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A Franchi

Publications and source records attributed to A Franchi.

At least 19 recordsLinked to original sources
PubMed2000

Prediction of recurrence by microsatellite analysis in head and neck cancer.

We examined the possibility of using microsatellite alterations as markers to detect clonal tumor-derived cell populations in histopathologically negative surgical margins and cervical lymph nodes from head and neck cancer (HNC) patients. We used polymerase chain reaction (PCR)-based microsatellite analysis DNA to analyze primary tumors, paired surgical margins, and cervical lymph nodes from 41 HNC patients. Samples were scored for alterations as defined by the presence of new alleles (shifts) or loss of heterozygosity (LOH) at each of 10 markers. We identified 25 (61%) patients with primary HNC who appeared to have had a complete resection on the basis of the histopathological assessment and who were informative regarding microsatellite alterations in tumor tissue. In 11 of these 25 (44%) cases, PCR analysis of surgical margins showed the same microsatellite alterations as in the primary tumors. In 7 of these 11 patients, the carcinoma recurred locally, as compared with 1 out of 14 patients with negative margins (log rank test, P = 0.0049). Conversely, we were unable to detect clonal neoplastic cells in histopathologically negative lymph nodes examined by molecular analysis. Cox regression analysis showed that molecular positive margins were an independent prognostic factor (P = 0.04) for recurrence. This study demonstrates that microsatellite analysis may be a valuable tool for evaluating the risk of local recurrence.

Aged↗
PubMed2000

The gene encoding the mouse homologue of the human osteoclast-specific 116-kDa V-ATPase subunit bears a deletion in osteosclerotic (oc/oc) mutants.

Osteosclerosis (oc) is an autosomal recessive lethal mutation that impairs bone resorption by osteoclasts, and induces a general increase of bone density in affected mice. Genetic mapping of the oc mutation was used as a backbone in a positional cloning approach in the pericentromeric region of mouse chromosome 19. Perfect cosegregation of the osteopetrotic phenotype with polymorphic markers enabled the construction of a sequence-ready bacterial artificial chromosome (BAC) contig of this region. Genomic sequencing of a 200-kb area revealed the presence of the mouse homologue to the human gene encoding the osteoclast-specific 116-kDa subunit of the vacuolar proton pump. This gene was located recently on human 11q13, a genomic region conserved with proximal mouse chromosome 19. Sequencing of the 5' end of the gene in oc/oc mice showed a 1.6-kb deletion, including the translation start site, which impairs genuine transcription of this subunit. The inactivation of this osteoclast-specific vacuolar proton ATPase subunit could be responsible for the lack of this enzyme in the apical membranes of osteoclast cells in oc/oc mice, thereby preventing the resorption function of these cells, which leads to the osteopetrotic phenotype.

Amino Acid Sequence↗
PubMed2000

Angiokeratoma corporis diffusum (Anderson-Fabry's disease): a case report.

We report on a 14-year-old boy who presented with a 4-year history of acral pains and febrile episodes. On physical examination, numerous small reddish papules were present on his abdomen, located predominantly on the periumbelical region. Renal function was within normal limits. Ophthalmological examination revealed whorled opacities of the cornea (cornea verticillata) and dilated tortuous conjunctival vessels. Histopathological examination of one of the cutaneous papules showed several dilated blood vessels in the superficial dermis surrounded by collarettes of thickened rete ridges, consistent with a diagnosis of angiokeratoma. The electron-microscopic study of a skin specimen demonstrated the presence of dilated lysosomes with deposition of electron-dense bodies, some of which with laminated structure, in endothelial cells and fibroblasts. These findings were regarded as indicative of Fabry's disease. Subsequent biochemical analysis confirmed the presence of a alpha-galactosidase A deficiency in leukocytes. In conclusion, we described the clinical, histopathological and submicroscopic findings of a case of Fabry's disease, in which the combination of electron microscopic and biochemical approaches allowed the correct diagnosis.

Adolescent↗
PubMed2000

Evaluation of a western blot test as a potential screening tool for occupational exposure to Mycobacterium tuberculosis in health care workers.

