Biomedical subjects

G Fontanini

Publications and source records attributed to G Fontanini.

At least 55 records · Page 3Linked to original sources

PubMed1997

Neoangiogenesis and p53 protein in lung cancer: their prognostic role and their relation with vascular endothelial growth factor (VEGF) expression.

Following up-regulation of an angiogenesis inhibitor by the wild-type p53 protein proven recently, we have analysed on the one hand the prognostic impact of microvessel count (MC) and p53 protein overexpression in non-small-cell lung carcinoma (NSCLC) progression and, on the other hand, the inter-relation between the microvascular pattern and the p53 protein expression. Moreover, we assessed the expression of vascular endothelial growth factor (VEGF), one of the pivotal mediators of tumour angiogenesis, in order to investigate its relation to p53 protein expression and MC. Tumours from 73 patients resected for NSCLC between March 1991 and April 1992 (median follow-up 47 months, range 32-51 months) were analysed using an immunohistochemical method. In univariate analysis, MC and p53 accumulation were shown to affect metastatic nodal involvement, recurrence and death significantly. Multiple logistic regression analysis showed an important prognostic influence of MC and nodal status on overall (P = 0.0009; P = 0.01) and disease-free survival (P = 0.0001; P = 0.03). Interestingly, a strong statistical association was observed between p53 nuclear accumulation and MC (P = 0.0003). The same inter-relationship was found in non-squamous histotype (P = 0.002). When we analysed the concomitant influence of MC and p53 expression on overall survival, we were able to confirm a real predominant role of MC in comparison with p53. With regard to VEGF expression, p53-negative and lowly vascularized tumours showed a mean VEGF expression significantly lower than p53-positive and highly vascularized cancers (P = 0.02). These results underline the prognostic impact of MC and p53 protein accumulation in NSCLC and their reciprocal inter-relationship, supporting the hypothesis of a wild-type p53 regulation on the angiogenetic process through a VEGF up-regulation.

Aged↗

PubMed1997

Apoptosis and proliferation in thyroid carcinoma: correlation with bcl-2 and p53 protein expression.

The aim of this study was to determine the apoptotic cell death in 92 thyroid carcinomas of different histotypes (42 papillary, PTC; 12 poorly differentiated, PDC: 21 undifferentiated, UC; and 17 medullary, MC) by terminal deoxynucleotidyl transferase (TdT)-mediated dUTP-digoxigenin nick end labelling (TUNEL). Apoptotic index (Al, evaluated as a percentage of TUNEL-positive cells of neoplastic cells) was calculated in each tumour. The AI was very low in all subtypes of thyroid carcinoma, ranging from a median value of 0.2 in PTC to 1.4 in UC. The proliferative activity was determined by immunohistochemistry using monoclonal antibody, MIB-1. The percentage of proliferating cells was significantly different among the histotypes, increasing with tumour aggressiveness (from the mean value of 3.1 for PTC to 5.6 for PDC and 51.8 for UC). In addition, the ratio between proliferative activity and apoptosis was significantly higher in UC than in the other histotypes. The expression of bcl-2 and p53 protein (important in the modulation of cell death) was correlated (bcl-2, inverse correlation, r2 = 0.1, P = 0.04; p53, direct correlation, r2 = 0.11, P = 0.02) with apoptotic index in PTC.

Antigens, Nuclear↗

PubMed1997

Cytokine production by a new undifferentiated human thyroid carcinoma cell line, FB-1.

