PubMed Health⌕ Search

Biomedical subjects

Marco Santucci

Publications and source records attributed to Marco Santucci.

At least 19 recordsLinked to original sources
PubMed2006

Expression of p16 in sinonasal malignant melanoma.

The aim of this study was to investigate the expression of p16 in relation with the histopathologic features and the clinical course in patients with sinonasal melanoma. Thirty-seven sinonasal melanomas were immunostained for p16. Seventeen tumours were investigated for loss of the 9p21 region using interphase fluorescence in situ hybridization (FISH). Twenty-seven melanomas (72.9%) showed loss of p16 expression. All cases with spindle or mixed cytology showed loss of p16, whereas this was present in 50% of epithelioid tumours (p=0.01). Loss of p16 expression was more frequently seen in melanomas with alveolar architecture (87.5%) than in tumours with diffuse architecture (68.9%) (p=0.4). There was no correlation between p16 expression and presence of lymph node or distant metastases (p=0.57 and 0.24, respectively). In addition, p16 status did not influence overall survival (p=0.2). The FISH results were in good agreement with immunohistochemistry: 11 tumours out of 17 showed deletion of the 9p21 region and 10 of these showed loss of protein expression. Loss of p16 expression is a frequent event in sinonasal melanoma and it is mainly related to deletion of 9p21 region. At variance from cutaneous melanoma, loss of p16 is not correlated with the prognosis of patients affected by sinonasal melanoma.

Aged↗
PubMed2006

Prognostic factors in primary cutaneous B-cell lymphoma: the Italian Study Group for Cutaneous Lymphomas.

PURPOSE: Primary cutaneous B-cell lymphomas (PCBCLs) are a distinct group of primary cutaneous lymphomas with few and conflicting data on their prognostic factors. PATIENTS AND METHODS: The study group included 467 patients with PCBCL who were referred, treated, and observed in 11 Italian centers (the Italian Study Group for Cutaneous Lymphomas) during a 24-year period (1980 to 2003). All of the patients were reclassified according to the WHO-European Organisation for Research and Treatment of Cancer (EORTC) classification. RESULTS: Follicle center lymphoma (FCL) accounted for 56.7% of occurrences, followed by marginal-zone B-cell lymphoma (MZL; 31.4%); diffuse large B-cell lymphoma (DLBCL), leg type, was reported in 10.9% of patients. Radiotherapy was the first-line treatment in 52.5% of patients and chemotherapy was the first-line treatment in 24.8% of patients. The complete response rate was 91.9% and the relapse rate was 46.7%. The 5- and 10-year overall survival (OS) rates were 94% and 85%, respectively. Compared with FCL/MZL, DLBCL, leg type, was characterized by statistically significant lower complete response rates, higher incidence of multiple cutaneous relapses and extracutaneous spreading, shorter time to progression, and shorter OS rates. The only variable with independent prognostic significance on the OS was the clinicopathologic diagnosis according to the WHO-EORTC classification (DLBCL, leg-type, showed a significantly worse prognosis v FCL and MZL; P < .001), whereas the only variable with independent prognostic significance on disease-free survival was the presence of a single cutaneous lesion (P = .001). CONCLUSION: Our study identifies a possible PCBCL subclassification and the extent of cutaneous involvement as the two most relevant prognostic factors in PCBCL. These data can be considered reasonably as the clinical background for an appropriate management strategy.

Aged↗
PubMed2006

Inducible nitric oxide synthase activity correlates with lymphangiogenesis and vascular endothelial growth factor-C expression in head and neck squamous cell carcinoma.

