Publications by authors named "Milena Paglierani"

63 Publications

Are biomarkers evaluated in biopsy specimens predictive of prostate cancer aggressiveness?

J Cancer Res Clin Oncol 2016 Jan 26;142(1):201-12. Epub 2015 Jul 26.

Laboratory Cancer Prevention, Cancer Prevention and Research Institute (ISPO), Via Cosimo il Vecchio 2, 50139, Florence, Italy.

Purpose: To evaluate biomarkers involved in biological pathways for prostate cancer (PCa) progression, measured in biopsy specimens, in order to distinguish patients at higher risk for fatal PCa and thus improve the initial management of disease.

Methods: Retrospective case-control study. In 129 PCa patients who underwent ultrasound-guided needle prostate biopsy and subsequent radical prostatectomy from 1987 to 1999 at the University Hospital of Careggi, we evaluated: (1) mRNA expression of the serine 2 (TMPRSS2): erythroblastosis virus E26 oncogene homolog (ERG); (2) expression of matrix metalloproteinases (MMP)-2 and 9 (epithelial and stromal); (3) expression of androgen receptor; (4) expression of prognostic marker Ki67 (MIB1); (5) presence and typing of human papilloma virus; (6) DNA methylation of CpG islands of several genes involved in PCa progression.

Results: The cohort consists of 38 cases (patients with PCa and died of PCa within 10 years from diagnosis) and 91 controls (patients with PCa but alive 10 years after diagnosis). Gleason bioptic score, epithelial MMP expression and SERPINB5 methylation correlated with statistically significant increase in death risk OR. Compared with patients with high level of MMP, patients with low level of MMP had OR for specific death 4.78 times higher (p = 0.0066). After adjustment for age and Gleason score, none of the investigated biomarkers showed increased OR for PCa death.

Conclusions: Our preliminary results suggest that evaluation, in prostate biopsy specimens, of a panel of biomarkers known to be involved in PCa progression is poorly indicative of tumor outcome.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00432-015-2015-1DOI Listing
January 2016

Atypical Spitz tumors in patients younger than 18 years.

J Am Acad Dermatol 2015 Jan 25;72(1):37-46. Epub 2014 Oct 25.

Veneto Institute of Oncology Istituto Oncologico Veneto Istituto di Ricovero e Cura a Carattere Scientifico (IOV IRCCS), Padua, Italy.

Background: Diagnosis and proper management of atypical Spitz tumors in pediatric age are still controversial.

Objective: We sought to investigate the clinicopathological and molecular features of atypical Spitz tumors in patients aged 18 years or younger.

Methods: We performed a retrospective clinicopathological and fluorescence in situ hybridization study on 50 pediatric atypical Spitz tumors.

Results: Parameters that were significantly correlated with a diagnosis of atypical Spitz tumors over Spitz nevus included asymmetry, level IV/V, lack of maturation, solid growth, nuclear pleomorphism, high nuclear-cytoplasmic ratio, atypical and deep mitoses, and more than 6 mitoses/mm(2). In the atypical Spitz tumors group, a significantly higher mitotic rate was observed in prepuberal age (P = .04). The 4-probe fluorescence in situ hybridization melanoma assay did not discriminate atypical Spitz tumors from Spitz nevi. Heterozygous 9p21 loss was found in 3 of 37 cases and homozygous 9p21 loss in 2 of 37 cases. Only 1 child experienced a fatal outcome, showing genetic abnormalities by melanoma fluorescence in situ hybridization probe and a heterozygous 9p21 deletion.

Limitations: The limited number of adverse outcomes did not allow the prognostic analysis of single morphologic features.

Conclusion: Pediatric atypical Spitz tumors are associated with minimal lethal potential. Atypical Spitz tumors require complete excision and careful follow-up while our data do not support any clinical benefit for the sentinel lymph node biopsy procedure and completion lymphadenectomy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jaad.2014.09.049DOI Listing
January 2015

KIT genetic alterations in anorectal melanomas.

J Clin Pathol 2015 Feb 14;68(2):130-4. Epub 2014 Nov 14.

Division of Pathological Anatomy, Department of Surgery and Translational Medicine, University of Florence, Florence, Italy.

Background: Mucosal melanomas (MM) represent a heterogeneous tumour population that exhibits site-specific molecular profiles.

Aims: In a multicentre retrospective study, we investigated KIT aberrations in primary anorectal (AR) melanomas compared with melanoma metastatic to the gastrointestinal (GI) tract.

Methods: Primary AR MM (n=31) and GI metastatic melanoma (n=27) were studied for KIT mutations on exons 11, 13, 17 and 18 by high-resolution melting analysis, direct sequencing and c-KIT expression by immunohistochemistry. Selected cases were also investigated for increased KIT gene copy number by fluorescent in situ hybridisation.

Results: Functional KIT mutations were demonstrated in 11/31 (35.5%) of AR melanomas and in 1/26 (3.8%) of GI melanoma metastases (p=0.004). A significant difference emerged between primary and metastatic MM with regards to KIT-positive immunostaining (p=0.002). Immunohistochemical c-KIT protein overexpression did not correlate with KIT mutational status. Increased KIT copy number was demonstrated in 5/20 AR primary cases.

Conclusions: The rate of functional mutations in KIT is significantly higher in AR MM than in GI metastatic melanoma. KIT protein overexpression does not correlate with KIT mutations and cannot be used for screening purposes. Recognising the molecular heterogeneity of MM helps to identify patients who require a different therapeutic approach.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/jclinpath-2014-202572DOI Listing
February 2015

Inflammatory myofibroblastic tumor: clinical, morphological, immunohistochemical and molecular features of a pediatric case.

Pathol Res Pract 2014 Dec 8;210(12):1152-5. Epub 2014 Apr 8.

Department of Biomedicine, Careggi Hospital, Florence, Italy.

