[Show abstract][Hide abstract] ABSTRACT: Human epidermal growth factor receptor 2 (HER2) is considered to be a therapeutic and prognostic marker in the management of breast carcinoma (BC), although discordance rates between primary and metastatic or locally recurrent lesions have been reported.
OncoTargets and Therapy 01/2014; 7:1267-72. · 2.07 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Despite ongoing clinical trials, the efficacy of anti-angiogenic drugs for the treatment of brain metastases (BM) is still questionable. The lower response rate to anti-angiogenic therapy in the presence of BM than in metastatic disease involving other sites suggests that BM may be insensitive to these drugs, although the biological reasons underlining this phenomenon are still to be clarified. With the aim of assessing whether the targets of anti-angiogenic therapies are actually present in BM, in the present study, we analyzed the microvessel density (MVD), a measure of neo-angiogenesis, and the vascular phenotype (mature vs. immature) in the tumor tissue of a series of BM derived from different primary tumors. By using immunohistochemistry against endoglin, a specific marker for newly formed vessels, we found that neo-angiogenesis widely varies in BM depending on the site of the primary tumor, as well as on its histotype. According to our results, BM from lung cancer displayed the highest MVD counts, while those from renal carcinoma had the lowest. Then, among BM from lung cancer, those from large cell and adenocarcinoma histotypes had significantly higher MVD counts than those originating from squamous cell carcinoma (p = 0.0043; p = 0.0063). Of note, MVD counts were inversely correlated with the maturation index of the endoglin-stained vessels, reflected by the coverage of smooth muscle actin (SMA) positive pericytes (r = -0.693; p < 0.0001). Accordingly, all the endoglin-positive vessels in BM from pulmonary squamous cell carcinoma and renal carcinoma, displayed a mature phenotype, while vessels with an immature phenotype were found in highly vascularized BM from pulmonary large cell and adenocarcinoma. The low MVD and mature phenotype observed in BM from some primary tumors may account for their low sensitivity to anti-angiogenic therapies. Although our findings need to be validated in correlative studies with a clinical response, this should be taken into account in therapeutic protocols in order to avoid the adverse effects of useless therapies.
International Journal of Molecular Sciences 01/2014; 15(4):5663-79. · 2.46 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: According to the ToGA trial, HER2 has been shown to be predictive for the success of treatment with trastuzumab in advanced gastric cancer (AGC). A number of studies have analyzed HER-2/neu overexpression in gastric carcinoma and identified the rate of HER2 positivity to be markedly varied. To date, the prevalence of HER2 overexpression in Sicilian people with AGC is unknown. Therefore, in the present study, a retrospective immunohistochemical analysis of HER2 was performed in a cohort of 304 AGC samples that were obtained from the archives of 10 Sicilian anatomopathological diagnostic units in order to verify the positive rate of HER2-positive cases. Furthermore, the characteristics of histotype, grade, stage and Ki-67 expression were also analyzed. HER2 overexpression was encountered in 17.43% of all the gastric adenocarcinomas, which was consistent with the results that have been reported elsewhere in the literature. A progressive increase in HER2 overexpression was observed, from the poorly cohesive histotype to the tubular adenocarcinomas and gastric hepatoid adenocarcinomas. HER2 overexpression was significantly associated with a high grade, advanced stage and high Ki-67 labeling index. Further investigations performed jointly by pathologists and oncologists within the geographical area of the present study should confirm that the association of trastuzumab with chemotherapy results in an improvement of survival in patients with AGC.
[Show abstract][Hide abstract] ABSTRACT: Background Familial spinal neurofibromatosis is a form of neurofibromatosis 1 (NF1), consisting of extensive, symmetrical, histologically proven, multiple neurofibromas of the spinal roots at every level and of all major peripheral nerves sometimes associated with typical NF1 stigmata; most cases underlie NF1 gene mutations.Objectives The objectives of this study are (1) to report the findings in a set of 16-year-old monozygotic twin girls and a 14-year-old boy and (2) to review the existing literature.Methods and Results In this article, we report the cases of three children who (1) had manifested mildly different symptomatic neuropathy (twins, aged 4 years; and a boy, aged 9 years) associated with massive, symmetrical neurofibromas; (2) had few café-au-lait spots with irregular margins and pale brown pigmentation; (3) were presented with, at brain magnetic resonance imaging (MRI), bilateral, NF1-like high-signal abnormalities in the basal ganglia; (4) yielded missense NF1 gene mutations in exon 39; and (5) had unaffected parents with negative NF1 genetic testing as well as discuss 12 families and 20 sporadic and 5 additional cases that presented spinal neurofibromatosis within classical NF1 families (53 cases) that were reported in the literature.Conclusions This article presents the first report on (1) spinal neurofibromatosis in a set of affected monozygotic twins; (2) the earliest onset of the disease; and (3) the occurrence of high signal lesions in the brain at MRI.