A human anaplastic thyroid cancer cell line FB-1, derived from a 68-yr-old woman who underwent surgery for anaplastic thyroid cancer, has been established. The spindlelike cells have been proliferating stably for more than 2 yr. Karyotype analysis shows many abnormalities and many marker chromosomes have been observed. Heterotransplant of FB-1 cells into severe combined immunodeficient mice has resulted in rapidly growing tumors classified as anaplastic carcinomas, although 50% have shown areas with a trabecular pattern. FB-1 cells failed to express messenger RNA for thyroglobulin; TSH-receptor; thyroperoxidase, and placental angiogenic growth factor. Conversely, PAX8 and thyroid transcription factor 1, whose expression is thyroid specific, was kept in an FB-1 cell line at a level comparable with that observed in normal thyroid tissue. In addition, the present cell line expressed high levels of messenger RNA for high-mobility group proteins (Y) and -C. The in vitro study revealed that FB-1 cells are able to produce high levels of interleukin (IL)-8 and medium amount of IL-6, whereas no release of IL-1-alpha, IL-1-beta, and IL-4 was observed. No modulation of cell proliferation and DNA synthesis in FB-1 cells has been observed after the addition of exogenous IL-6.

Aged↗

PubMed1997

67-Kilodalton laminin receptor expression correlates with worse prognostic indicators in non-small cell lung carcinomas.

Tumor samples obtained from 72 patients resected for non-small cell lung cancer were stained immunohistochemically using an immunoperoxidase method and the MLuC5 monoclonal antibody specific for the 67-kDa laminin receptor. Sixty-one of 72 patients (84.7%) displayed a MLuC5-positive reaction, which was usually localized in both the inner surface of the plasmatic membranes and the cytoplasm of neoplastic cells. When we compared the laminin receptor expression with clinicopathological and biological parameters such as histotype, grading, T status, N status, ploidy, proliferative activity, vessel invasion, and p53 protein accumulation, the following results were observed: (a) the mean expression of the receptor was higher in the group of patients with metastatic nodal involvement than in those with uninvolved lymph nodes (P = 0.02); (b) a high Ki-67 score (>13% of positive cells) was observed in tumors with a higher mean value of laminin receptor (P = 0.004); (c) the tumors harboring neoplastic emboli in their vessels showed a higher laminin receptor immunoreactivity (P = 0.02); and (d) a borderline association was found between the high mean value of laminin receptor immunopositivity and p53 accumulation in neoplastic cell nuclei (P = 0.05). Our observations indicate that detection of high tissue levels of 67-kDa laminin receptor is associated with an invasive phenotype in non-small cell lung cancer and may provide further information in the biological characterization of this type of cancer.

Aged↗

PubMed1997

8-Chloro-cyclic AMP inhibits autocrine and angiogenic growth factor production in human colorectal and breast cancer.

8-Chloro-cyclic AMP (8-Cl-cAMP) is a cAMP analogue that specifically down-regulates type I protein kinase A, a signaling protein directly involved in cell proliferation and neoplastic transformation, and that causes growth inhibition in a variety of human cancer cell types. In this report, we have investigated the effects of 8-Cl-cAMP on the expression of several growth factors in human colon (GEO and LS174T) and breast (MDA-MB468) cancer cell lines. 8-Cl-cAMP treatment caused in the three cancer cell lines a significant dose- and time-dependent inhibition in the expression of various endogenous autocrine growth factors, such as transforming growth factor alpha, amphiregulin, and CRIPTO, and of two angiogenic factors, such as vascular endothelial growth factor and basic fibroblast growth factor, at both the mRNA and protein levels. Furthermore, 8-Cl-cAMP treatment markedly inhibited the ability of all three cell lines to invade a basement membrane matrix in a chemoinvasion assay. Finally, 8-Cl-cAMP-induced inhibition of GEO tumor growth in nude mice was accompanied by a significant suppression of transforming growth factor alpha, amphiregulin, CRIPTO, basic fibroblast growth factor, and vascular endothelial growth factor production by the tumor cells, and of neoangiogenesis, as detected by factor VIII staining of host blood cells. These results demonstrate that 8-Cl-cAMP is a novel anticancer drug that inhibits the production of various autocrine and paracrine tumor growth factors that are important in sustaining autonomous local growth and facilitate invasion and metastasis.