Inflammatory myofibroblastic tumor is an uncommon tumor regarded as "intermediate malignancy". We present the clinical, pathological and molecular features of a mesenteric inflammatory myofibroblastic tumor in a 9-month-old male infant. The patient was referred to Anna Meyer Children Hospital of Florence, Italy, for an asymptomatic abdominal mass measuring about 7cm. The lesion was radically excised, and the postoperative course was uneventful. Histologically, the tumor was composed of spindle cells immunopositive for vimentin and desmin admixed with an inflammatory infiltrate. Rearrangement of ALK gene was demonstrated by FISH and immunohistochemistry (cytoplasmic, perinuclear and punctate immunocoloration). The peculiar punctate ALK immunocoloration suggested a possible unusual ALK gene rearrangement involving the CLTC gene.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.prp.2014.03.011DOI Listing
December 2014

Multiple cutaneous angiosarcomas after breast conserving surgery and bilateral adjuvant radiotherapy: an unusual case and review of the literature.

Case Rep Oncol Med 2014 5;2014:413030. Epub 2014 Mar 5.

Department of Radiation-Oncology, University of Florence, Largo G.A. Brambilla 3, 50134 Florence, Italy.

Breast angiosarcomas (BAs) are rare but serious events that may arise after radiation exposure. Disease outcome is poor, with high risk of local and distant failure. Recurrences are frequent also after resection with negative margins. The spectrum of vascular proliferations associated with radiotherapy in the setting of breast cancer has expanded, including radiation-associated atypical vascular lesions (AVLs) of the breast skin as a rare, but well-recognized, entity. Although pursuing a benign behavior, AVLs have been regarded as possible precursors of postradiation BAs. We report an unusual case of a 71-year-old woman affected by well-differentiated bilateral cutaneous BA, diagnosed 1.9 years after adjuvant RT for synchronous bilateral breast cancer. Whole-life clinical followup is of crucial importance in breast cancer patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1155/2014/413030DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3972881PMC
April 2014

Circulating tumor cells detection and counting in uveal melanomas by a filtration-based method.

Cancers (Basel) 2014 Feb 7;6(1):323-32. Epub 2014 Feb 7.

Department of Translational Medicine and Surgery, Università di Firenze, Firenze 50134, Italy.

Uveal melanoma is one of the most deadly diseases in ophthalmology for which markers able to predict the appearance of metastasis are needed. The study investigates the role of circulating tumor cells (CTC) as a prognostic factor in this disease. We report the detection of circulating tumor cells by Isolation by Size of Epithelial Tumor cells (ISET) in a cohort of 31 uveal melanoma patients: we identified single CTCs or clusters of cells in 17 patients, while the control population, subjects with choroidal nevi, showed no CTC in peripheral blood. The presence of CTCs did not correlate with any clinical and pathological parameter, such as tumor larger basal diameter (LBD), tumor height and TNM. By stratifying patients in groups on the basis of the number of CTC (lower or higher than 10 CTC per 10 mL blood) and the presence of CTC clusters we found a significant difference in LBD (p = 0.019), Tumor height (p = 0.048), disease-free and overall survival (p < 0.05). In conclusion, we confirm the role of CTC as a negative prognostic marker in uveal melanoma patients after a long follow-up period. Further characterization of CTC will help understanding uveal melanoma metastasization and improve patient management.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/cancers6010323DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3980594PMC
February 2014

Hapten-specific TH17 cells in the peripheral blood of β-lactam-induced AGEP.

Allergol Int 2014 Mar 25;63(1):129-31. Epub 2013 Dec 25.

Center of High Excellence, Transfer and Education DENOTHE, University of Florence, Florence, Italy.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2332/allergolint.13-LE-0582DOI Listing
March 2014

Animal-type melanoma: report of five cases with sentinel node biopsy and fluorescence in-situ hybridization analysis.

Melanoma Res 2014 Feb;24(1):47-53

aDepartment of Anatomic Pathology, Dermatopathology Section bDepartment of Plastic Surgery, Regional Melanoma Referral Center, Tuscan Tumour Institute (ITT), S.M. Annunziata Hospital, ASL 10 cDepartment of Critical Care Medicine and Surgery, Division of Anatomic Pathology dDepartment of Dermatological Sciences, University of Florence eDepartment of Molecular and Nutritional Epidemiology Unit, Cancer Prevention and Research Institute, Florence, Italy.

Animal-type melanoma (ATM) is a rare tumor, characterized histologically by a predominantly dermal proliferation of heavily pigmented epithelioid and spindle dendritic melanocytes. Five patients with ATM, who had undergone sentinel node biopsy, were studied: three male and two female, between 4 and 62 years of age (mean, 28.0). Lesion size ranged from 4 to 18 mm and thickness from 0.7 to 5.1 mm. Nodal deposits were found in three patients. Of the patients with positive sentinel nodes, the first showed a minimal nodal involvement in one node, the second multiple deposits in one node, and the third multiple deposits in one sentinel node and a single deposit in another; this last patient also had additional tumor deposits in a nonsentinel regional node. Fluorescence in-situ hybridization tumor analysis proved negative in all cases. All patients are alive and free of disease at 36-95-month follow-up (mean, 53 months). Results showed ATM as a neoplasm characterized by a somewhat high rate of lymph node involvement but relatively low rate of visceral metastases and mortality, appearing as a low-grade malignant tumor.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/CMR.0000000000000033DOI Listing
February 2014

Fluorescence in-situ hybridization and dermoscopy in the assessment of controversial melanocytic tumors.

Melanoma Res 2013 Dec;23(6):474-80

Departments of aHead and Neck Surgery bPlastic and Reconstructive Surgery cClinical and Diagnostic Medicine and Public Health, Division of Clinical Pathology, University Hospital of Modena and Reggio Emilia, University of Modena and Reggio Emilia, Modena dDepartment of Critical Care Medicine and Surgery, Division of Pathological Anatomy, Florence, Italy.