[Show abstract][Hide abstract] ABSTRACT: Aim: The aim of this study was to assess both the epidermal growth factor receptor (EGFR) protein expression by immunohistochemistry and the EGFR gene amplification by fluorescence in situ hybridization in meningiomas of different grade, in order to evaluate their possible role in the development of the disease. EGFR protein belongs to the family of tyrosine kinase growth factor receptors, which also includes HER2, HER3 and HER4. Elevated expression or activity of EGFR has been reported in several cancers, including brain tumours. EGFR activation can enhance the malignant potential of epithelial tissues. Methods: We investigated whether there was a difference in the EGFR protein expression and the EGFR gene amplification between the so called de novo malignant meningiomas and recurrent meningiomas with or without malignant progression from a previously lower grade tumor. Our goal was to evaluate if EGFR expression was a useful marker to select patients affected by meningioma with a major risk of recurrences. We also assessed the prognostic value of the EGFR expression on overall survival. Results: Progression from benign meningiomas to atypical or anaplastic meningiomas correlated with an increase in the expression of EGFR protein. Our study shows that EGFR immunostaining in meningiomas directly correlates to the tumor's grade. The EGFR expression did not correlate with the overall survival and the recurrence-free survival of the patients affected by meningioma (de novo, recurrent and progressed). Conclusion: We submit that the EGFR expression is not a useful prognostic element to identify patients with a major risk of meningioma recurrence.
Journal of neurosurgical sciences 03/2013; · 0.53 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: We describe a case of isolated primary laryngeal leishmaniasis in an immunocompetent Italian patient with a previous medical history negative for visceral or cutaneous leishmaniasis, presenting with hoarseness. We also summarize the epidemiological, clinical, and diagnostic features and the therapeutic management of other cases of laryngeal leishmaniasis in immunocompetent subjects, described in the literature. Considering the insidious and nonspecific clinical presentation, the increasing number of different forms of mild or underestimated immunosuppressive conditions, and the number of people travelling in endemic zones, along with the ability of Leishmania amastigotes to survive for a long period in the body, we believe it is important for pathologists and clinicians to be aware of this unusual form of leishmaniasis in order to avoid delayed recognition and treatment. The rarity of the presentation and the lack of guidelines on mucosal leishmaniasis may contribute to the potential undiagnosed cases or delayed diagnosis, the possible relapses, as well as the correct pharmacological and/or surgical therapeutic approach.
Case reports in infectious diseases. 01/2013; 2013:165409.
[Show abstract][Hide abstract] ABSTRACT: Osteoblastoma is a solitary, benign bone tumor that is rarely localized in the frontal sinus. It consists of hypocellular mineralized tissue that may form large masses or irregular trabeculae. A 31 year old man came to our attention with a 7 month history of diplopia, photophobia, frontal headhaches and progressive exophthalmos with proptosis of the left eye. The patient was submitted to computed tomography (CT) which allowed to appraise the extension of the lesion. The mass expanded inside the left frontal sinus and the upper ethmoidal cells invading the left orbital roof. Considering the extension of the tumor, the site and the connections with contiguous structures, a combination of endoscopic endonasal technique with intraorbital approach was performed. At histological examination typical features of benign osteoblastoma were observed. The sites of predilection for the tumor are the long bones, vertebral column, and small bones of hands and feet. Its occurrence in the skull and jaw bones is relatively rare and represents only 15% of all osteoblastomas. To our knowledge, only 5 cases of osteoblastoma of the frontal sinus have been previously reported in the English-language literature. This report describes a case of benign osteoblastoma in a rare site, namely, the frontal sinus with particular attention about the differential diagnosis and the treatment.
