence of positive lymph nodes. Both steroid receptors correlated inversely with MIB- 1 expression. PR positive status also correlated inversely with high histological grade and presence of lymph node metastases. APOE allele frequencies resembled those of the general population. No significant associations were found between possession of either APOE epsilon2 or epsilon4 alleles and the parameters investigated. Although there is evidence to suggest that APOE epsilon4 may predispose to the development of carcinoma of the breast our data do not support the hypothesis that APOE genotype influences the rate of tumour cell proliferation or the clinical course.

Adult↗
PubMed2000

Expression of p53 and bcl-2 in clinically localized prostate cancer before and after neo-adjuvant hormonal therapy.

The prognostic significance of p53 and bcl-2 expression in prostate carcinoma is currently under investigation. The aim of the present study was to analyze their expression in diagnostic biopsies and in prostatectomies performed after neo-adjuvant hormonal therapy to investigate their role in hormone resistance. One hundred and six patients with advanced prostate carcinoma were treated for 3 months with LHRH analogues before radical surgery. The expression of p53 and bcl-2 was analyzed by immunohistochemistry in all cases of prostatectomy and in available biopsies obtained before treatment, and was correlated with clinicopathologic parameters and follow-up. A significant increase in p53 expression was found following hormonal therapy, whereas no changes were observed in the expression of bcl-2. The increase in p53 did not correlate with the presence of therapy-induced morphological changes in prostate cancers, but it did correlate significantly with histologic grade and pathologic stage, biochemical progression of the disease, and short overall survival. At multivariate analysis, only grade and stage proved to be independent predictors of shorter survival. There were no correlations between bcl-2 and clinicopathologic variables whether in biopsies or in prostatectomies. The unfavorable clinical course associated with p53-positive carcinomas suggests that neo-adjuvant hormonal therapy may cause the selection of minor p53 mutated clones, rather than the induction of wild-type p53. In any case, the enhanced expression of p53 could label hormone-resistant cancers for further adjuvant therapy.

Aged↗
PubMed2000

Loss of p21Waf1 expression is a strong predictor of reduced survival in primary superficial bladder cancers.

p21Waf1 is a downstream effector of p53 and belongs to the Cip1/Kip1 family of cyclin-dependent kinase inhibitors. Thus, it is a potential tumor suppressor gene and likely plays an important role in tumor development. Moreover, reduced expression of p21Waf1 has been reported to have prognostic value in several human malignancies. In this study, we evaluated the prognostic value of p21Waf1 in bladder cancer compared with other clinicopathological features and with p27Kip1 and p53 expression. A total of 96 superficial (pTa-1) human bladder carcinomas were immunohistochemically stained for p21Waf1 protein expression. Positive p21Waf1 staining (> or =5% positive nuclei) was observed in 68 of the 96 (71%) tumors. p21Waf1 expression was neither associated with tumor stage (P = 0.9) nor with tumor grade (P = 0.18) but was significantly associated with both p53 protein expression (> or =20% positive nuclei; P = 0.007) and with p53 gene mutations (P = 0.017). A significant correlation was also observed between positivity for p21Waf1 and high (>50% positive cells) p27Kip1 expression (P = 0.04). With regard to prognosis, patients whose tumors showed absence of p21Waf1 staining displayed a significantly shorter overall survival (P = 0.01 by log-rank test). However, p21Waf1 expression did not correlate with disease-free survival (P = 0.15 by log-rank test). On a multivariate analysis that also included p53 and p27Kip1 expression, negative p21Waf1 staining was an independent predictor of reduced overall survival (P = 0.004; relative risk, 5.32), stronger than age and tumor stage. These data indicate that expression of p21Waf1 protein strongly correlates with survival and might represent a useful prognostic marker in primary superficial bladder carcinomas.

Adult↗
PubMed1999

Loss of P27Kip1 expression correlates with tumor grade and with reduced disease-free survival in primary superficial bladder cancers.