Although the 'gold standard' for melanoma diagnosis remains histopathological analysis, presently dermoscopists play a significant role in the diagnostic process. However, even a combined approach may not allow a clear-cut judgment on equivocal melanocytic lesions. Fluorescence in-situ hybridization (FISH) can offer assistance in the evaluation of chromosome abnormalities associated with malignancies, and its role is emerging in melanoma diagnosis. The aim of this study was to evaluate the diagnostic role of the FISH in the assessment of controversial lesions, defined as those lesions showing discrepancies between dermatoscopic and histological evaluations. Twenty clinically and histologically ambiguous melanocytic lesions were selected. After the first histopathologic diagnosis, a second pathologist examined the specimens in a blinded review for a second opinion and to identify the most suitable areas to hybridize using probes specific to RREB1, MYB, and CCND1 genes and the centromere of chromosome 6. The first histopathological evaluation led to the diagnosis of melanoma in seven cases, whereas the second identified eight cases of malignant melanoma and was in agreement with the first in 65% of cases and with dermoscopy in 40% of cases. Cytogenetic abnormalities detected by FISH are markers of malignancy that can be useful in the characterization of difficult-to-diagnose melanocytic tumors, when the dermatologist and the pathologist have a different opinions.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/CMR.0000000000000020DOI Listing
December 2013

Detection of circulating tumor cells in patients with adrenocortical carcinoma: a monocentric preliminary study.

J Clin Endocrinol Metab 2013 Sep 8;98(9):3731-8. Epub 2013 Jul 8.

Department of Experimental and Clinical Biomedical Sciences, University of Florence, Florence 50139, Italy.

Context: Adrenocortical carcinoma (ACC) is a rare malignancy, the prognosis of which is mainly dependent on stage at diagnosis. The identification of disease-associated markers for early diagnosis and drug monitoring is mandatory. Circulating tumor cells (CTCs) are released into the bloodstream from primary tumor/metastasis. CTC detection in blood samples may have enormous potential for assisting in the diagnosis of malignancy, estimating prognosis, and monitoring the disease.

Objective: The aim of the study was to investigate the presence of CTCs in blood samples of patients with ACC or benign adrenocortical adenoma (ACA).

Setting: We conducted the study at a university hospital.

Intervention: CTC analysis was performed in blood samples from 14 ACC patients and 10 ACA patients. CTCs were isolated on the basis of cell size by filtration through ScreenCell devices, followed by identification according to validated morphometric criteria and immunocytochemistry.

Main Outcome Measure: We measured the difference in CTC detection between ACC and ACA.

Results: CTCs were detected in all ACC samples, but not in ACA samples. Immunocytochemistry confirmed the adrenocortical origin. When ACC patients were stratified according to the median value of tumor diameter and metastatic condition, a statistically significant difference was found in the number of CTCs detected after surgery. A significant correlation between the number of CTCs in postsurgical samples and clinical parameters was found for tumor diameter alone.

Conclusions: Our findings provide the first evidence for adrenocortical tumors that CTCs may represent a useful marker to support differential diagnosis between ACC and ACA. The correlation with some clinical parameters suggests a possible relevance of CTC analysis for prognosis and noninvasive monitoring of disease progression and drug response.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1210/jc.2013-1396DOI Listing
September 2013

A juvenile case of conjunctival atypical nevus.

Diagn Pathol 2013 Apr 22;8:64. Epub 2013 Apr 22.

Department of Experimental Oncology, Mediterranean Institute of Oncology, Viagrande, CT, Italy.

Unlabelled: Melanocytic nevi are the most common tumors of the conjunctiva, accounting for 28% of all neoplastic lesions. These tumors, despite their benign behavior, share some atypical histological features with nevi found in other anatomic sites like the genital and acral regions, globally designated as nevi with site-related atypia. Moreover, in children and adolescents, rapidly growing conjunctival nevi show sometimes worrisome histological patterns in association with a prominent inflammatory infiltrate that may lead to diagnostic problems. In this paper we describe a juvenile compound nevus characterized by marked melanocytic atypia and severe inflammation, which can be considered a rare case of juvenile conjunctival atypical nevus. The final diagnosis relied on morphological and immunohistochemical characterization of the large epithelioid melanocytic cells, and on the results of FISH analysis.

Virtual Slides: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/2973228795724608.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/1746-1596-8-64DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3662158PMC
April 2013

Main clues in the pathologic diagnosis of melanoma: is molecular genetics helping?

Dermatol Ther 2012 Sep-Oct;25(5):423-31

Anatomic Pathology Unit, Department of Oncology, Gaetano Rummo General Hospital, Benevento, Italy.

Although conventional histopathologic examination is still the undisputable mainstay for the diagnosis of melanocytic skin neoplasms, application of molecular testing has experienced tremendous growth and will continue to expand in the future as the need for more specific diagnoses and new targeted therapies evolve. Ancillary molecular methods, including comparative genomic hybridization and fluorescence in situ hybridization, have the potential to provide important new information to challenging cases, and will help improve diagnostic accuracy, particularly in cases in which morphology is not conclusive. Pathologists are increasingly involved in the prospective genotyping of melanoma, which leads to patient stratification in light of the novel personalized therapeutic approaches in the advanced setting.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/j.1529-8019.2012.01485.xDOI Listing
March 2013

Glioneuronal tumor with neuropil-like islands: clinical, morphologic, immunohistochemical, and molecular features of three pediatric cases.

Pediatr Dev Pathol 2012 Sep-Oct;15(5):352-60. Epub 2012 May 17.

Pathology Unit, Anna Meyer Children's Hospital, Florence, Italy.