8-Bromo Cyclic Adenosine Monophosphate↗

PubMed1997

Vascular endothelial growth factor is associated with neovascularization and influences progression of non-small cell lung carcinoma.

Vascular endothelial growth factor (VEGF) plays a pivotal role in the development of neovascularization in both physiological and pathological processes, e.g., developmental and reproductive angiogenesis, proliferative retinopathies, and cancers. Several solid tumors produce ample amounts of VEGF, which stimulates proliferation and migration of endothelial cells, thereby inducing neovascularization by a paracrine mechanism. Recently, VEGF expression has been shown to significantly affect the prognosis of different kinds of human cancer. Because neoangiogenesis represents an important prognostic indicator of poor prognosis in non-small cell lung cancer (NSCLC), we investigated the influence of VEGF during progression of this type of cancer and its relationship to tumoral neovascularization. VEGF expression was significantly associated with new vessel formation (r = 0.44; P < 0.0001). Moreover, in univariate analysis, VEGF expression significantly affected overall and disease-free survival (P = 0.00003 and P = 0. 0004, respectively). Backward stepwise regression analysis indicated that VEGF expression was an independent prognostic factor in patients with NSCLC. These findings support the hypothesis that VEGF is an important angiogenic factor in primary NSCLC and may help in predicting the outcome of this group of cancers.

Adult↗

PubMed1996

Antitumor activity of combined blockade of epidermal growth factor receptor and protein kinase A.

BACKGROUND: Epidermal growth factor (EGF)-related proteins, such as transforming growth factor-alpha (TGF-alpha), control cancer cell growth through hormonal pathways (i.e., autocrine [hormone acts on cell that produces it] and paracrine [hormone acts on nearby cells] pathways). Overexpression of TGF-alpha and/or its receptor (EGFR) has been detected in human cancers. The blockade of EGFR activation by the use of anti-EGFR monoclonal antibodies (MAbs) has been proposed as a potential anticancer therapy. The type I cyclic adenosine monophosphate (cAMP)-dependent protein kinase (PKAI) is generally overexpressed in human cancer cells and is involved in neoplastic transformation. Inhibition of PKAI by selective cAMP analogues, such as 8-chloro-cAMP (8-CI-cAMP), induces growth inhibition in various human cancer cell lines. PURPOSE: On the basis of our previous observations of a cooperative anti-proliferative effect of anti-EGFR Mab 528 and 8-Cl-cAMP in human cancer cell lines in vitro, we evaluated the anticancer activity in vivo of the combination of an anti-EGFR MAb (MAb C225) and 8-Cl-cAMP. METHODS: Athymic mice were injected subcutaneously with 10(7) human colon carcinoma GEO cells. After 7 days, when established tumor xenografts of 0.30-0.35 cm3 were detectable, 10-15 mice per group were treated intraperitoneally twice weekly with different doses of 8-Cl-cAMP and/or MAb C225. Cancer cell expression of various growth factors was evaluated by immunohistochemical analysis in tumors obtained from control and treated mice. Data were evaluated for statistical significance using the Student's t test and the Mantel-Cox logrank test. All P values represent two-sided tests of statistical significance. RESULTS: A 5-week treatment with low doses of 8-Cl-cAMP (0.5 mg/dose) and MAb C225 (0.25 mg/dose) blocked GEO tumor growth (compared with that in control mice; P < .00001) and suppressed cancer cell production of autocrine growth factors, such as TGF-alpha, amphiregulin, and CRIPTO, and of angiogenic (promotes new blood vessel formation) factors, such as vascular endothelial growth factor and basic fibroblast growth factor, with no signs of toxicity. Control and 8-Cl-cAMP (0.5 mg/dose)-treated mice died within 9-10 weeks after tumor cell injection. In MAb C225 (0.25 mg/dose)-treated mice, GEO tumors resumed a growth rate comparable to that in control animals within 3 weeks following the end of treatment and the mice died between 11 and 20 weeks after tumor cell injection. GEO tumor growth was significantly delayed in the MAb C225 plus 8-Cl-cAMP treatment group (P < .00001) and was accompanied by a prolonged survival of mice (P < .00001) as compared with the control group. CONCLUSIONS: Long-term treatment with a combination of agents that selectively inhibit two intracellular signal-transduction enzymes, such as the PKAI serine-threonine kinase and the EGFR tyrosine kinase, has anticancer activity in vivo, reflected by suppression of tumor proliferation and angiogenesis, with no signs of toxicity. IMPLICATIONS: Since these inhibitors of intracellular mitogenic (growth-stimulating) signaling have a different mechanism(s) of action and do not antagonize the effects of cytotoxic therapy, a combination of anti-EGFR MAb C225 and 8-Cl-cAMP should be investigated as a nontoxic, long-term treatment for cancer patients following chemotherapy.