p27Kip1 is a member of the Cip1/Kip1 family of cyclin-dependent kinase inhibitors and is a potential tumor suppressor gene. We previously reported a deregulated expression of p27Kip1 in a series of human cancer cell lines and in primary breast and colon cancers. Moreover, p27Kip1 has been reported as an important prognostic factor in primary lung, breast, colon, and prostate cancers. In this study, we evaluated the prognostic value of p27Kip1 in a series of 96 superficial (pTa-1) human bladder carcinomas. High (>50% positive cells), moderate (25-50%), and low (<25%) p27Kip1 staining was observed in 39 (41%), 19 (20%), and 38 (39%) of the 96 primary superficial bladder cancers, respectively. No significant association was found between the expression level of p27Kip1 and tumor stage. Decreased p27Kip1 staining correlated with higher tumor grade (P = 0.001). Interestingly, a significant association was observed between increased expression of p27Kip1 and positivity for p53 (>20% positive cells; P < 0.001). A significant correlation was also observed between low expression of p27Kip1 and decreased disease-free survival (P = 0.0003 by log-rank test) and overall survival (P = 0.01 by log-rank test). Furthermore, on multivariate analysis, low p27Kip1 protein expression was an independent predictor of reduced disease-free survival (P = 0.018; relative risk = 1.95) second only to tumor stage. These data indicate that p27Kip1 protein is frequently expressed at low level in poorly differentiated tumors and suggest that this protein might represent a useful prognostic marker for disease recurrence and overall survival in superficial bladder carcinomas.

Adult↗
PubMed1999

The asialoglycoprotein receptor in human hepatocellular carcinomas: its expression on proliferating cells.

The expression of the asialoglycoprotein receptor (ASGP-R) on human hepatocellular carcinoma (HCC) cells might be exploited to reduce the extrahepatic toxicity of DNA synthesis inhibitors by their conjugation with galactosyl-terminating peptides. In the present study we first assessed the frequency of ASGP-R expression in 60 HCCs. Secondly, we investigated whether the receptor was maintained on the plasma membranes of DNA synthesizing cancer cells. Needle biopsies of HCC were evaluated. Diagnosis and grading of HCC were performed on routine haematoxylin and eosin-stained sections according to Edmondson and Steiner (1953). Thirty-five tumours were grade I and II and were classified as well differentiated, while 25 tumours were grade III and IV and were classified as poorly differentiated. Sections from formalin-fixed, paraffin-embedded samples were incubated, after antigen retrieval, with an anti-ASGP-R monoclonal antibody revealed by secondary biotinylated antibody and streptavidin-biotin-peroxidase-diaminobenzidine reaction. A clear immunolabelling of plasma membranes of HCC cells was observed in 28 out of 35 (80%) well differentiated (grade I and II) and in five out of 25 (20%) poorly differentiated (grade III and IV) HCCs. The presence of the ASGP-R on the surface of DNA synthesizing cancer cells was also investigated after in vitro bromodeoxyuridine (BrdU) labelling of HCC samples by immunohistochemical visualization of both the ASGP-R and incorporated BrdU on the same section. The results obtained clearly demonstrated that DNA synthesizing cancer cells expressed the ASGP-R on their surface. The presence of ASGP-R on cell plasma membrane in the majority of differentiated HCCs and its maintenance on proliferating cells encourages studies in order to restrict the action of the inhibitors of DNA synthesis of HCC cells by their conjugation with galactosyl-terminating carriers internalized through this receptor.

Aged↗
PubMed1999

Correlation between high intake of glycyrrhizin and myolysis of the papillary muscles: an experimental in vivo study.

The ingestion of large quantities of glycyrrhizin, whether as a drug or a sweetener, is known, in susceptible subjects, to induce a syndrome similar to hypermineralcorticoidism, with bouts of hypertension, hypokaliaemia and rabdomyolysis, sometimes associated with severe renal failure and hypokaliaemia-induced arrythmias. Glycyrrhizin is also known to isomerize into the glycyrrhetic (or glycyrrhetinic) acids 18alpha- and 18beta-. In previous works, we reported that these metabolites cause bouts of hypertension and reduction in diuresis at low doses in the rat. In particular, the alpha isomer causes significant elimination of the calcium ion in the urine. The present findings confirm that 18alpha-glycyrrhetic acid is more toxic than either glycyrrhizin or the beta isomer. Histopathological study of tissue samples taken from rats treated with the alpha isomer also reveal selective damage to the myocardium with oedema, myolysis, apoptosis and blistering of the sarcoplasm. These effects begin to appear in the course of subchronic treatment, they manifest themselves in acute treatment and correlate closely with the electrocardiographic changes recorded in rats acutely treated with 18alpha-glycyrrhetic acid.

Animals↗
PubMed1999

Detection of human papillomavirus DNA in urinary bladder carcinoma by in situ hybridisation.