European review for medical and pharmacological sciences 11/2012; 16(13):1891-4. · 1.09 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: This study was undertaken to prospectively determine the diagnostic capabilities of magnetic resonance (MR) imaging in detecting myometrial and cervical invasion and lymph node involvement in endometrial carcinoma and to identify the causes of errors in staging endometrial carcinoma. MATERIALS AND METHODS: Twenty consecutive patients with a histological diagnosis of endometrial carcinoma underwent preoperative MR imaging. MR findings were compared with surgical staging, considered as the standard of reference. RESULTS: In assessing myometrial invasion, MR imaging showed 70% accuracy, 80% sensitivity, 40% specificity, 80% positive predictive value (PPV), and 40% negative predictive value (NPV). In detecting cervical invasion, MR imaging had 95% accuracy, 100% sensitivity, 94.4% specificity, 66.7% PPV, and 100% NPV. In evaluating lymph node involvement, MR imaging showed 100% accuracy, sensitivity, specificity, PPV and NPV. Errors in evaluating myometrial invasion were caused by polypoid tumour, adenomyosis and leiomyomas, whereas those in evaluating cervical invasion were caused by dilatation and curettage. CONCLUSIONS: MR imaging is a reliable technique for preoperative evaluation of endometrial carcinoma. Its main limitation is differentiating between stage IA and IB carcinomas, which is not highly important for surgical planning. Cooperation between the gynaecologist and radiologist is mandatory to avoid staging errors.
La radiologia medica 08/2012; · 1.46 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) pathway has a master control role in various cancer-related biological processes as cell growth, proliferation, differentiation, migration, and apoptosis. It also regulates many transcription factors that control microRNAs (miRNAs) and their biosynthetic machinery. To investigate on the still poorly characterised global involvement of miRNAs within the pathway, we profiled the expression of 745 miRNAs in three colorectal cancer (CRC) cell lines after blocking the pathway with three different inhibitors. This allowed the identification of two classes of post-treatment differentially expressed (DE) miRNAs: (1) common DE miRNAs in all CRC lines after treatment with a specific inhibitor (class A); (2) DE miRNAs in a single CRC line after treatment with all three inhibitors (class B). By determining the molecular targets, biological roles, network position of chosen miRNAs from class A (miR-372, miR-663b, miR-1226*) and class B (miR-92a-1*, miR-135b*, miR-720), we experimentally demonstrated that they are involved in cell proliferation, migration, apoptosis, and globally affect the regulation circuits centred on MAPK/ERK signaling. Interestingly, the levels of miR-92a-1*, miR-135b*, miR-372, miR-720 are significantly higher in biopsies from CRC patients than in normal controls; they also are significantly higher in CRC patients with mutated KRAS than in those with wild-type genotypes (Wilcoxon test, p < 0.05): the latter could be a downstream effect of ERK pathway overactivation, triggered by KRAS mutations. Finally, our functional data strongly suggest the following miRNA/target pairs: miR-92a-1*/PTEN-SOCS5; miR-135b*/LATS2; miR-372/TXNIP; miR-663b/CCND2. Altogether, these results contribute to deepen current knowledge on still uncharacterized features of MAPK/ERK pathway, pinpointing new oncomiRs in CRC and allowing their translation into clinical practice and CRC therapy.
Journal of Molecular Medicine 06/2012; · 4.77 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Little information from clinical trials is available regarding the efficacy of trastuzumab treatment in subcentimetric breast carcinomas (BCs). The aim of this study was to verify the existence of correlations between HER2 and hormone receptor status, Ki67 values, grade, histotype and node involvement in a cohort of pT1a,b BCs from an area not widely covered by screening campaigns. A total of 410 pT1a,b BC formalin-fixed paraffin-embedded samples collected from eight Sicilian Anatomo-Pathological Units (APUs) were classified according to the WHO classification and tumour grading was established. Estrogen and progesterone receptor status, Ki67 labelling index and HER2 status were available. Relationships between immunohistochemical data and clinicopathological characteristics were investigated using the Chi-square test; the cohort was analysed with respect to pT1a and pT1b BC as well as to node status. Ductal infiltrating carcinoma was the prevalent histotype in the pT1a and pT1b stages; G2 was a more common tumour grade, with a range between 64.6% and 70% of pT1a and pT1b, respectively. Taking into consideration the lymph node involvement of pT1a,b BC, only 17.1% cases were node-positive without a relevant difference between pT1a and pT1b. No significant differences between pT1a and pT1b BC cases emerged in relation to Ki67 LI, hormone receptors and HER2 status. T1a,b BC cases were stratified by node involvement and a significant relationship was observed with grade as well as with HER2 status. A significant relationship for pT1a cases emerged only for tumour grade, while pT1b cases showed a significant correlation exclusively with HER2 status. Our data clearly support the operative guidelines of the National Comprehensive Cancer Network. Therefore, the combined treatment with trastuzumab plus chemotherapy should be administered only to patients with pT1b or larger BCs. In small HER2-positive pT1a or microinvasive BC, this therapy should be considered on a case-by-case basis, considering tumour grade as the first characteristic.