8-Bromo Cyclic Adenosine Monophosphate↗

PubMed1996

Neoangiogenesis: a putative marker of malignancy in non-small-cell lung cancer (NSCLC) development.

Several studies have documented a relevant prognostic role of microvessel count (MC) in non-small-cell lung carcinomas (NSCLC). However, no evidence has been reported about the involvement of neo-angiogenesis in the development of bronchial cancers. The aim of this study was to analyze microvessel density both in normal and in pathological features of the bronchial tree detected concomitantly with carcinomas. In a group of 34 patients resected for NSCLC, 48 bronchial lesions (hyperplasia, squamous metaplasia, moderate dysplasia and in situ carcinoma) were identified. In addition, 20 samples of normal bronchial epithelium from the same patients were analyzed. A monoclonal antibody was used in order to identify microvessels in the most intense areas of neovascularization from the bronchial specimens. MC was also analyzed in invasive components. An increased number of microvessels was observed from normal to dysplastic epithelium, including in situ carcinoma. Mean MC was significantly lower in normal, hyperplastic and squamous metaplastic epithelium than in dysplastic epithelium and in situ carcinoma. In particular, no differences were observed between normal and hyperplastic/metaplastic components, whereas a statistically significant difference appeared between the latter and dysplastic lesions. Moderate dysplasia and in situ carcinoma showed a number of microvessels in the lamina propria of their mucosa which were not significantly different from the invasive component, whereas hyperplastic/metaplastic lesions presented a much lower number of microvessels than invasive cancer. From these data it appears that normal bronchial epithelium and lesions associated with cancers of the bronchial tree show neovascularization in their stromal component. Hyperplasia and squamous metaplasia, unlike dysplasia and in situ carcinoma, show a low microvessel count, and they cannot represent precursor or incipient changes in the bronchial epithelium before the fully developed in situ stage has also been reached.

Carcinoma in Situ↗

PubMed1996

Prognostic significance of tumoral angiogenesis in completely resected late stage lung carcinoma (stage IIIA-N2). Impact of adjuvant therapies in a subset of patients at high risk of recurrence.

BACKGROUND: Angiogenesis plays a critical role in human tumor growth and metastasis. Microvessel count (MC), as a measure of tumor angiogenesis, has been significantly correlated with metastatic disease in cutaneous, mammary, prostatic, head and neck, and early stage lung carcinoma. METHODS: Ninety-six consecutive patients affected by T1-3N2MO nonsmall cell lung carcinoma (NSCLC), who underwent radical surgery between March 1991 and March 1995 (in many cases followed by adjuvant therapies) were prospectively investigated to assess the prognostic significance of both traditional and new biologic parameters like proliferative activity, blood vessel invasion by tumoral cells, and neovascularization (estimated by the MC). RESULTS: With a median follow-up of 24 months, the projected 3-year survival was 42.1%. Forty-eight of the patients (50%) had already experienced a local (n=14) or systemic (n=34) relapse. The extent of resection (lobectomy vs. pneumonectomy; P=0.0045), the number of mediastinal lymph node levels (single vs. multiple; P=0.014), and the MC (on a X200 field; P=0.015) correlated significantly with metastatic disease. By univariate analysis, significant predictors of survival were: the extent of surgery (P=0.03), adjuvant therapy (P=0.05), and MC (< or = vs. > cut-off; P=0.00076). On multivariate analysis, however, only the MC (P=0.02) retained its level of prognostic significance. CONCLUSIONS: Our results provide evidence that neovascularization, estimated by the MC, can predict metastatic disease and survival in patients with completely resected T1-3N2M0 NSCLC, and may also be useful in patient selection for effective adjuvant treatment.