Health care workers (HCWs) have a higher than average risk for contracting Mycobacterium tuberculosis (MTB) infection and tuberculosis (TB). No markers of MTB-exposure are available, and TB risk assessment is performed by tuberculin screening, identifying individuals with acquired MTB infection. This study evaluated a western blot (WB) anti-M. bovis A60 complex antibody as a MTB-exposure marker. WB reactivity was evaluated on 127 exposed and 28 non-exposed HCWs from four divisions of the Policlinico Hospital of Modena, and 140 non-exposed bacille Calmette-Guérin-vaccinated controls. Excess of occupational TB risk according to the Occupational Safety and Health Administration (OSHA) was calculated in each division. WB-positivity (%) was: (1) significantly higher in exposed HCWs compared with non-exposed (72% vs 25%, P < 0.00001), (2) highly related (r = 0.99) to OSHA risk excess in all divisions, (3) higher than non-exposed in HCWs with short (< 5 years) MTB-exposure (purified protein derivative [PPD], P > 0.18; WB, P < 0.04). PPD-positivity (%) was higher than controls only in HCWs with longer (> 5 years) MTB-exposure. The study suggests that the WB antibody might represent a more sensitive biological marker of MTB contact among exposed HCWs, related to the level of TB risk and detectable earlier than the PPD skin test, thus providing new tools for TB risk assessment in health care facilities.

Adult↗
PubMed2000

Thick cutaneous malignant melanoma: a reappraisal of prognostic factors.

The prognosis of patients with thick (>3 mm) cutaneous malignant melanomas is generally poor; however, some cases survive far longer than expected. Thus tumour thickness cannot serve as the only predictor of disease course in the individual patient. The aims of the current study were to evaluate the clinical outcome of patients with thick (>3 mm) cutaneous melanoma and test the prognostic value of a series of clinicopathological parameters on disease-free and cause-specific survival. We retrospectively evaluated 140 patients with stage I cutaneous melanoma >3 mm in thickness. Disease-free and cause-specific survival rates (Kaplan-Meier method) were compared using the log rank test. A multivariate analysis (Cox proportional hazards model) was used to determine the independent effect of each variable on prognosis. The overall 5-year and 10-year disease-free survival rates were 35.5% and 29.3%, respectively, whereas the overall 5-year and 10-year cause-specific survival rates were 55.3% and 47.7%, respectively. In the univariate analysis, the following factors were found to be significantly associated with the disease-free and cause-specific survival: tumour thickness, mitotic rate/mm2, type of invasive front, ulceration, thickness of the nodular component and predominant cell type. In addition, the presence of vascular invasion was significantly correlated with the risk of metastases but not with survival. In the multivariate analysis (Cox proportional hazards model), only tumour thickness (both as a continuous variable and >7.5 mm), infiltrating invasive front, presence of ulceration and mitotic rate/mm2 (both as a continuous variable and >10 mitoses/mm2) were significant independent predictors of poorer clinical outcome.

Adult↗
PubMed1999

Multiple primary tumors of the upper aerodigestive tract: is there a role for constitutional mutations in the p53 gene?

Head-and-neck cancer (HNC) patients have a high risk of developing second primary tumors of the upper aerodigestive tract, the main cause of death. Although the roles of tobacco and diet in multiple head-and-neck carcinogenesis have been thoroughly investigated, little is known about individual genetic susceptibility factors involved in this process. Genomic instability, reflecting the propensity and the susceptibility of the genome to acquire multiple alterations, could be considered a driving force behind multiple carcinogenesis. Mutation of the p53 tumor-suppressor gene has been proposed to play an important role in this process. Therefore, we evaluated the incidence of inherited p53 germ-line alteration(s) in a population of 24 consecutive HNC patients and their first-degree relatives affected by multiple malignancies as well as the occurrence of p53 somatic acquired mutation(s) in 16 cancers, including first and second primaries from 5 HNCs of the same group. Mutations in exons 4-11 of the p53 gene were investigated using SSCP-PCR analysis and DNA sequencing. Analysis was extended to the peripheral blood and cancer biopsies available from first-degree relatives of cancer-prone families with p53 germ-line mutations. p53 germ-line mutations were identified in the peripheral blood and corresponding cancers of 3 HNC patients who had multiple malignancies. The only missense mutation detected was mapped in exon 6; it is a GTG to GAG substitution with an amino acid change from Val to Glu at codon 197. The remaining 2 p53 germ-line mutations were single-nucleotide substitutions without amino acid change in exon 6 (codon 213, CGA to CGG) and in exon 8 (codon 295, CCT to CCC), respectively. These mutations were found in HNC patients with a family history of cancer. Abnormal expression of wild-type p53 protein in normal and pathological tissues from patients with the same sense single-nucleotide substitutions was detected by immuno-histochemistry.