Nitric oxide (NO) is a diatomic free radical molecule that has been implicated in tumour angiogenesis and progression of head and neck squamous cell carcinoma (HNSCC). However, the mechanism underlying the effect of NO on tumour spread remains largely unknown. Tumour lymphangiogenesis has recently received considerable attention and there is increasing evidence that it is relevant for metastasis to lymph nodes in HNSCC. Here, we study the correlation between inducible NOS synthase (iNOS) activity and lymphangiogenesis in a series of 60 HNSCCs and the possible involvement of the lymphangiogenic factor vascular endothelial growth factor (VEGF)-C. HNSCC presenting with lymph node metastasis had a significantly higher lymphatic vessel density in both the tumour mass and the peritumour area (p = 0.006 and p = 0.001, respectively). Similarly, tumours with lymph node metastasis showed greater lymphatic vessel area than tumours with no lymph node involvement (p = 0.001 for intratumour lymphatics and p < 0.001 for peritumour lymphatics). iNOS activity measured in specimens from the tumour periphery correlated strongly with both lymphatic vessel density and lymphatic vessel area (p = 0.01, rs = 0.45 and p < 0.001, rs = 0.725, respectively). Conversely, these correlations were not observed in specimens from the tumour core. In addition, VEGF-C mRNA expression was significantly elevated in tumours with high iNOS activity (p = 0.008, rs = 0.563), and VEGF-C expression correlated positively with the presence of lymph node metastases (p = 0.03). In vitro, in the A431 human squamous carcinoma cell line, exogenous and endogenous stimulation of the iNOS pathway led to up-regulation of VEGF-C, which was blocked by the NOS inhibitor L-NNA. Taken together, our results indicate that iNOS activity may promote lymphangiogenesis and spread to lymph nodes in HNSCC, with the possible involvement of VEGF-C.

Aged↗
PubMed2006

Evidence for differential expression of Notch receptors and their ligands in melanocytic nevi and cutaneous malignant melanoma.

The Notch signaling has been implicated in the regulation of self-renewal of adult stem cells and differentiation of precursors along a specific cell lineage, in normal embryonic development and organogenesis. There is also evidence that signaling through Notch receptors regulate cell proliferation and cell survival in several types of cancer, with opposing results depending on tissue context. No data are available in the literature concerning modulation of the expression of Notch receptors, and their ligands, in human cutaneous malignant melanoma. Here, we have investigated, for the first time, the expression of Notch-1, Notch-2, Jagged-1, Jagged-2 and Delta-like 1 proteins, by immunohistochemistry, in a series of benign and malignant human melanocytic lesions: five common melanocytic nevi, five 'dysplastic nevi' and 20 melanomas (five in situ, five T1-T2, five T3-T4 and five metastatic melanomas). We found that the expression of Notch-1 and Notch-2, as well as Notch ligands, was upregulated in 'dysplastic nevi' and melanomas as compared with common melanocytic nevi. These results indicate that the activation of Notch may represent an early event in melanocytic tumor growth and upregulation of Notch signaling may sustain tumor progression.

Adult↗
PubMed2005

A kindred with MYH-associated polyposis and pilomatricomas.

MYH-associated polyposis (MAP) is a recently described autosomal recessive form of familial adenomatous polyposis (FAP) associated with susceptibility to colorectal carcinoma (CRC). MAP is caused by biallelic inactivating mutations of the MYH gene, a component of the base excision repair (BER) machinery, whose dysfunction leads to an increase in the rate of G > T transversions following DNA oxidative damage. MAP patients can present with either classic or attenuated polyposis. However, the MAP colonic and extracolonic phenotype has yet to be defined. We report on two siblings, born from consanguineous parents, who were found to be homozygotes for an MYH frameshift mutation. The propositus presented with a low number of colonic lesions and an early-onset CRC. Both siblings had a history of pilomatricomas, benign tumors derived from hair follicles, in childhood. The findings presented provide further evidence of phenotypic variability in MAP, and suggest that multiple pilomatricomas may be a useful cutaneous marker of MAP.

Adenomatous Polyposis Coli↗
PubMed2005

WHO-EORTC classification for cutaneous lymphomas.

Primary cutaneous lymphomas are currently classified by the European Organization for Research and Treatment of Cancer (EORTC) classification or the World Health Organization (WHO) classification, but both systems have shortcomings. In particular, differences in the classification of cutaneous T-cell lymphomas other than mycosis fungoides, Sezary syndrome, and the group of primary cutaneous CD30+ lymphoproliferative disorders and the classification and terminology of different types of cutaneous B-cell lymphomas have resulted in considerable debate and confusion. During recent consensus meetings representatives of both systems reached agreement on a new classification, which is now called the WHO-EORTC classification. In this paper we describe the characteristic features of the different primary cutaneous lymphomas and other hematologic neoplasms frequently presenting in the skin, and discuss differences with the previous classification schemes. In addition, the relative frequency and survival data of 1905 patients with primary cutaneous lymphomas derived from Dutch and Austrian registries for primary cutaneous lymphomas are presented to illustrate the clinical significance of this new classification.