Glioneuronal tumors with neuropil-like islands are rare. The 1st reported cases were localized in the cerebral hemispheres of adults, showed homogeneous histopathologic features (infiltrating astrocytic growth and neuropil-like islands rimmed by neuronal cells), and had an unfavorable behavior. We report 3 pediatric cases (1 boy and 2 girls, ages 4, 6, and 8 years, respectively). The boy had a cerebral tumor, and the girls had a spinal tumor. The younger girl also had multiple posterior fossa lesions. The boy and older girl underwent a gross total resection. The younger girl underwent a subtotal resection of the spinal tumor; posterior fossa lesions were not surgically treated. The boy and younger girl are in complete remission at 33 and 24 months, respectively, after surgery and subsequent high-dose chemoradiotherapy. The older girl had a recurrence that was partially resected. Afterward, she started high-dose chemoradiotherapy and had an optimal radiologic response at 4 months follow up. Microscopically, the common denominator was the presence of synaptophysin-positive neuropil-like islands. One tumor showed ependymal features (pseudorosettes and punctate epithelial membrane antigen immunopositivity). Two tumors had 1p deletion. 19q deletion, MGMT gene promoter methylation, EGFR amplifications or polysomy, and EGFR, IDH1, IDH2, and TP53 genes mutation analyses yielded negative results. In conclusion, glioneuronal tumor with neuropil-like islands can affect children, arise in the spinal cord, and show ependymal features in its glial component. A high-dose chemoradiotherapy program is effective.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2350/12-01-1147-OA.1DOI Listing
April 2013

MAML2 rearrangement in Warthin's tumour: a fluorescent in situ hybridisation study of metaplastic variants.

J Oral Pathol Med 2012 Sep 15;41(8):615-20. Epub 2012 May 15.

Section of Anatomic Pathology, Department of Critical Care Medicine and Surgery, University of Florence Medical School, Florence, Italy.

Background: Warthin's tumour (WT) is a common benign lesion of the major salivary glands. The nature of WT remains controversial, with particular regard to the presence of clonal chromosomal abnormalities, including the t(11;19) translocation involving the CRTC1 and MAML2 genes, that have been identified in both WT and mucoepidermoid carcinoma. In this study, we focused our attention on metaplastic WT variants, and we conducted a fluorescent in situ hybridisation (FISH) analysis for the presence of MAML2 gene rearrangement.

Methods: Dual-colour FISH analysis was performed on paraffin-embedded sections of eight WTs showing metaplastic changes (five with squamous metaplasia, two with mucinous metaplasia and one with both) using a MAML2 break-apart probe.

Results: Presence of split signals indicative of gene rearrangement was identified in a subset of cells in areas of squamous metaplasia in two samples of WT. No rearrangement was observed in the oncocytic epithelium, in lymphocytes and in areas of mucinous metaplasia.

Conclusions: The presence of a small subpopulation of cells carrying MAML2 rearrangement in areas of squamous metaplasia within WT could predispose these lesions to malignant transformation in mucoepidermoid carcinoma and could represent a molecular link between the two entities.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/j.1600-0714.2012.01159.xDOI Listing
September 2012

Fluorescence in-situ hybridization analysis for melanoma diagnosis.

Histopathology 2012 Apr 18;60(5):706-14. Epub 2011 Oct 18.

Department of Biomedical Sciences and Human Oncology, University of Turin, Italy.

Melanocytic proliferation constitutes a heterogeneous group of lesions with remarkable differences in their biology and clinical outcome. Thus, accurate histological diagnosis of these cases is mandatory to establish the most appropriate surgical treatment and follow-up. Although histological examination alone is usually sufficient to identify melanomas among the greater number of nevi, the definition of the benign or malignant nature of a subset of melanocytic tumours, exhibiting atypical features, is a challenging task. Novel techniques that may assist in the histopathological diagnosis in difficult cases have been extensively researched over recent years. Fluorescence in-situ hybridization (FISH), performed with a panel of four probes, including three locus-specific identifier (RREB1, MYB, and CCND1) genes, seems to represent a sensitive and specific molecular tool for the diagnosis of non-ambiguous melanocytic lesions. Some studies have agreed that FISH may be an ancillary diagnostic instrument, but cannot replace light microscopy, to distinguish benign nevi from malignant melanomas in daily practice. However, in the context of ambiguous melanocytic tumours, results are still controversial, and additional and substantial work is needed to develop reliable probes that may identify, with high sensitivity, specific subsets of ambiguous melanocytic lesions, including spitzoid proliferation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/j.1365-2559.2011.03984.xDOI Listing
April 2012

Primary cerebral myxofibrosarcoma: clinical, morphologic, immunohistochemical, molecular, and ultrastructural study of an infrequent tumor in an extraordinary localization.

J Pediatr Hematol Oncol 2011 Oct;33(7):e279-83

Department of Biomedicine, Careggi Hospital, Florence, Italy.

Herein, we describe an intracerebral primary low-grade myxofibrosarcoma occurring in a 9-year-old boy. The lesion measured 7 cm and occupied the left parieto-occipital region. A gross-total removal of the tumor was performed. Nine months later, radiologic follow-up revealed a local recurrence which was again surgically removed. The patient then underwent radiotherapy and chemotherapy. He was well and disease-free at 6 months follow-up. The tumor was composed of spindle, stellated, and multinucleated cells embedded in a myxoid background. Foci of increased cellularity, pleomorphism, and high mitotic rate were present. The tumor borders were sharply demarcated from the non-neoplastic nervous parenchyma. Immunohistochemical staining showed that the neoplastic cells were vimentine and CD34 positive. Fluorescence in-situ hybridization analyses did not show FUS and EWSR1 gene rearrangements. Primary intracranial myxofibrosarcomas are very rare (to the best of our knowledge, less than 10 published cases in the international literature). We believe each new case should be recorded to produce a better clinical, pathologic, molecular, prognostic, and therapeutic characterization of this lesion.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/MPH.0b013e318211834eDOI Listing
October 2011

Immunohistochemical investigation of tumorigenic pathways in sinonasal intestinal-type adenocarcinoma. A tissue microarray analysis of 62 cases.

Histopathology 2011 Jul 13;59(1):98-105. Epub 2011 Jun 13.

Division of Anatomic Pathology, Department of Critical Care Medicine and Surgery, University of Florence Medical School, Florence, Italy.

Aims: Sinonasal intestinal-type adenocarcinoma (ITAC) is an uncommon neoplasm morphologically similar to colorectal adenocarcinoma, with a well-recognized association with occupational exposure to wood or leather dusts. Here, we analyse several gene products with pivotal roles in tumorigenesis, including p53, p16, deleted in colon cancer (DCC), retinoblastoma, adenomatous polyposis coli, β-catenin, E-cadherin and CD10, and discuss their relation to clinical behaviour and to similar pathways in colorectal adenocarcinomas.