Adult↗
PubMed1999

Thin cutaneous malignant melanomas (< or =1.5 mm): identification of risk factors indicative of progression.

BACKGROUND: Although thin cutaneous melanomas generally have a favorable prognosis, in some cases they may undergo progression. The current study was undertaken to identify variables that may predict a more aggressive clinical outcome in these patients. In addition to classic clinicopathologic features, the authors tested the prognostic impact of three new morphometric quantitative parameters: 1) tumor thickness plus regression thickness (T+R), 2) percentage of skin thickness infiltrated by tumor cells (T/S ratio), and 3) percentage of skin thickness infiltrated by tumor cells and regression ([T+R]/S ratio). METHODS: The authors retrospectively evaluated 287 patients with invasive cutaneous melanoma < or = 1.5 mm in thickness. Disease free survival rates (Kaplan-Meier method) were compared by using the log rank test. A multivariate analysis (Cox proportional hazards model) was used to determine the independent effect of each variable on progression. Progression was defined as any documented cutaneous local and/or distant metastasis. RESULTS: Thirty-two of the 287 patients (11.1%) underwent disease progression. The overall 5-year and 10-year disease free survival rates were 89.3% and 84.6%, respectively. In the univariate analysis, the following factors were found to be significant predictors of progression: male gender (P = 0.01), acral-lentiginous histotype (P = 0.02), tumor thickness (P = 0.005), T+R (P = 0.001), T/S ratio > or = 50% (P = 0.03), (T+R)/S ratio > or = 50% (P = 0.006), vertical growth phase (P = 0.04), and absence of inflammatory response (P < 0.0001). Conversely, age, site, and Clark's level did not affect the risk of recurrences and/or metastases significantly. In the multivariate analysis, only T+R (P = 0.009) and inflammatory response (P < 0.0001) were found to be independent predictors of progression. Five-year disease free survival rates according to presence versus absence of inflammatory response were 93.4% and 63.8%, respectively (P < 0.0001). CONCLUSIONS: In the current study, peritumoral and intratumoral inflammatory infiltrate and T+R were found to be strong independent predictors of progression in thin cutaneous melanomas.

Adult↗
PubMed1999

Osteonectin expression correlates with clinical outcome in thin cutaneous malignant melanomas.

Osteonectin, also termed BM40 or SPARC (secreted protein, acidic and rich in cysteine) is a multifunctional glycoprotein involved in tissue mineralization, cell-extracellular matrix interactions as well as angiogenesis. It has been suggested that osteonectin may play a key role in the process of tumoral invasion and metastasis in certain malignancies. In this study, we reviewed the clinical records and the histopathologic slides of 188 thin cutaneous malignant melanomas (< or = 0.75 mm). Among them, 12 cases underwent progression and were selected for the study. Osteonectin expression was investigated by immunohistochemistry in these 12 patients and 24 matched controls who did not undergo progression. Osteonectin staining was correlated with clinical outcome and other clinicopathologic parameters. Progression-free and disease-specific survival rates were calculated with the Kaplan-Meier method and their differences were evaluated by the log rank test. Overall, immunoreactivity for osteonectin was found in 23 (63.8%) cases. Eighteen cases (50%) displayed staining in 1% to 50% of neoplastic cells whereas five cases (13.8%) showed a diffuse positivity in more than 50% of the tumor cells. Osteonectin expression was significantly correlated with risk of progression (P = .01), incidence of distant metastases (P = .005) and survival (P = .03). There was a higher incidence of osteonectin-positive tumors in cases that did experience regional lymph node metastases versus those cases that did not, but that difference did not reach statistical significance (P = .06). No significant correlation was found between osteonectin expression and other clinicopathologic features, including age, sex, site, histotype, Clark's level, presence of regression, presence of inflammatory response, and tumor growth phase. Our data showed that osteonectin expression is a predictor of clinical outcome in thin cutaneous melanomas.

Adult↗
PubMed1999

Clinical relevance of the histological classification of sinonasal intestinal-type adenocarcinomas.