Humans↗
PubMed2005

Expression of protease-activated receptors 1 and 2 in melanocytic nevi and malignant melanoma.

Protease-activated receptors (PARs) are members of the G protein-coupled receptor superfamily that are activated by the proteolytic cleavage of their amino terminal domain. PAR-1 activation by thrombin results in several biologic effects, including platelet adhesion to other cells or extracellular matrix, fibroblast, and endothelial cell growth, whereas PAR-2, activated by trypsin, has mainly a proinflammmatory and angiogenetic role. PAR-1 and PAR-2 modulate cell proliferation in physiopathologic cell invasion processes, suggesting that they may play a role in the setting of cancer growth and metastasis. Here, we have investigated the expression of PAR-1 and PAR-2 proteins by immunohistochemistry in a series of benign and malignant melanocytic lesions: 20 melanocytic lesions (10 common melanocytic nevi and 10 atypical or "dysplastic" melanocytic nevi) and 50 melanomas (10 in situ melanomas, 10 melanomas T1, 10 melanomas T2, 10 melanomas T3 to T4, and 10 metastatic melanomas). PAR-1 was significantly overexpressed in atypical nevi and melanomas in comparison with common melanocytic nevi. PAR-2 was strongly and diffusely expressed by immunohistochemistry in all melanocytic lesions, with no statistically significant differences between nevi and melanomas. Because we found a differential expression in PAR-1 protein, but not in PAR-2, we next investigated the expression of PAR-1 messenger RNA (mRNA) by ribonuclease protection assay in paraffin-embedded tissues using a paraffin block RNA isolation procedure. Similarly to immunohistochemical results, PAR-1 mRNA expression was significantly higher in atypical nevi and melanomas in comparison with common nevi and controls. Overexpression of PAR-1 in atypical nevi and melanomas supports a role for PAR-1 in the initial phases of melanoma development as well as in tumor progression and metastasis. Conversely, the significance of PAR-2 up-regulation in both benign and malignant melanocytic lesions requires further research.

Adult↗
PubMed2005

Defining early mycosis fungoides.

This editorial review summarizes the results of 5 meetings sponsored by the International Society for Cutaneous Lymphoma at which the clinicopathologic and ancillary features of early mycosis fungoides were critically examined. Based on this analysis, an algorithm was developed for the diagnosis of early mycosis fungoides involving a holistic integration of clinical, histopathologic, immunopathologic, and molecular biological characteristics. A novel aspect of this algorithm is that it relies on multiple types of criteria rather than just one, for example, histopathology. Before its finalization, the proposed diagnostic algorithm will require validation and possibly further refinement at multiple centers during the next several years. It is anticipated that a more standardized approach to the diagnosis of early mycosis fungoides will have a beneficial impact on the epidemiology, prognostication, treatment, and analysis of clinical trials pertaining to this most common type of cutaneous lymphoma.

Algorithms↗
PubMed2005

WHO/EORTC classification of cutaneous lymphomas 2005: histological and molecular aspects.

UNLABELLED: The new WHO/EORTC classification for cutaneous lymphomas comprises mature T-cell and natural killer (NK)-cell neoplasms, mature B-cell neoplasms, and immature hematopoietic malignancies. It reflects the unique features of lymphoproliferative diseases of the skin, and at the same time it is as compatible as possible with the concepts underlying the WHO classification for nodal lymphomas and the EORTC classification of cutaneous lymphomas. This article reviews the histological, phenotypical, and molecular genetic features of the various nosological entities included in this new classification. These findings always have to be interpreted in the context of the clinical features and biologic behavior. AIM: To review the histological, phenotypical and molecular genetic features of the various nosological entities of the new WHO/EORTC classification for cutaneous lymphomas. METHODS: Extensive review of the literature cited in Medline and own data of the authors. RESULTS: The WHO/EORTC classification of cutaneous lymphomas comprises mature T-cell and NK-cell neoplasms, mature B-cell neoplasms and immature hematopoietic malignancies. It reflects the unique features of primary cutaneous lymphoproliferative diseases. CONCLUSION: This classification is as much as possible compatible with the concept of the WHO classification for nodal lymphomas and the EORTC classification of cutaneous lymphomas. The histological, phenotypical and molecular genetic features always have to be interpreted in the context of the clinical features and biologic behavior.