Actuarial Analysis↗

PubMed1996

Expression of and response to interleukin 6 (IL6) in human mammary tumors.

Multifunctional cytokines play important and only partially defined roles in mammary tumor development and progression. Normal human mammary epithelia] cells (MECs) constitutively produce interleukin (IL) 6, IL8, and a nonsecreted form of tumor necrosis factor. MEC transformation by different oncogenes is frequently associated with alterations of cytokine/growth factor production and responsiveness. This seems particularly true in the case of IL6. Histochemical studies showed that expression of immunoreactive IL6, as compared to normal tissue and to in situ lesions, is significantly reduced in invasive ductal carcinoma. Conversely, the expression of IL6 in invasive lobular carcinoma was enhanced. Expression of TGF-beta1 in mammary neoplasia was in general less intense than that seen in the normal mammary gland. In vitro studies partially supported the in vivo findings: expression of IL6 and TGF-beta1 was significantly down-regulated in cultures derived from both ductal carcinoma and peritumoral tissue. Similarly, responsiveness to IL6 and TGF-beta1 was significantly reduced in neoplastic MECs. The data suggest that alterations of cytokine pathways are present not only in mammary neoplasia, but also in pathologically unaffected breast tissues.

Breast↗

PubMed1996

Defective interleukin six expression and responsiveness in human mammary cells transformed by an adeno 5/SV40 hybrid virus.

Mammary epithelial cells (MECs) were isolated and cultured from mammary glands of healthy women undergoing reduction mammoplasty. Normal MECs were infected with the transforming hybrid virus adeno-5/SV40. Two transformed epithelial cell lines, M1 and M2, were obtained, characterised phenotypically and studied for the production of and the response to cytokines and growth regulators. In both cell lines, expression of the SV40 large T antigen was associated with loss of interleukin 6 (IL-6) production and responsiveness as well as with down-regulation of IL-8 and transforming growth factor (TGF)-alpha production. Both M1 and M2 cell lines were capable of forming colonies in semisolid media, but upon injection into severe combined immunodeficient (SCID) mice only M2 cells were tumorigenic. DNA synthesis in M1 cells was partially inhibited by serum or TNF-alpha and weakly stimulated by hydrocortisone (HC) and IL-8. In contrast, M2 cells were totally unresponsive to a variety of growth regulators. Both lines overexpressed the p53 protein at levels about 20-fold higher than those observed in primary MEC cultures, but no mutations of the p53 gene could be detected. The date confirm the view that the expression in human mammary cells of different oncogenes - including the SV40 T antigen - is frequently associated with alterations of cytokine production and responsiveness.

Adenocarcinoma↗

PubMed1996

bcl-2, p53 and proliferating cell nuclear antigen expression is related to the degree of differentiation in thyroid carcinomas.