To verify the prognostic value of the histological typing of intestinal-type adenocarcinoma (ITAC) of the sinonasal tract, 41 such lesions were separately classified by 2 pathologists both according to the World Health Organization (WHO) criteria for the histological typing of large intestine adenocarcinomas (well, moderately, poorly differentiated adenocarcinomas, and mucinous adenocarcinomas) and to the criteria of Kleinsasser and Schroeder (papillary-tubular cylinder cell type, alveolar-goblet cell type, signet-ring cell type, and transitional type). Using the WHO classification, 7 adenocarcinomas (17.1%) were well differentiated, 15 (36.6%) were moderately differentiated, and 6 (14.6%) were poorly differentiated; 13 cases (31.7%) were classified as mucinous adenocarcinoma. Following the Kleinsasser and Schroeder classification, 28 adenocarcinomas were of the papillary-tubular cylinder cell type (PTCC), 6 tumors (14.6%) were of the alveolar-goblet cell type (AGC), 1 (2.4%) was of the signet-ring cell (SRC) type, and 6 (14.6%) were of the transitional (TR) type. The interrater agreement in subtyping for both histological classifications was 92.6% (kappa, 0.89; P < .001). Kaplan-Meier analysis of cases stratified according to WHO classification showed that patients with mucinous and poorly differentiated adenocarcinomas had a significantly shorter disease-free interval and survival rate than patients with well and moderately differentiated adenocarcinomas (P = .02 and P < .001, respectively; log-rank test). Separate evaluation of survival for patients with AGC and TR adenocarcinomas did not show any statistically significant difference (P = .5). Clinical stage was advanced in most cases (92.6% of patients had T3 or T4 carcinomas) and had no prognostic relevance in the current series, as did treatment and occupational exposure. We conclude that the histological typing of ITACs is highly reproducible and appears to be related to the clinical outcome of the tumors. Adenocarcinomas with a prominent (>50%) mucinous component tend to have a similar clinical behavior, irrespective of their cyto-architectural features and the presence of an associated tubulopapillary component. Therefore, the separation into alveolar-goblet, signet-ring, and transitional forms has no prognostic impact.

Adenocarcinoma↗
PubMed1999

Enumeration of CD34+ hematopoietic progenitor cells for clinical transplantation: comparison of three different methods.

Three different methods for determination of CD34+ cells in G-CSF-mobilized peripheral blood were compared. The methods were: the Milan/Mulhouse protocol, the ISHAGE guidelines for CD34+ cells enumeration and our own protocol. The procedure we have adopted is essentially a Milan/Mulhouse protocol-derived methodology combined with a multiparametric approach using the PAINT-A-GATE software analysis program. The samples were collected from 70 patients affected by acute leukemia, non-Hodgkin's lymphoma, Hodgkin's lymphoma, myeloma and breast cancer who were scheduled to receive autologous PBSC transplantation. PBSC collection was performed following mobilization with subcutaneous G-CSF at 5-10 microg/kg/day. A minimum target of 2 x 10(6)/kg CD34+ cells was considered an acceptable harvest to ensure a safe transplant. On average, three aphereses per patient were performed and a total of 204 apheresis samples were analyzed. Regression analysis of the percentage and absolute number of CD34+ cells, as calculated with each method, achieved an excellent correlation in spite of methodological differences. In fact, both CD34+dim and CD34+CD45- events were included in our gating strategy. In the setting of a triple staining associating CD34, CD38 and CD45, we identified a variable fraction of CD34+CD38+CD45- cells which would be otherwise undetected due to its CD45 negativity. To this end, we used a new technology referred to as laser-scanning cytometry (LSC) which allowed the isolation and morphological identification of CD34+CD45- cells. By comparing CD34+CD45+ and CD34+CD45- cells, we found that they share a common morphology, thus confirming the hypothesis that the latter are to be considered for CD34+ cell calculation. The median number of CD34+ cells/kg, as calculated by the three methods, was: 4.79 x 10(6)/kg (range 1-570) for the Milan/Mulhouse protocol, 3.9 x 10(6)/kg (range 0.8-498) for the ISHAGE one, and 5.17 x 10(6)/kg (range 2-599) for our protocol. The median time to ANC and PLT engraftment was 11 (range 9-24) and 20 (range 10-70) days, respectively. Our protocol achieved the best correlation between CD34+ cells/kg and time to ANC/PLT recovery according to the Spearman's rank test (r = -40 and P < 0. 015 for ANC, r= -46 and P = 0.005 for PLT). We conclude that (1) CD45 does not appear the ideal partner of HPCA-2 for determination of hematopoietic progenitors in mobilized peripheral blood; and (2) for clinical application, a single staining with 8G12 appears simple, reliable and feasible when rigorous procedures for sample preparation and acquisition are followed and an adequate software for multiparametric analysis is available.