Europe↗
PubMed2004

Tumor lymphangiogenesis in head and neck squamous cell carcinoma: a morphometric study with clinical correlations.

BACKGROUND: Tumor metastasis to regional lymph nodes via the lymphatic system represents the first step of dissemination in head and neck squamous cell carcinoma (HNSCC) and serves as a major prognostic indicator for disease progression and as a guide for therapeutic strategies. In the current study, the authors investigated whether tumor lymphangiogenesis may be related to the risk of lymph node metastasis and to clinical outcome in patients with HNSCC. METHODS: Immunostaining for the lymphatic marker D2-40 was used, and lymphangiogenesis was quantified within the tumor and in the peritumoral area in 52 HNSCC specimens using computer-assisted morphometric analysis. RESULTS: Lymphatic vessels were found to be significantly more numerous and larger in the peritumoral area compared with within the tumor, and the number and relative area of intratumoral and peritumoral lymphatics was significantly higher in HNSCC cases with lymph node metastasis. Multivariate analysis demonstrated that high peritumoral lymphangiogenesis (above the median value) was associated with an increased risk of developing lymph node metastasis. No correlation was found between tumor lymphangiogenesis and the disease-free or overall survival in the current series. CONCLUSIONS: The results indicate that peritumoral lymphangiogenesis may be an indicator of the risk of lymph node metastasis in patients with HNSCC.

Aged↗
PubMed2004

Vasculogenic mimicry has no prognostic significance in pT3 and pT4 cutaneous melanoma.

The concept of vasculogenic mimicry has been introduced to define periodic acid-Schiff (PAS)-positive channels and loops lined by tumor cells, instead of endothelium, able to contribute to microcirculation in uveal melanomas. Previous studies have shown that the PAS-positive patterns are associated with a poor prognosis in uveal melanoma. The aim of the current study was to investigate whether vasculogenic mimicry has a prognostic impact in pT3 and pT4 cutaneous melanoma. Fifteen patients with pT3 and pT4 cutaneous melanoma who did not experience progression after 10 years of follow-up and 30 matched controls who underwent progression were selected. Tumor sections were stained with PAS reaction, omitting the nuclear counterstaining. For immunohistochemistry, sections were stained with CD31, CD105 (endoglin), and laminin. Differences in the distribution of the PAS-positive patterns and a series of clinicopathological variables were evaluated by the Pearson chi(2) and Mann-Whitney U tests. We observed PAS-positive linear sheets, arcs, elliptical loops, and networks encircling roundish to oval aggregates of melanoma cells. The overall distribution of the PAS-positive patterns did not match with the blood microvessels' architecture as detected by immunohistochemical analysis. No statistically significant differences in the distribution of PAS-positive patterns were found between cases and controls. The presence of a parallel pattern correlated significantly with thickness (P = 0.04), whereas an inverse correlation was found with vessel area (P = 0.05). In conclusion, our results suggest that there is a mismatch between vasculogenic mimicry and tumor angiogenesis and do not support any prognostic role of vasculogenic mimicry in thick cutaneous melanoma.

Adult↗
PubMed2004

Atypical CD30+ cutaneous lymphoid proliferation in a patient with tuberculosis infection.

We describe the case of a 65-year-old woman affected by a diffuse lymphadenopathy consistent with tuberculous infection who developed a papular eruption on the head and neck region. Histopathologic examination of one papule showed an atypical CD30+ lymphoid infiltrate, which initially was cause of concern for the pathologists but was eventually regarded as reactive in nature. The case reported herein enlarges the spectrum of inflammatory infiltrates in which atypical CD30+ cells may be found. Since the reactive atypical CD30+ cells are morphologically similar to those cells observed in CD30+ lymphoproliferative disorders, including lymphomatoid papulosis, complete clinical history and laboratory findings are necessary to make the final and correct diagnosis. Although the pathogenetic relevance of the presence of CD30+ cells within the cutaneous infiltrate of patients with systemic tuberculosis remains to be determined, our findings support the hypothesis that the cytokine profile associated with tuberculosis may not be strictly TH1-like, and that a TH1-like to TH2-like switch may also occur.