Methods And Results: Immunohistochemical analysis of 62 ITACs was conducted on a tissue microarray. Aberrant expression of p53 and p16 were the most commonly observed alterations (61.3% and 64.5% of cases, respectively). Analysis according to the histological subtype showed that p53 overexpression was less frequent in mucinous ITACs (35.3% versus 71.1%, P = 0.018), while loss of DCC and E-cadherin were observed more frequently in this subtype (76.5% versus 31.1%, P=0.002 and 82.4% versus 31.1%, P<0.001, respectively). No correlation was found between the aberrant expression of these and clinical behaviour while mucinous adenocarcinomas had a significantly worse prognosis, with shorter disease-free interval and overall survival (P=0.005 and P<0.001, respectively).

Conclusions: Mucinous ITACs appear to follow a distinct molecular pathway(s) from the non-mucinous variants, and pursue an aggressive clinical behaviour.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/j.1365-2559.2011.03887.xDOI Listing
July 2011

Atypical Spitzoid melanocytic tumors: a morphological, mutational, and FISH analysis.

J Am Acad Dermatol 2011 May;64(5):919-35

Division of Pathological Anatomy, Department of Critical Care Medicine and Surgery, University of Florence, Florence, Italy.

Background: Identification of the clinical behavior of atypical Spitzoid tumors with conflicting histopathologic features remains controversial.

Objective: We sought to assess whether molecular findings may be helpful in the diagnostic and prognostic assessment of atypical Spitzoid tumors.

Methods: A total of 38 controversial, atypical Spitzoid lesions (≥ 1 mm in thickness) were analyzed for clinicopathological features, chromosomal alterations by fluorescence in situ hybridization (FISH) analysis (RREB1/MYB/CCND1/CEP6), BRAF(V600E) mutation by allele-specific real-time polymerase chain reaction confirmed by sequencing, and H-RAS gene mutation by direct sequencing.

Results: Atypical Spitzoid lesions developed in 21 female and 17 male patients (mean age 22 years). Nine patients underwent sentinel lymph node biopsy and a sentinel lymph node micrometastasis was detected in 4 of these 9 cases. Four additional patients, who did not receive a sentinel lymph node biopsy, experienced bulky lymph node metastases and one experienced visceral metastases and death. Lesions from patients with lymph node involvement showed more deep mitoses (P < .01), less inflammation (P = .05), and more plasma cells (P = .04). FISH analysis demonstrated the presence of chromosomal alterations in 6 of 25 cases. Correlation with follow-up data showed that the only case with fatal outcome showed multiple chromosomal alterations by FISH analysis. BRAF(V600E) mutation was detected in 12 of 16 cases (75%) and H-RAS mutation on exon 3 was found in 3 of 11 cases (27%).

Limitations: Our results require validation in a larger series with longer follow-up information.

Conclusions: FISH assay may be of help in the prognostic evaluation of atypical Spitzoid tumors. Diagnostic significance of BRAF(V600E) and H-RAS mutations in this setting remains unclear.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jaad.2010.05.043DOI Listing
May 2011

Development of bioengineered human larynx.

Biomaterials 2011 Jul 6;32(19):4433-42. Epub 2011 Apr 6.

BIOAIRLab, University Hospital Careggi, Florence, Italy.

To date, only two human laryngeal allotransplants have been reported and, although they were successful, both patients required life-long immunosuppression. A bioengineered human larynx could represent a possible alternative to allotransplantation. Human larynxes were decellularized enzymatically to obtain acellular matrices. Histological and molecular analysis demonstrated that all cellular components and nuclear material were removed. SEM showed that decellularized matrices retained the hierarchical structures of the native larynx, and mechanical tests demonstrated that the decellularization did not significantly impaired the biomechanically properties of the obtained matrices. Immunohistochemical staining found residual angiogenic factors after decellularization, and CAM analysis demonstrated that acellular laryngeal scaffolds induce a strong in vivo angiogenic response. Using a decellularization method, we are now able to obtain, in a short and clinically useful time, natural bioengineered laryngeal scaffolds which could be use for partial or total implantation in humans.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.biomaterials.2011.02.055DOI Listing
July 2011

Tumour suppressor gene TP53 mutations in atypical vascular lesions of breast skin following radiotherapy.

Histopathology 2011 Feb 16;58(3):455-66. Epub 2011 Feb 16.

Division of Pathological Anatomy, Department of Critical Care Medicine and Surgery, University of Florence, Florence, Italy.

Aims: Atypical vascular lesions (AVL) occurring at the site of radiotherapy represent an uncommon but well-documented complication in the setting of breast-conserving therapy for breast carcinoma. Although the biological behaviour of AVL has been regarded as benign, it has been suggested that AVL may represent a precursor of angiosarcoma. A better understanding of the biology of AVL is essential in order to assess appropriate patient management. The aim of the present study was to investigate alterations of tumour suppressor gene TP53 in a series of radiation-induced AVL and angiosarcomas (AS).

Methods And Results: Direct sequencing analysis of the TP53 gene showed the presence of at least one variation in 10 of 12 (83.3%) AVL and in seven of eight (87.5%) AS. The most common alteration in both categories was the P72R polymorphism in exon 4. One angiosarcoma sample carried a pathogenetically relevant disruptive mutation c.592delG, a frameshift deletion in exon 6, causing a premature stop codon.

Conclusions: The presence of TP53 alterations suggests that its mutational inactivation may be implicated in the pathogenesis of radiation-associated vascular proliferations. The common mutational pathway suggested by our data supports the hypothesis that AVL and AS are biologically related entities, most probably representing the extremes of a morphological continuum.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/j.1365-2559.2011.03770.xDOI Listing
February 2011

Prognostic significance of the alterations of the G1-S checkpoint in localized leiomyosarcoma of the peripheral soft tissue.

Ann Surg Oncol 2011 Feb 3;18(2):566-71. Epub 2010 Aug 3.