Antigens, CD34↗
PubMed1999

The effect of epidermal growth factor on prostaglandin synthesis of oestrogenized rat uterus is mediated by nitric oxide.

We examined the possible relationship between cytokines, nitric oxide and prostaglandins (PGs) in the estrogenized rat uterus. Results indicate that epidermal growth factor (EGF) enhances the synthesis of prostaglandins in estrogenized rat uteri and induces the augmentation of nitric oxide (NO) production in this tissue by stimulating iNOS. While the effect of EGF is abolished by L-NMMA, an NO antagonist, the NS-398, a cyclooxygenase-II (COX-II) inhibitor, prevents the augmentation of prostanoids induced by EGF. These results suggest that there is an interaction among EGF, NO and PGs and that in this interrelationship are involved COX-II and iNOS. This mechanism might be important during implantation and labor.

Animals↗
PubMed1999

Reduced E-cadherin expression correlates with unfavorable prognosis in adenoid cystic carcinoma of salivary glands of the oral cavity.

Reduced expression of E-cadherin (E-cad), a transmembrane glycoprotein, is associated with loss of differentiation, acquisition of an invasive phenotype, and an unfavorable prognosis in carcinomas from several sites. We used immunohistochemistry to study the expression of E-cad in 50 adenoid cystic carcinomas (ACCs) in salivary glands to evaluate correlations with clinicopathologic parameters and patient survival. Absent or low E-cad expression was observed more frequently in solid than in cribriform or tubular carcinomas. E-cad expression also was significantly correlated with histologic grade and the growth pattern. In addition, ACCs showing low or absent E-cad expression were more frequently larger than 4 cm in diameter, and distant metastases developed more frequently. Reduced expression correlated with shorter disease-free intervals and actuarial survival rates. Univariate and multivariate analysis identified tumor stage and E-cad expression as the only 2 parameters predictive of the disease-free interval. E-cad expression and tumor stage, grade, and type of growth were significant prognostic factors for survival in univariate analysis, while tumor stage, type of growth, and E-cad expression were the only significant covariates in multivariate analysis. These findings indicate that the loss of E-cad has an important role in the natural history of ACC, as it is associated with loss of differentiation and development of metastases. We also provide evidence that E-cad expression is an independent indicator of clinical aggressiveness in patients with ACC, together with clinical stage and type of growth at the periphery of the tumor.

Adult↗
PubMed1999

Naevus-associated melanomas: cause or chance?

Controversies exist regarding the true incidence and significance of the histological association between melanocytic naevi and melanomas. The current study was undertaken to determine the incidence of melanocytic naevi histologically associated with melanomas, to compare the clinicopathological profiles of melanomas associated with a naevus (MN+) and melanomas not associated with a naevus (MN-), and to verify the interobserver reliability of classifying the naevus remnants as congenital or acquired. We evaluated 131 patients with invasive melanoma < or = 4 mm in thickness with a Clark's level < V. Histological evidence of an associated melanocytic naevus was found in 27 out of 131 melanoma cases (20.6%). MN+ were significantly more frequent among males compared with MN-(P = 0.002) and were predominantly located on the trunk (P =0.001). No significant differences between MN+ and MN- were found in the distribution of histotype, Clark's level and thickness. Among MN-, the naevus component showed acquired features in 14 cases (51.8%), whereas 12 cases (44.5%) had features of small superficial congenital naevi; in one case (3.7%) a confident distinction between congenital and acquired naevus could not be made. Overall, there was concordance among the three observers in the diagnosis of the type of naevus remnants in 81.4% of cases (kappa = 0.78; P<0.0001). We conclude that, although the majority of cutaneous melanomas arise de novo, in approximately 20% of cases an associated melanocytic naevus is found. Our observation that MN+ and MN- have different clinicopathological profiles suggests that, at least for some cases, a causal relationship between the two lesions may be present. However, when the naevus is histopathologically adjacent to the melanoma, the possibility of a collision event cannot be ruled out. Finally, we documented a significant concordance among examiners in the diagnosis of the congenital versus acquired nature of the associated naevus. This suggests that the histopathological criteria generally employed to distinguish between congenital and acquired naevi have good reproducibility.

Adult↗