Aged↗
PubMed2004

Primary cutaneous B-cell lymphomas. Current concepts. I.

BACKGROUND: Primary cutaneous B-cell lymphoma (pCBCL) has only recently been recognized as a distinct clinicopathologic entity. This entity represents a wide spectrum of lymphoproliferative disorders that must be separated from non-Hodgkin's B-cell lymphomas secondarily involving the skin and cutaneous B-cell pseudolymphomas. They are defined as B-cell lymphomas originating in the skin, with no evidence of extracutaneous disease at presentation, as assessed by adequate staging procedures. INFORMATION SOURCES: With the advent of improved immunophenotyping and immunogenotyping, increasing numbers of pCBCL cases are being diagnosed. However, there is still confusion regarding the classification, treatment, and prognosis of these patients. The aim of this paper is to provide the clinician with a concise summary of the diagnosis, course, and treatment of pCBCL. Currently, the European Organization for Research and Treatment of Cancer classification is the most adequate classification scheme, identifying the subtypes of pCBCL by clinical behavior and histopathologic findings, and allowing a better management of the patients. STATE OF THE ART: Based on this classification, the most common subtypes of pCBCL are follicular center cell lymphoma and marginal zone B-cell lymphoma, indolent lymphomas with an excellent prognosis (>95% 5-year survival rate in our series). Although local cutaneous recurrences are observed in about 25% of patients, dissemination to internal organs is rare. A less common, specific subtype - the so-called large B-cell lymphoma of the leg(s) - generally has a poorer prognosis, with a 5-year survival rate of approximately 60%. PERSPECTIVES: As a rule, pCBCL is highly responsive to radiation therapy, which should be considered the treatment of choice. Polychemotherapy should be restricted to patients with involvement of several noncontiguous anatomic sites, those refractory or plurirelapsed after radiotherapy, or those with extracutaneous spread.

Adult↗
PubMed2003

Cytotoxic/natural killer cell cutaneous lymphomas. Report of EORTC Cutaneous Lymphoma Task Force Workshop.

BACKGROUND: Cutaneous lymphomas expressing a cytotoxic or natural killer (NK) cell phenotype represent a group of lymphoproliferative disorders for which there is currently much confusion and little consensus regarding the best nomenclature and classification. METHODS: This study analyzes 48 cases of primary cutaneous lymphoma expressing cytotoxic proteins and/or the NK cell marker, CD56. These cases were collected for a workshop of the European Organization for Research and Treatment of Cancer Cutaneous Lymphoma Task Force, to better clarify the clinical, morphologic, and phenotypic features of these uncommon tumors. RESULTS: Several categories with different clinical and pathologic features were delineated: 1) aggressive, CD8+, epidermotropic, cytotoxic T-cell lymphoma; 2) mycosis fungoides, cytotoxic immunophenotype variant; 3) subcutaneous panniculitis-like T-cell lymphoma; 4) NK/T-cell lymphoma, nasal type; 5) CD4+, NK cell lymphoma; 6) blastoid NK cell lymphoma; (7) intravascular NK-like lymphoma; and 8) cytotoxic, peripheral T-cell lymphoma. CONCLUSIONS: Our data show that primary cutaneous cytotoxic/NK cell lymphomas include distinct groups of diseases, clinically, histologically, and biologically. Because the finding of a cytotoxic phenotype often has prognostic significance, the routine use of cytotoxic markers in the diagnosis and classification of cutaneous lymphomas should be expanded.

CD4-Positive T-Lymphocytes↗
PubMed2003

Histopathology and genetics of cutaneous T-cell lymphoma.

There is emerging evidence that genomic and chromosomal instability are features of CTCL, including variants such as MF, Sézary syndrome, and primary cutaneous CD30+ LCAL, and that specific chromosomal abnormalities are common. Additional resolution of specific regions of chromosomal loss and gain are required to define putative genes that may be of fundamental pathogenetic importance in CTCL. Inactivation of well-defined cell cycle and TSG are common as for other types of NHL. The prognostic significance of these abnormalities in CTCL has yet to be determined. The dysregulation of specific transcription factors is of interest, but requires further study. It is hoped that greater understanding of these molecular abnormalities will permit the development of CTCL-specific therapies that alleviate suffering and prolong survival.