Thyroid carcinomas are heterogeneous in terms of histology, clinical presentation, treatment response and prognosis. Since bcl-2 and p53 gene alterations are frequently involved in both lymphoid and epithelial malignancies, we analysed the expression of bcl-2, p53 and proliferating cell nuclear antigen (PCNA) in a group of 134 patients with thyroid neoplasms. The same markers were evaluated in fetal and adult normal thyroids as well as in 40 benign lesions. The study was carried out by immunocytochemistry on archival material using antibodies against bcl-2 and p53 protein on tissue sections of 40 adenomas (As), 20 medullary carcinomas (MCs), 70 well-differentiated carcinomas (WDCs), 20 poorly differentiated carcinomas (PDCs) and 24 undifferentiated carcinomas (UCs). bcl-2 immunoreactivity was detected in 36 out of 40 (90%) As, 20 out of 20 (100%) MCs, 60 out of 70 (85.7%) WDCs, 20 out of 20 (100%) PDCs, and 8 out of 24 (33.3%) of UCs. p53 expression was present in 11.4% of WDCs, 5% of PDCs, 5% of MCs and 62.5% of UCs. By contrast, no p53 immunoreactivity was detected in 40 adenomas and in all the normal thyroid tissues studied. We observed a positive correlation between the expression of p53 and PCNA (r = 0.42; P = 0.035) in a group of UCs, but not in WDCs, PDCs and MCs. Neither p53 nor bcl-2 expression were correlated with clinicopathological parameters, such as age, sex, pTNM and survival. Our results suggest that in tumours of the follicular epithelium p53 and bcl-2 protein abnormalities are associated with more advanced carcinomas and especially with undifferentiated carcinomas, while they are only rarely altered in tumours of the parafollicular C cells.

Aged↗

PubMed1996

Promotion of tumour metastases and induction of angiogenesis by native HIV-1 Tat protein from BK virus/tat transgenic mice.

OBJECTIVE: To characterize the T53 cell line and its clones derived from an adenocarcinoma of BK virus (BKV)/tat transgenic mice and to establish the role of native Tat in tumorigenicity, induction of metastases and angiogenesis. DESIGN AND METHODS: Tat was quantified by flow cytometry and chloramphenicol acetyltransferase (CAT) assays. Tumorigenicity and metastatic ability of cell lines were assayed in nude mice. Production of proteases was evaluated by a plasmin chromogenic assay and gelatinase zymography. The angiogenic effect was studied in vivo with conditioned medium from tumour cell lines. RESULTS: Tat protein was detected in tumour cell lines in amounts from 600-7000 molecules/cell. Conditioned medium from tumour cell lines was able to transactivate an LTR-CAT in HL3T1 cells, indicating release of extracellular Tat. Tumour cell lines, inoculated into nude mice induced angiogenic tumours with remarkable recruitment of host endothelial cells. Metastases were detected in lymph nodes, lungs, kidneys, and heart. Cell lines produced relevant amounts of proteases. Conditioned medium implanted in mice with matrigel induced an angiogenic response, enhanced by addition of heparin. Preincubation with an anti-Tat antibody abolished the angiogenic effect. CONCLUSIONS: Tat from cells from BKV/tat transgenic mice promotes tumorigenesis and formation of metastases and induces angiogenic activity. Angiogenesis occurs at physiological concentrations of Tat lower than 20 ng/ml. The effects of Tat on induction of metastases and angiogenesis appear to be mediated by activation of proteases.

Animals↗

PubMed1996

Tumor uptake and mitotic activity pattern of 5-[125I]iodo-2'- deoxyuridine after intravesical infusion in patients with bladder cancer.