AIMS: To investigate the sensitivity of an in situ hybridisation system to detect human papillomavirus (HPV) infection in transitional cell bladder cancer and to evaluate the advantages of analysing multiple biopsies; to examine the correlation between HPV tumour infection detected by in situ hybridisation and the presence of serum anti-HPV antibodies detected by enzyme linked immunosorbent assay (ELISA); and to relate the presence of viral infection to grade, stage, and follow up in cases of bladder cancer. METHODS: The in situ hybridisation technique was used with broad spectrum and type specific (6/11, 16/18, 31/33/35) probes against HPV DNA in formalin fixed, paraffin embedded tissues from 43 cases of bladder cancer. The results were analysed for the presence and type of papillomavirus and correlated with clinicopathological variables. RESULTS: The presence of HPV DNA was identified by the in situ hybridisation technique in 17 of 43 cases of bladder cancer; 12 of these were serum antibody positive and 10 had had multiple biopsies. Fifteen of the cases that were negative for HPV DNA by in situ hybridisation had positive serum serology when tested by ELISA. In 14 cases, the HPV was either types 16/18 or types 31/33/35, both of which carry high oncogenic risk. The stage (p < 0.05) and grade (NS) of the tumour and the outcome on follow up (p < 0.05) were correlated with the presence of HPV infection. CONCLUSIONS: ELISA is not useful in identifying patients with HPV positive bladder cancer, but the use of several probes and multiple biopsies increases the detection rate of HPV in neoplastic tissues. The association between tumour virus infection and high grade/high stage tumours and worse outcome suggests that HPV infection of neoplastic tissue has a negative effect on the behaviour and evolution of transitional cell bladder carcinoma.

Adult↗
PubMed1998

p120 and AgNOR nucleolar protein expression: a comparison with nuclear proliferation markers in oral pathology.

To find a better method for predicting the biological behavior of certain oral cavity lesions, the expression of nucleolar protein p120 and nucleolar organizer region counts (AgNOR) was compared with that of nuclear proliferation markers MIB-1 and PCNA in 10 cases of keratotic epithelial hyperplasia (KEH), 10 cases of epithelial dysplasia (ED), and 15 cases of squamous cell carcinoma (SCC). Significant differences in p120 and AgNOR mean area values and PCNA labeling index (LI) were recorded between KEH and ED, as well as ED and SCC (Student-Neumann-Keuls test). All markers significantly differed between SCC grades I and III. Significant differences were also noted in AgNOR mean area values between grade I and II SCC and in p120 mean area values. MIB-1 and PCNA LI differed significantly when grade II and III SCC were compared (SNK test). There were significant correlations between p120 and AgNOR (Pearson correlation coefficients) and between both of them and the proliferative indexes. AgNOR correlated with tumor grade, stage, and lymph node status (Spearman correlation coefficients), suggesting a prognostic role for that marker.

Analysis of Variance↗
PubMed1998

[AIDS splenomegaly and related iron problems].

Spleens collected from 85 consecutive autopsies of AIDS patients (mean age 37 years) were studied. Splenomegaly, observed in 59 cases (69.4%), does not statistically correlate with life style and blood transfusions. Eleven very large spleens (over 890 g) were associated with opportunistic infections (i.e.: mycobacteria, true fungi and rochalimaea). The histological pattern was characterized by marked lymphoid depletion of the white pulp and--in 67 cases (89.4%)--packing of the pulp cords by macrophages engulfed of brown pigment which was strongly positive to the Perls reaction for ferric iron. The contemporary presence of Perls positive and p24 immunoreactive material was diffusely observed in the cytoplasm of splenic macrophages, also positive to the alkaline tetrazolium reaction. The same was observed in the cytoplasm of monocytes/macrophages of lung and brain (in 5 out of 5 patients with splenomegaly > 600 g, randomly selected). We believe that our findings deal with the formation of a haemoglobin--p24 complex and are in keeping with recent data which suggest the formation of disulphide bonds between viral proteins and haemoglobin.

Acquired Immunodeficiency Syndrome↗
PubMed1997

Immunohistochemical detection of nucleolar protein p120 in paraffin-embedded tissues.

The monoclonal antibody FB-2 recognizes the antigen p120-kDa protein (p120), associated with the nucleolar matrix. p120 has originally been reported as expressed and detectable in malignant and non-neoplastic proliferating cells, but not in most normal resting tissues and benign tumours. In the present study, a reliable immunostaining method was used to detect p120 on formalin-fixed, paraffin wax-embedded tissue, testing it on 148 samples from different neoplastic and non-neoplastic tissues from different organs (breast, colon, lung, prostate, bladder, lymph nodes, skin, tongue and liver). The immunostaining was performed after the application of a specific antigen-unmasking protocol based on six consecutive cycles of microwave oven heating. Under these retrieval conditions, p120 antigen was clearly detectable, not only in hyperplastic and malignant cells, but also in stromal and normal non-proliferating cells of all the tissues evaluated. Our results show that the nucleolar protein p120 can be detected by routine immunohistochemistry in formalin-fixed, paraffin-embedded tissue and is expressed in all nucleated cells under any biological condition.

