Genetic clonal mapping of in situ and invasive ductal carcinoma indicates the field cancerization phenomenon in the breast

Summary Nearly 80% of well-differentiated in situ duct carcinomas (g1 DCIS) have been shown to be multicentric (multilobar) lesions, while most in situ poorly differentiated duct carcinomas (g3 DCIS) were unifocal (unilobar) lesions. Here we present a clonality study of 15 cases of DCIS, all showing multiple foci. Twelve of these cases were associated with an invasive duct carcinoma. Fifteen cases of female breast cancer patients all showing multiple DCIS foci (5 g1 DCIS, 5 g2 DCIS, 5 g3 DCIS) were randomly selected and histologically studied using large histological sections. Care was taken to laser-microdissect DCIS foci that were most distantly located from one another in the same large section, and pertinent cells were genetically studied. Invasive duct carcinoma and ipsilateral lymph node metastases and/or contralateral lesions, whenever present, were additionally microdissected. DNA of neoplastic cells was purified, and the mtDNA D-loop region was sequenced. Genetic distance of different foci from the same case was visualized by phylogenetic analyses using the neighbor-joining method. Patients ranged in age from 36 to 87 years (mean 65.1). All 9 cases of widely spread DCIS were not clonal. Four of 6 cases that showed multiple adjacent foci were clonally related on mtDNA analysis. In the present series, 11/15 DCIS appeared as multiple synchronous primary breast tumors, genetically not related to one another. The present data enhance the view that breast can also show the field cancerization phenomenon, paralleling what has already been proposed in other organs

Predictive Role of p53 Protein as a Single Marker or Associated to Ki67 Antigen in Oral Carcinogenesis

p53 over-expression has been proposed as a reliable marker associated to oral carcinogenesis, although only about 50% of oral carcinomas (OSCC) are associated with p53 over-expression and even p53-negative lesions can progress to OSCC. The aim of the study was to determine whether the combination of p53 over-expression and p53 low-expression associated with Ki67 over-expression (high Ki67/p53 ratio) could lead to a more sensitive parameter. Immunohistochemical expression of Ki67 and p53 was measured in 54 specimens from OSCC; 27 specimens from moderate/severe epithelial dysplasia; 32 specimens from oral leukoplakias without epithelial dysplasia, and 13 specimens with normal epithelium. p53 over-expression was found in 31 (53%) samples from OSCC, in 10 (37%) samples from severe dysplasias, and in 5 (15%) samples from non-dysplastic lesions, while the combination of high p53 values with high Ki67/p53 ratio was observed in 93% of OSCC, in 81% of dysplastic lesions, and in 50% of non-dysplastic lesions. This parameter may have a clinical implication to detect early lesions with an impairment of p53 pathway, and probably at risk of progress to OSCC

Low-grade myofibroblastic sarcoma of the gingiva

Low-grade myofibroblastic sarcoma is a malignant tumour from myofibroblasts, which has only recently become clearly defined. It represents a rare entity developing in the soft tissues of the head and neck. About 20 cases have been reported in the oral cavity, especially in the tongue and bone, while gingiva as the primary site has been described only once to date. Diagnostic methods include histology and immunohistochemistry. The present report concerns a case of a 37-year-old man who presented with a persistent gingival ulcerated swelling that was interpreted for a long time as a gingival epulis. A low-grade myofibrosarcoma was diagnosed and the patient underwent a segmental osteotomy of the mandibular symphisys for complete excision. There was no sign of recurrence or metastatic disease during the 18-month postoperative period

Molecular characterization of strains of Clostridium difficile isolated from hospitalized geriatric patients

Introduction. Clostridium difficile (Cd) is a spore-forming, gram positive anaerobic bacillus. It can be found as commensal in the human intestinal flora. Cd is the etiologic agent of pseudomembranous colitis and the most common cause of nosocomial antibiotic-associated diarrhea. The pathogenic strains produce toxins (A and B) with cytotoxic effects on intestinal epithelium. Some strains producing binary toxin, cause more severe infections. So far it is not known the specific role of this toxin. The major risk factors for acquiring this infection are: advanced age (over 65), underlying disease, severity of illness, antibiotic exposure and prolonged hospitalization. The purpose of our work was to perform a molecular characterization of Cd strains isolated from patients hospitalized at ASP Pio Albergo Trivulzio. We also performed the analysis of sequential isolates in order to verify if the recurrent infections were due to relapse or reinfection. Methods. A total of 100 C.d. isolates were collected from 75 symptomatic patients from 6 different hospital wards. The strains were cultured on blood agar plates (CD agar \u2013 bioM\ue9rieux) in an anaerobic atmosphere for 48 h at 37\ub0C. The identification of species was performed using Vitek automated system (bioM\ue9rieux). The molecular typing was performed by "ribotyping" according to the method described by Bidet et al., using the 16 S (5'-GTGCGGCTGGATCACCTCCT-3 ') and 23 S (5'-CCCTGCACCCTTAATAACTTGACC-3') sequences. Furthermore, all strains were subjected to PCR to detect the presence of the gene coding for binary toxin. Results. The analysis of patterns obtained by ribotyping showed 14 different ribotypes. None of the strains tested was found to produce binary toxin. Conclusions. The data obtained indicate that there is a considerable spread between the same ward in respect of the spread between different wards. For this phenomena we can assume that the spread has been fostered by the movements of patients in different rooms and that the environment is a possible source of infection. Most of the sequential samples belong to the same ribotype indicating that the recurrent infections may be due to relapse from treatment failure or reinfection with the same strain. The lack of toxin-producing strains binary allows for the time being, not to further increase the rate of mortality

Comparison between echo-color doppler sonography features and angioarchitecture of thyroid nodules.

This study compared echo-color Doppler sonography features of thyroid nodules with the 3-dimensional reconstruction to find parameters useful for the preoperative diagnosis. Forty nodules relative to 29 patients were examined with echo-color Doppler before surgery. After histologic diagnosis, blocks were deparaffinized and prepared for 3-dimensional examination using a stereomicroscope. Echo-color Doppler type I nodules (8 nodules) always corresponded to colloid goiter. Type II and III nodules corresponded to colloid goiter with intralesional hemorrhage or were associated with hyperplastic nodules, follicular adenoma, follicular carcinoma minimally invasive, papillary carcinoma, and medullary carcinoma. Of interest was that 9 of 11 follicular lesions were characterized by a large central vessel, which was also evident in echo-color Doppler images. This architectural pattern is not seen in benign nodules or in papillary carcinomas. Comparison with histology suggests that echo-color Doppler images can visualize vessels showing a muscular wall