Department of Human Pathology and Oncology, University of Florence Medical School, Florence, Italy.

Background: The aim of this study was to investigate the expression of cell cycle regulators p53, p16, cyclin-D1, and retinoblastoma (Rb) gene protein in leiomyosarcoma of the peripheral soft in order to identify expression profiles potentially useful for clinical prognostic purposes.

Materials And Methods: A tissue microarray representing 70 localized leiomyosarcomas of the limbs and limb girdles was created with 3 representative cores from each tumor. Immunohistochemical staining was performed for p53, p16, cyclin-D1, and Rb using standard techniques. Staining was scored as either absent-low (<20% of neoplastic cells) or moderate-diffuse (≥20%). Outcome analysis was performed for local recurrence-free survival (LFS), metastatic disease-free survival (MDFS), and disease-specific survival (DSS).

Results: Kaplan-Meier analysis of survival revealed that no single alteration of the factors examined was associated with outcome, but tumors showing concomitant alteration of p16 and p53 were characterized by reduced MDFS and DSS (P = 0.01 and P < 0.001, respectively). In addition, patients who received adjuvant therapy consisting of radiotherapy alone or radiotherapy and chemotherapy had a better DSS than those receiving surgery alone or surgery and chemotherapy (P = 0.05). In multivariate analysis, altered p16/p53 remained the only parameter predictive of MDFS and DSS (P = 0.048, hazard ratio [HR] = 2.488, 95% confidence interval [95% CI] 1.006-5.116; P = 0.043, HR = 2.498, 95% CI 1.029-5.909, respectively).

Conclusions: Accumulation of cell cycle alterations represents a prognostic indicator in localized soft tissue leiomyosarcoma, and in particular altered p16/p53 expression is associated with an unfavorable prognosis. This may help the clinical management of patients with leiomyosarcomas.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1245/s10434-010-1226-6DOI Listing
February 2011

Application of a filtration- and isolation-by-size technique for the detection of circulating tumor cells in cutaneous melanoma.

J Invest Dermatol 2010 Oct 10;130(10):2440-7. Epub 2010 Jun 10.

Department of Critical Care Medicine and Surgery, Dermatology Unit, University of Florence, Florence, Italy.

Analysis of circulating tumor cells (CTC) in the peripheral blood of cutaneous melanoma patients provides information on the metastatic process and potentially improves patient management. The isolation by size of epithelial tumor cells (ISET) is a direct method for CTC identification in which tumor cells are collected by filtration as a result of their large size. So far, ISET has been applied only to CTC detection from epithelial cancer patients, and the technique has never been applied to cutaneous melanoma patients. We herein investigated the presence of CTC by ISET in the peripheral blood of 140 subjects (87 with cutaneous melanomas, 10 subjects undergoing surgery for melanocytic nevi, 5 patients with non-melanoma skin tumors, and 38 healthy volunteers). The identification of the cells trapped in filters as CTC was supported by positivity for immunohistochemical markers and for tyrosinase mRNA by real-time RT-PCR. CTC were neither detected in the controls nor in the in situ melanoma group. In contrast, CTC were shown in 29% of patients with primary invasive melanoma and in 62.5% of metastatic melanoma patients (P<0.01). CTC detection correlated with the presence of mRNA tyrosinase in blood samples, assayed by real-time RT-PCR (P=0.001). CTC detection corroborated by suitable molecular characterization may assist in the identification and monitoring of more appropriate therapies in melanoma patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/jid.2010.141DOI Listing
October 2010

In vitro effects of oestrogens, antioestrogens and SERMs on pancreatic solid pseudopapillary neoplasm-derived primary cell culture.

Cell Oncol 2010 ;32(5-6):331-43

Department of Internal Medicine, University of Florence Medical School, Florence, Italy.

Background: Solid-pseudopapillary neoplasms of the pancreas (SPNs) are uncommon tumours usually frequent in young women. Although the pathogenesis of SPNs is uncertain a potential influence of the sex hormone milieu on the biology of these tumours has been suggested. The controversial expression of oestrogen receptors (ERs) in SPNs, provide a rationale for studying the effects of oestrogenic molecules on SPN development.

Methods: The expression of a large series of hormonal ligands and receptors was evaluated in tissue specimens and in a primary cell culture (SPNC), obtained from a SPN in young female patient. The effects of 17beta-oestradiol (17betaE2), ICI 182,780 and tamoxifen (Tam) on cell replication and growth were examined.

Results: We have established SPNC primary line. Immunocytochemical analysis was positive for vimentin, cyclin D1 and beta-catenin and negative for cytokeratin, CD10 and neuroendocrine markers, in line with the immunostaining features of the tumoral tissue. Expression of ERalpha, ERbeta and progesterone mRNAs was demonstrated in SPNC and tumor tissue. A proliferative and antiproliferative action of 17betaE2 and Tam respectively were proved in SPNC.

Conclusion: In conclusion, we provide the first direct evidence that oestrogenic molecules can influence proliferation of SPNC, offering future strategies in the control of this neoplasia via selective ER modulators.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3233/CLO-2010-0522DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4619239PMC
November 2010

Clear cell carcinoma of the bladder in a patient with a earlier clear cell renal cell carcinoma: a case report with morphologic, immunohistochemical, and cytogenetical analysis.

Appl Immunohistochem Mol Morphol 2010 Jul;18(4):396-9

Department of Human Pathology and Oncology, University of Florence, Italy.

Clear cell transitional carcinoma of the bladder is a subtype of transitional carcinoma that morphologically resembles a clear cell renal cell carcinoma. Although kidney tumors do not frequently metastasize to the bladder, the recurrence after a clear cell renal cell carcinoma has been reported even several years after nephrectomy. We report the case of a male patient to whom radical nephrectomy for a clear cell renal cell carcinoma has been done, with a bladder tumor featuring polygonal cells with abundant clear cytoplasm deeply infiltrating the vesical wall. We discuss the morphologic features, the immunohistochemical staining with a new marker and the UroVysion FISH analysis to achieve a definitive diagnosis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/PAI.0b013e3181d57dceDOI Listing
July 2010

S100A13 is a new angiogenic marker in human melanoma.