Antigens, Neoplasm↗
PubMed1996

The changing histopathology of primitive lung cancer.

This study was performed on 1710 lung epithelial malignant tumours, diagnosed in the biennia 1963/1964 (42 cases), 1973/ 1974 (293), 1983/1984 (637) and 1993/1994 (738). It was aimed at evaluating whether, over a time span that long, the distribution of the histopathological patterns could have changed. The neoplasms were classified according to the WHO criteria (1981). From our data, a striking increase becomes apparent for all histotypes. Squamous cell carcinoma holds the leading position both among males and females, even though its rate of increase tends to slow down among males. Analogous trend is observed for all the other histotypes but adenocarcinoma. Among females, the rate of increase continues to accelerate for all histotypes but large cell carcinoma. The male to female ratio is ranging from 2:6 for adenocarcinomas to 12:1 for squamous cell carcinomas. In conclusion, impressive changes seem to have occurred in the frequency of the different lung oncotypes over this time span, especially for adenocarcinoma (increasing trend) and large cell carcinoma (decreasing trend). It also seems worth underlying that the marked increase among females could make lung carcinoma the number one cause of cancer-related deaths in this sex.

Adenocarcinoma↗
PubMed1996

[Bulletin of breast disease: results of the 1990-1994 quinquennium].

All mammary lesions diagnosed at the Institute of Pathological Anatomy of the University of Modena have been systematically filed since 1990 and reported in a bulletin, which is issued twice a year and delivered to health operators. So far, 5.188 cases of breast lesions, comprising 1.999 non-neoplastic pathologies, 1.040 benign tumors, 1.943 primary malignant neoplasms and 206 recurrences, have been filed. During the quinquennium 1990-1994, a progressive numerical reduction in diagnoses of non-neoplastic lesions coupled to an increase of benign tumors has been observed, whereas the number of primary malignant tumors has not changed. In particular, a statistically significant increase in diagnoses of carcinoma-in-situ and of fibrocystic disease associated with moderate-risk lesions (atypical hyperplasias) has been detected, whereas the number of cases of single fibrocystic disease has decreased. This reduction, however, is not significant. A slight increase of breast carcinomas smaller than 1 cm and 2 cm, coupled to a decrease of those exhibiting dimensions between 2 and 5 cm, has been found. The collection and systematic analysis of cases of mammary lesions appears to represent a useful tool to study the incidence of different breast pathologies in the general populations. It can also be viewed as a simple way to test the reliability of diagnostic methods used for selection of surgical cases.

Adult↗
PubMed1995

Argyrophilic nucleolar organizer regions and bromodeoxyuridine and 3[H]-thymidine labelling indices in colorectal cancer.

The count of argyrophilic nucleolar organizer regions (AgNORs) has been proposed as a useful method for evaluating cell replication in human tumours. The current study was undertaken to compare AgNOR values in colorectal cancers with two better established methods for investigating cell proliferation such as bromodeoxyuridine (BrdUrd) and 3[H]-thymidine (3[H]dT) labelling indices (LIs). Because some concern still exists regarding accuracy and reproducibility of AgNOR quantifying methods, we carried out a control study by independently repeating the same measurements (number, area and area per silver-stained NOR particle) in two centres with different operators and computer-assisted image analysers on 40 colorectal carcinomas. AgNOR values recorded in the two centres were strictly correlated (r = 0.75; P < 0.001 for number; r = 0.62, P < 0.01 for area; r = 0.63, P < 0.001 for area per silver-stained NOR particle) and the range of values were almost identical. Then, AgNOR values were compared with BrdUrd and 3[H]dT LIs, respectively obtained by in vivo incorporation and in vitro incubation in the same series of colorectal carcinomas. No correlation was found between AgNOR values and BrdUrd or 3[H]dT LIs. BrdUrd and 3[H]dT LIs were instead reciprocally significantly correlated. No evident correlation was seen between LIs or AgNOR values and clinico-pathological parameters of the tumour. In conclusion, in colorectal neoplasms, AgNOR values did not appear to relate with more direct parameters of cell proliferation. It follows that AgNOR reliability as a biomarker of cell proliferation remains questionable.

Adult↗