UNLABELLED: In patients with bladder cancer, little is known about diffusion in the tumor mass of 5-iodo-2'-deoxyuridine (IUdR) administered intraluminally, although previous studies based on external scanning have shown promising tumor-targeting properties of IUdR instilled intravesically. This study compared the pattern of IUdR uptake by bladder cancer cells with the actual distribution of mitotic activity, as evaluated by incubation of ex vivo tumor specimens with tritiated thymidine. METHODS: The [125I]IUdR (2-13 MBq) was instilled over 1-3 hr in the bladder of four patients with bladder cancer scheduled for ablative surgery. Twenty-four hours later, surgical samples were assayed for radioactivity and processed for microautoradiography, while fresh tumor specimens were fragmented, incubated with [3H]thymidine and further processed for microautoradiography. The diffusion of labeled IUdR across the bladder wall was evaluated by blood sampling. RESULTS: Tumor incorporation of [125I]IUdR 24 hr after intravesical instillation was 0.002%-0.05% ID/g, while the average tumor-to-normal bladder ratio was about 20. Microautoradiography showed that [125I]IUdR incorporation was confined to tumor cells in the most superficial layers of the bladder, while incubation of the tumor fragments with [3H]thymidine demonstrated the presence of diffuse mitotic activity also in the deeper tumor mass. Diffusion of labeled IUdR in the general circulation was minimal. CONCLUSION: Poor diffusion in the tumor mass makes *IUdR unsuitable for intracavitary therapy of bladder cancer, but the role of such an approach in the postsurgical "sterilization" of cancer remnants floating in the bladder lumen after partial cystectomy should be explored.

Administration, Intravesical↗

PubMed1996

Microvessel count: an indicator of poor outcome in medullary thyroid carcinoma but not in other types of thyroid carcinoma.

The growth of newly formed vessels (neoangiogenesis) represents an important step both in physiologic and pathologic situations. In particular, tumor growth and metastasis require angiogenesis. Microvessel count, which expresses a measure of tumor angiogenesis, has been associated with metastatic spread in cutaneous, mammary, prostatic, head, neck, and pulmonary cancer. In this study, the role of tumor angiogenesis as a prognostic indicator was examined in 157 primary thyroid cancers including 82 well-differentiated carcinomas, 52 medullary carcinomas, and 23 undifferentiated carcinomas. Microvessels were carefully counted by highlighting endothelial cells with anti-CD34 formalin-fixed tumor samples. The mean of microvessel count was 30.7 per field in papillary thyroid carcinomas, 39.4 per field in follicular thyroid carcinomas, 32.7 per field in undifferentiated carcinoma, and 41.8 per field in medullary carcinoma. We found that the number of newly formed vessels was significantly associated with poor prognosis only in medullary carcinoma. All of the dead patients with medullary carcinoma showed a microvessel count higher than 30, which resulted in a high statistical difference compared with alive patients (P = 0.00098). Multiple logistic regression analysis showed microvessel count, together with pTNM (P = 0.026). These results were also confirmed by Kaplan-Meir survival analysis (log-rank test; P = 0.04). By contrast, no differences in the number of microvessels was found between dead and living patients with well-differentiated carcinoma and undifferentiated carcinoma. In conclusion, microvessel count, as quantitation of tumor angiogenesis, plays an important prognostic role in medullary thyroid carcinomas.

Adolescent↗

PubMed1996

Expression of the Mr 67,000 laminin receptor is an adverse prognostic indicator in human thyroid cancer: an immunohistochemical study.

Increased expression of the Mr 67,000 laminin receptor (LR) is a consistent event which appears as cancer cells acquire an invasive and metastatic phenotype. The Mr 67,000 LR is one of the many laminin-binding proteins able to interact with the major glycoprotein of basement membranes, laminin. The recent development of a specific monoclonal antibody directed against the Mr 67,000 LR MLuC5 has allowed us to study large retrospective groups of human cancers with the aim of correlating the Mr 67,000 LR expression to the clinical, pathological, and survival data of the patients. A significant correlation has already been established between the increased expression of Mr 67,000 LR and survival of patients with breast, colon, ovary, lung, and endometrial cancers. In this study, we investigated the possibility that the detection of Mr 67,000 LR in thyroid human cancers could also be of prognostic value. We analyzed the expression of Mr 67,000 LR with immunohistochemistry using MLuC5 antibodies in paraffin sections of 40 benign and 170 malignant thyroid human tumors. We found that Mr 67,000 LR was not usually detectable in normal thyroid tissues adjacent to the lesion. Only 3 of the 40 thyroid adenomas examined (7.5%) presented cells positive for Mr 67,000 LR. For the malignant thyroid tumors examined, we found that 22.3% of papillary thyroid carcinomas, 38% of follicular thyroid carcinomas, 40% of poorly differentiated carcinomas, 25% of medullary carcinomas, and 58.3% of anaplastic carcinomas expressed a high level of Mr 67,000 LR. Although no correlation between the Mr 67,000 LR expression and survival was found in patients with follicular thyroid carcinomas, papillary thyroid carcinomas, anaplastic carcinomas, and medullary carcinomas, there was a significant correlation in primary thyroid cancers. Our data represent the first extensive study of the Mr 67,000 LR expression in human thyroid cancers and strongly suggest that its detection could be of prognostic value in the investigation of primary thyroid cancers.