Mod Pathol 2010 Jun 5;23(6):804-13. Epub 2010 Mar 5.

Division of Pathological Anatomy, Department of Critical Care Medicine and Surgery, University of Florence, Florence, Italy.

Angiogenesis is critical in melanoma progression and metastasis and relies on the synthesis and release of proangiogenic molecules such as vascular endothelial growth factor (VEGF)-A and fibroblast growth factors (FGFs). S100A13 is a small calcium-binding protein that facilitates the release of FGF-1, the prototype of the FGF family. S100A13 is upregulated in astrocytic gliomas, in which it correlates with VEGF-A expression, microvessel density and tumor grading, and promotes a more aggressive, invasive phenotype in lung cancer-derived cell lines. To investigate the involvement of S100A13 in human cutaneous melanoma, we analyzed a series of 87 cutaneous melanocytic lesions: 14 common acquired melanocytic nevi, 14 atypical, so-called 'dysplastic' nevi, 45 melanomas (17 radial growth phase and 28 vertical growth phase) and 14 melanoma metastases. Main clinical and pathological features, including histotype, Breslow thickness, Clark's level and outcome were recorded. Microvessel density was determined with CD105/endoglin staining. Semiquantitative determination of S100A13, FGF-1 and VEGF-A protein expression was obtained by immunostaining. Quantification of S100A13 mRNA was achieved by real-time PCR. We found that S100A13 was expressed in melanocytic lesions; compared with benign nevi, S100A13 protein expression was significantly upregulated in melanomas (P=0.024), in which it correlated positively with the intensity of VEGF-A staining (P=0.041) and microvessel density (P=0.007). The level of expression of S100A13 mRNA also significantly increased with progression of disease, from radial growth phase (0.7+/-0.7) to vertical growth phase (3.6+/-3.1) to metastases (7.0+/-7.0) (P<0.001). Furthermore, S100A13 mRNA correlated positively with VEGF-A (P=0.023), TNM stage (P=0.05), risk of relapse (P=0.014) and status at follow-up (P=0.024). In conclusion, S100A13 is expressed in melanocytic lesions when the angiogenic switch occurs and it may cooperate with VEGF-A in supporting the formation of new blood vessels, favoring the shift from radial to vertical tumor growth. Therefore, S100A13 may represent a new angiogenic and prognostic marker in melanoma.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/modpathol.2010.54DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2882157PMC
June 2010

Preoperative assessment of HER-2/neu status in breast carcinoma: the role of quantitative real-time PCR on core-biopsy specimens.

Gynecol Oncol 2010 Feb 17;116(2):234-9. Epub 2009 Nov 17.

Department of Gynecology, Perinatology and Human Reproduction, University of Florence, Viale Morgagni, 85 - 50134, Firenze, Italy.

Objectives: Knowledge of HER-2/neu status is mandatory to identify breast cancer patients amenable to trastuzumab treatment. We evaluated the diagnostic performance of quantitative real-time polymerase chain reaction (qRT-PCR) in the preoperative determination of HER-2/neu status in breast cancer, using core biopsy material.

Methods: In a prospective series, qRT-PCR was performed on fresh core biopsy specimens taken preoperatively in 87 patients with breast carcinoma. Cases with qRT-PCR ratio > or = 2.0 were considered to have HER-2/neu amplification. The results of RT-PCR analysis were compared with those of the standard immunohistochemistry (IHC) and Fluorescence in situ hybridization (FISH) methods. Cases with IHC 3+ or with IHC 2+ and FISH showing amplification were considered HER-2/neu positive. All other cases were considered HER-2/neu negative.

Results: qRT-PCR showed HER-2/neu amplification in 13 cases (14.9%), while the standard IHC-FISH combined approach identified 17 HER-2/neu-positive cases (19.5%). Overall, there was concordance between methods in 83 of 87 patients (95.4%). The Spearman's rho correlation coefficient was 0.851; p<0.001. The diagnostic performance for preoperative diagnosis of HER-2/neu status using RT-PCR on core biopsy specimens as compared to standard approach was as follows: sensitivity 76.5%; specificity 100%; positive predictive value 100%; negative predictive value 94.6%.

Conclusions: Quantitative RT-PCR determination of HER-2/neu status from core biopsy specimens provided results comparable to those given by the standard IHC and FISH methods. The use of qRT-PCR on core biopsy material may represent a very useful and easy tool to enhance early identification of HER-2/neu-positive breast cancer patients who, possibly can benefit from trastuzumab treatment.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ygyno.2009.10.067DOI Listing
February 2010

Embryonal tumor with abundant neuropil and true rosettes: morphological, immunohistochemical, ultrastructural and molecular study of a case showing features of medulloepithelioma and areas of mesenchymal and epithelial differentiation.

Neuropathology 2010 Feb 25;30(1):84-91. Epub 2009 Jun 25.

Department of Biomedicine, Careggi Hospital, 50134 Florence, Italy.

Embryonal tumors are a group of malignant neoplasms that most commonly affect the pediatric population. Embryonal tumor with abundant neuropil and true rosettes is a recently recognized rare tumor. It is composed of neurocytes and undifferentiated neuroepithelial cells arranged in clusters, cords and several types of rosettes in a prominent neuropil-rich background. We describe a new case of this tumor. The patient, a 24-month-old female infant, was referred to the Meyer Children's Hospital with a history of right brachio-crural deficit associated with occasional episodes of headache and vomiting. Computed tomography scan and MRI revealed a large bihemispheric mass. The patient underwent two consecutive surgeries. The resultant surgical resection of the tumor was macroscopically complete. The postoperative period was uneventful. On light microscopy the tumor showed a composite morphology: embryonal tumor with abundant neuropil and true rosettes (specimen from the first surgery); medulloepithelioma with mesenchymal and epithelial areas (specimen from the second surgery). The immunohistochemistry evidenced the heterogeneous (neuronal, mesenchymal and epithelial) immunoprofile of tumoral cells. By real-time polymerase chain reaction (RT-PCR), the PTEN gene expression in the tumor was lower than in the five non-neoplastic brain tissues used as control. Mutation analysis did not show any variation in INI-1 and PTEN sequence while P53 analysis showed the presence of homozygote P72R variation. Fluorescent in situ hybridization analysis showed polysomy of chromosome 2 while amplification of N-MYC was not detected. Owing to the rarity of embryonal tumor with abundant neuropil and true rosettes, each new case should be recorded to produce a better clinical, pathological and molecular characterization of this lesion.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/j.1440-1789.2009.01040.xDOI Listing
February 2010

Problems arising in the diagnosis of primary ovarian transitional cell carcinoma after the occurrence of a transitional cell carcinoma of the bladder: a report of a difficult case and a critical review of literature.