Chromosome Aberrations↗
PubMed2003

Cytokine profile and supposed contribution to scarring in cicatricial pemphigoid.

BACKGROUND: The progressive scarring observed in cicatricial pemphigoid (CP) is still partially unexplained but recently the release of soluble fibrogenic factors by inflammatory infiltrating cells has been considered as pathogenically relevant. In the present study we evaluated the expression of mRNA for IL-4, IL-5, TGF-beta1, IFN-gamma in CP in comparison to bullous pemphigoid (BP) patients, investigating the role of cytokine profile as possible cause of the different disease evolution. METHODS: Biopsies from patients with oral (n = 10), preputial (n = 3) and cutaneous (n = 1) CP were studied by in situ hybridisation performing a new amplification system based on biotinyl-tyramide. As control, four patients affected by BP were also examined, together with healthy tissue from two CP and two BP patients, respectively. RESULTS: In CP IL-4 mRNA expression was present in 4 out of 14 cases analysed. IL-5 was detected in 12 CP biopsies. TGF-beta1 and IFN-gamma mRNAs were identified in 9 and 11 CP cases, respectively. In BP, IL-4 hybridisation signal could not be observed in any of the cases. By contrast IL-5, TGF-beta1 and IFN-gamma mRNA analyses were positive in all BP cases. Healthy specimens did not show any expression for IL-4, IL-5 and IFN-gamma, while a poor staining for TGF-beta was found in epithelium and subjunctional areas. CONCLUSIONS: Our results highlight the presence of a mixed cytokine pattern in the cellular infiltrate of both blistering diseases, with a corresponding increase of Th2-like activity in fully developed lesions, irrespective of the different sites involved. In addition, the constant presence of TGF-beta1 mRNA in the different lesional phases of CP, and its overlapping expression in BP suggest that the involvement of additional factors is responsible for the scarring course typical of CP.

Adult↗
PubMed2003

Expression and prognostic significance of matrix metalloproteinases and their tissue inhibitors in primary neuroendocrine carcinoma of the skin.

Matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) have been implicated in the development and progression of many tumors, but data for primary neuroendocrine carcinoma (PNC) of the skin are lacking. The aim of the study was to assess the expression of MMPs and TIMPs in PNC and to evaluate their prognostic significance. Expression of MMP-1, MMP-2, MMP-3, MMP-9, MMP-11, MMP-13, and MMP-14 and TIMP-1, TIMP-2, and TIMP-3 was evaluated by immunohistochemistry on 23 samples of PNC of the skin. The results were matched with clinical features and patient survival. In the 23 specimens of PNC, high (>20% of positive neoplastic cells) MMP-1 expression was found in 13 (56.5%) cases. MMP-2 was evidenced in 12 (52.1%) cases, 8 (34.7%) of which showed high expression in neoplastic cells. MMP-3 was detected in 11 cases (47.8%), with high expression in 9 (39.1%) of them. High MMP-9 expression was observed in 3 (13%) cases, whereas high MMP-14 expression was detected in 11 (47.8%) specimens. Expression of TIMP-1 by neoplastic cells was found in 8 (34.7%) cases, with high expression in 3 cases, whereas high TIMP-3 expression was detected in 21 (91.3%) cases. No immunoreactivity for MMP-11, MMP-13, or TIMP-2 was found. Statistical analysis failed to identify a significant correlation between MMP/TIMP expression and clinical parameters. By univariate analysis, stage >I (P = 0.01), high expression of MMP-1 (P = 0.04) and MMP-3 (P = 0.01) resulted significant negative prognostic factors, whereas by multivariate analysis, stage was the only factor that affected survival (P = 0.02). Our results suggest that MMP-1 and MMP-3 may influence the invasive and metastatic potential of PNCs. It is conceivable that future attempts to specifically block MMP-1 and MMP-3 activity may provide a novel means to inhibit invasiveness and distant spread in selected patients with PNC.

Aged↗