Adult↗

PubMed1996

Recurrence and death in non-small cell lung carcinomas: a prognostic model using pathological parameters, microvessel count, and gene protein products.

The 5-year survival rate of non-small cell lung carcinoma (NSCLC) has only marginally improved during the past two decades, despite advances in surgery and chemoradiotherapy. Major efforts are currently directed toward biological characterization of these tumors to define biomarkers able to add further prognostic information, thus improving new therapeutic protocols. We analyzed the predictive relevance of the microvessel count (MC), bcl-2 and p53 proteins, proliferative activity, and usual postsurgical parameters on recurrence and overall survival in a series of 70 patients with NSCLC. The expression of biological parameters (p53, bcl-2, proliferative activity, and MC) was detected using immunohistochemistry on paraffin-embedded and frozen sections from the tumors treated with surgical resection alone until relapse. In the univariate analysis, the histotype, tumor status, node status, p53, bcl-2, and MC have been shown to significantly affect progression and death. In the multiple logistic regression analysis, the MC (P < 0.000001), tumor status (P < 0.005), and node status (P < 0.0002) influenced the overall survival while prediction of relapse was strongly revealed by tumor status (P < 0.005), nodal metastatic involvement (P < 0.000001), and the assessment of the vascular count (P < 0.0004). These data have allowed the creation of a multivariate model which may add more information on risk of recurrence and death in patients with NSCLC and can form the basis for future randomized clinical trials.

Aged↗

PubMed1995

Microvessel count predicts metastatic disease and survival in non-small cell lung cancer.

The growth of newly formed vessels, or neoangiogenesis, represents an important step in both physiological and pathological situations: in particular, tumour growth and metastasis require angiogenesis. Microvessel count (MC), which represents a measure of tumour angiogenesis, has been associated with metastatic spread in cutaneous, mammary, prostatic, head and neck, and early-stage lung cancer. In this study, the role of tumour angiogenesis as a prognostic indicator was examined in 253 primary non-small lung cancer (NSCLC) patients. Microvessels were counted by highlighting endothelial cells with anti-Factor VIII monoclonal antibody (Mab) in methacarn-fixed tumour samples. In univariat analysis, MC (P< 0.000001), sex (P=0.0036), histotype (P < 0.014), tumour status (P <0.007), and vessel invasion (P < 0.019) were significantly related to hilar and/or mediastinal nodal involvement. However, in the stepwise logistic regression analysis, MC (P<0.000003) retained the most important influence on nodal metastasis. The overall survival analysis calculated by the Kaplan-Meier method revealed that tumours with high MC ( > 25 vessels/field) were significantly associated with increased death risk (log-rank test P = 0.00067; Cox's test P = 0.00046; Gehan's Wilcoxon test P = 0.00108). In 94 patients, the development of metastatic disease during follow-up was significantly related to MC. Indeed, patients who developed metastasis during follow-up showed a higher MC, either as a dichotomous (P = 0.01) or as a continuous (P = 0.003) variable, than patients who had developed no metastasis at the time of the analysis. Moreover, in the stepwise logistic regression analysis, MC retained the most important influence on distant metastases.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