[Show abstract][Hide abstract] ABSTRACT: Lymphoma is the most common malignant orbital tumor. We describe the imaging features of diffuse orbital follicular lymphoma with extension into the pterygopalatine fossa and infratemporal fossa without bony infiltration.
[Show abstract][Hide abstract] ABSTRACT: Differential diagnosis between vascular parkinsonism (VP) and Parkinson's Disease (PD) is often difficult, due to the overlap in clinical presentation and the lack of specificity at neuroimaging. Aim of the study was to identify a possible reliable marker at SPECT imaging useful to distinguish the two conditions.
We studied 20 PD, 20 VP and 20 essential tremor (ET) patients as control group, who had undergone a cerebral [(123) I] FP-CIT SPECT. A semiquantitative analysis was performed on DaTSCAN SPECT imaging and to establish the degree of asymmetry of the ligand uptake the Striatal Asymmetry Index (SAI) was used.
The binding of the ligand in the most affected side resulted significantly lower in VP than in ET patients but higher compared to PD patients. SAI was significantly higher in PD compared to VP (P < 0.001) and ET (P < 0.001) groups. We found that a cut-off of SAI greater than 14.08 could differentiate PD from VP with a 100% specificity and a 50% sensitivity.
SAI detected using [(123) I]FP-CIT SPECT can be used to differentiate VP and PD with a good degree of certainty.
[Show abstract][Hide abstract] ABSTRACT: Gallbladder metastasis of breast cancer are rare, particularly linked to lobular histotype and synchronous just in 1/4 cases. A review of the literature has been performed aimed to evidence the patterns of gallbladder metastases of breast cancer finding 15 cases to whom we added a 48 years old post-menopausal woman. 3 weeks after surgery for mixed ductal-lobular breast carcinoma she showed at the abdominal ultrasound, performed for staging, diffuse thickening of the gallbladder wall , coherent with a chronic cholecystitis and with the mild right-upper-abdominal pain that the patient complained in the last months. After laparoscopic cholecystectomy, the pathology report showed a metastatic lobular carcinoma of the breast. Two years later she presented with SNC metastases and died four months later. Lobular histotype is the most frequent breast neoplasm associated with gallbladder metastases. Usually metachronous, these metastases are sinchronous in 28% of cases. Symptoms are usually linked to coexisting acute or cronic cholecystitis. Rarely massive invasions lead to acute abdomen or jaundice. Imaging is rarely diagnostic for neoplasm. Our experience and data from literature lead to careful evaluate every anomaly observed in breast cancer patients. A careful evaluation of abdominal symptoms and of routine imaging examinations performed for staging and for treatment planning, could consent to detect and radically treat the metastases and appropriately assign the chemotherapy. Such approach can lead to discrete survival even in these unfortunate patients. Surgeons and gastroenterologists should be aware of the risk hidden behind apparently benign, mild diseases in such patients.
La Clinica terapeutica 09/2011; 162(5):451-6. · 0.33 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Malignant tumors of the paranasal fossae and sinuses represent 0.2% to 0.8% of all malignant tumors in the body and 3% to 6% of other head and neck tumors. It is possible to distinguish 4 different histologic types of sinonasal malignant tumors: squamous carcinoma, adenocarcinoma, adenoid cystic carcinoma, and sinonasal undifferentiated carcinoma. According to the WHO classification, there are 2 main types of adenocarcinomas: intestinal-type (ITAC) and nonintestinal type. ITACs are generally connected with professional exposure to wood and leather dust. The metalloproteinase 9 (ADAM-9) is a type 1 transmembrane protein that has been associated with cancer development and metastases. Our case of poorly differentiated sinonasal ITAC showed moderate to strong cytoplasmic positivity for ADAM-9 in association with moderate membrane staining for c-erbB-2 oncoprotein. In our opinion, the expression of these proteins could explain the tumoral growth and together they could represent the most interesting targets when designing any tumor treatment scheme.
Applied immunohistochemistry & molecular morphology: AIMM / official publication of the Society for Applied Immunohistochemistry 05/2011; 19(3):283-7. · 1.63 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Peripheral primitive neuroectodermal tumor/Ewing's sarcoma (ES) (pPNET/ES) of intracranial origin are very rare. These tumors are characterized by specific translocations involving a gene on chromosome 22q12, the most common being t(11;22) (q24;q12). We report a case of 37-year-old man with pPNET/ES arising in the meninges and bearing the rare translocation t(21;22) (q22;q12). The tumor was composed of sheets and nests of monotonous small cells with round to oval nuclei, finely dispersed chromatin, small nucleolus and scant cytoplasm. We discuss the importance of the differential diagnosis with central primitive neuroectodermal tumors (cPNET).