Appl Immunohistochem Mol Morphol 2009 Mar;17(2):178-83

Department of Human Pathology and Oncology, University of Florence School of Medicine, Florence, Italy.

Transitional cell carcinoma (TCC) of the ovary is a recently recognized subtype of ovarian surface epithelial-stromal cancer that morphologically resembles a TCC of the bladder. The most frequent metastases to ovaries come from the gastrointestinal tract and from breast carcinoma, but metastatic TCCs from the urinary tract to the ovary have been reported. TCC of the bladder is the sixth most common cancer in European and North American countries and its incidence has been increasing. We recently observed a woman, who previously had undergone endoscopic resection of a TCC of the bladder. She was affected by an ovarian bilateral tumor with features of malignant transitional cell tumor, characterized by papillae with multilayered transitional epithelium infiltrating the ovarian stroma. In this study, we showed the utility of WT1 and a panel of immunohistochemical markers in the difficult differential diagnosis between bladder and ovarian TCC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/PAI.0b013e31818637c5DOI Listing
March 2009

Expression of Notch-1 and alteration of the E-cadherin/beta-catenin cell adhesion complex are observed in primary cutaneous neuroendocrine carcinoma (Merkel cell carcinoma).

Mod Pathol 2009 Jul 24;22(7):959-68. Epub 2009 Apr 24.

Department of Human Pathology and Oncology, University of Florence, Florence, Italy.

Increasing evidence indicates that Notch signaling contributes to physiological processes, including development and differentiation, as well as tumorigenesis, either as a tumor promoter or suppressor, depending on cellular context, expression levels and cross talk with other signaling systems. Recent studies reported absent or minimal Notch-1 expression in neuroendocrine tumors of the lung and gastrointestinal tract, suggesting a tumor-suppressor function of Notch-1. Merkel cell carcinoma is a rare and highly aggressive primary cutaneous neuroendocrine carcinoma. Because no information is available on Notch-1 expression in this tumor, we have investigated a series of 31 Merkel cell carcinoma for Notch-1 immunoreactivity. Immunoreactivities for E-cadherin and beta-catenin were also analyzed. All but 1 Merkel cell carcinoma (30 of 31) retained cytoplasmic and membrane Notch-1 expression in more than 50% of cells. beta-Catenin displayed a prevalent membrane-associated staining in 30 of 31 cases, and 22 cases showed more than 50% of immunoreactive cells whereas nuclear beta-catenin was seen only in 2 of 31 cases. E-cadherin membranous expression was remarkably low, as only 1 of 26 cases was found positive in more than 50% of cells. In contrast with neuroendocrine tumors in other tissues, evident Notch-1 expression was found in Merkel cell carcinoma. This finding does not support a tumor-suppressor function of Notch-1 in Merkel cell carcinoma. Downregulation of E-cadherin and diffuse membranous beta-catenin expression suggest a dysregulation of the E-cadherin/beta-catenin complex in Merkel cell carcinoma. This may contribute to local invasion and distant metastasis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/modpathol.2009.55DOI Listing
July 2009

In vivo characterization of the inflammatory infiltrate and apoptotic status in imiquimod-treated basal cell carcinoma.

Int J Dermatol 2009 Mar;48(3):312-21

Dipartimento di Scienze Dermatologiche, Università degli Studi di Firenze, Florence, Italy.

Background: Imiquimod use in the treatment of basal cell carcinoma (BCC) has proven to be successful in a large percentage of cases, inducing tumor regression; however, the exact cellular mechanism has not been fully clarified.

Aim: To measure the morphological changes in the tumor microenvironment and the markers of apoptosis in skin biopsies from patients with BCC before and after imiquimod treatment.

Methods: In this open label study, skin biopsies obtained from 11 patients with BCC were evaluated before and after imiquimod treatment for: (i) morphological changes in the tumor microenvironment, with specific emphasis on the immunophenotype of inflammatory cells around the tumor; and (ii) markers of apoptosis, including expression of death receptors.

Results: Imiquimod treatment induced a significant increase in the mononuclear inflammatory response. In the majority of cases, the cellular infiltrate was predominantly composed of CD3(+)/CD4(+) T cells, suggesting that the effector response is mediated by CD3(+)/CD4(+) lymphocytes, with a minor cytotoxic and natural killer (NK) component. An increase in the cytotoxic CD3(+)/CD8(+) T-cell population was also observed. Imiquimod treatment was associated with a marked increased in CD20(+) B cells, and a less pronounced enhancement in cells of monocyte-macrophage origin (CD68(+)) surrounding, or within, the tumor. This finding indicates either that macrophages play a minor role in the imiquimod-induced response, or the recruitment of these cells is related to time and dose. Imiquimod treatment decreased CD1A(+) Langerhans cells in the epidermis and increased the number of CD1A(+) dendritic cells within the tumor aggregates. Imiquimod reduced Bcl-2 expression, but no difference was found in Bax, Fas/FasL, and p53 expression in BCC cells.

Conclusions: Our results support the hypothesis that imiquimod activity in the treatment of BCC is partly a result of a pro-inflammatory action mediated by CD3(+)/CD4(+) lymphoid cells and of a pro-apoptotic activity associated with decreased Bcl-2 expression.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/j.1365-4632.2009.03916.xDOI Listing
March 2009