Biomedical subjects
Publications and source records attributed to M Barbareschi.
We report the case of a 20-year-old man, a professional cyclist, with multiple scaling plaques on his limbs that had been present for 40 days. Our case of tinea corporis presented some peculiarities related to the aetiological agent Microsporum canis and also its mode of transmission.
Disturbances of skin barrier function occur in several skin diseases, e.g., atopic dermatitis (AD), irritant/allergic contact dermatitis (ICD, ACD). Skin barrier damage triggers the production of cytokines that stimulate lipogenesis which may also cause inflammatory processes. The aim of this study was to evaluate the efficacy of a topical skin lipid mixture in the treatment of ICD, ACD and AD. 580 consecutive patients suffering from ICD, ACD or AD were treated with a skin lipid mixture containing ceramide-3 and patented nanoparticles. Patients received the lipid mixture alone or in combination with topical corticosteroids until clearance or for 8 weeks. Both treatment groups statistically improved all parameters considered at week 4 and 8 as compared to baseline. Between the 2 treatment groups, there was a statistically significant difference in favour of combined therapy for (ICD, ACD, AD, respectively): erythema, pruritus and overall disease severity; erythema and pruritus; erythema, pruritus, fissuring and overall disease severity. No statistically significant difference was found for (ICD, ACD, AD, respectively): dryness, scaling and fissuring; scaling, fissuring and overall disease severity; dryness and scaling. Between the 2 ACD treatment groups, there was a statistically significant difference in favour of the skin lipid mixture for dryness. In conclusion, the study shows that balanced lipid mixtures are effective in improving barrier properties and the clinical condition of the skin in contact dermatitis.
Five patients who presented stable bands of hair of a different color with respect to the surrounding hair are reported. In 4 patients this was an isolated finding. One patient also had diffuse linear skin hypopigmentation and other abnormalities. We hypothesize that these 5 cases represent a distinct type of hair heterochromia, possibly because of somatic mosaicism for genes affecting pigmentation.
Myoepithelial cells (MCs) constitute the basal cell layer of normal mammary epithelia, and their identification is of particular diagnostic value because they are retained in most benign lesions while being lost in malignancy. Several MC immunocytochemical markers are currently available for diagnostic purposes, with special reference to smooth muscle-related antigens. p63 is a member of the p53 gene family, and its germline mutations are associated with severe mammary developmental defects in both rodents and humans. Different p63 isoforms have been identified, some of which (DeltaNp63) are preferentially expressed in the epithelial basal cells of different organs and have been considered as possible markers of stem cells/reserve cells. We investigated immunohistochemically 384 samples of normal and diseased human breast, including 300 invasive carcinomas, using four antibodies recognizing all p63 isoforms, or the DeltaNp63 isoforms. Twenty cytologic specimens were also investigated. Furthermore, snap-frozen tissue samples from three fibroadenomas and 10 invasive ductal carcinomas with their paired non-neoplastic tissues and three corresponding lymph node metastases were evaluated for the expression of p63 mRNA by RT-PCR. In normal breast tissue p63 immunoreactivity was confined to the nuclei of MCs. In all benign lesions p63-immunoreactive cells formed a continuous basal rim along the epithelial structures. Stromal cells, and in particular myofibroblasts, were consistently unreactive. Adenomyoepitheliomas showed nuclear staining in most neoplastic cells. A peripheral rim of p63-immunoreactive cells was retained surrounding lobular and ductal carcinoma in situ, although it was discontinuous as opposed to the normal structures. Invasive breast carcinomas were consistently devoid of nuclear p63 staining, with the exception of the two adenoid-cystic carcinomas, of the two ductal carcinomas with squamous metaplasia, and of 11 (4.6%) ductal carcinomas not otherwise specified, showing p63 immunoreactivity in a minor fraction (5-15%) of the neoplastic cells. In comparison with other MC markers, p63 was the most specific, being restricted exclusively to MCs, whereas antibodies to smooth muscle actin and, to a lesser extent, calponin also decorated stromal myofibroblasts. In the cytologic preparations p63 immunoreactivity was a consistent feature of "naked nuclei" and of a subset of cells surrounding benign epithelial clusters. RT-PCR experiments with primers specific for different p63 isoforms documented that normal tissues and fibroadenomas preferentially expressed the DeltaNp63 isoforms. Our study demonstrates that in normal and pathologic breast tissues MCs consistently express the DeltaNp63 isoforms. We suggest p63 as a reliable, highly specific, and sensitive MC marker in both histologic and cytologic preparations. Furthermore, because p63 immunoreactivity in adult epithelia is normally restricted to progenitor cells, it can be speculated that it might be a clue for the identification of the still elusive breast progenitor cells.
The aim of the present study was to assess whether a telemicroscopy system based on static imaging could provide a remote intraoperative frozen section service. Three pathologists evaluated 70 consecutive frozen section cases (for a total of 210 diagnoses) using a static telemicroscopy system (STeMiSy) and light microscopy (LM). STeMiSy uses a robotic microscope, enabling full remote control by consultant pathologists in a near real-time manner. Clinically important concordance between STeMiSy and LM was 98.6% (95.2% overall concordance), indicating very good agreement. The rates of deferred diagnoses given by STeMiSy and LM were comparable (11.0% and 9.5%, respectively). Compared with the consensus diagnosis, the diagnostic accuracy of STeMiSy and LM was 95.2% and 96.2%. The mean viewing time per slide was 3.6 minutes, and the overall time to make a diagnosis by STeMiSy was 6.2 minutes, conforming to intraoperative practice requirements. Our study demonstrates that a static imaging active telepathology system is comparable to dynamic telepathology systems and can provide a routine frozen section service.
Telemetric, intraoperative frozen section diagnosis may be a useful tool for rural hospitals lacking an in-house pathology service. As a part of a Health Ministry Project on Telemedicine in Trentino (northern Italy), we developed a static telemicroscopy system (STeMiSy). This system connects the rural hospital of Cles with the main hospital of Trento. The two hospitals are 40 kilometers apart, and the road connecting the two towns runs across the mountains and has a heavy traffic. Before putting STeMiSy into practice, we tested the software and hardware on the LAN of the regional hospital system, by connecting the pathology services of Trento and Rovereto (20 kilometers apart). This test phase lasted three months and has not revealed major problems in the LAN nor in the robotic microscope, which was always precise and reliable. The quality of the images and the speed of transmission were largely sufficient for intraoperative frozen section diagnosis. Minor details of the histological slides were not always appreciated on the panoramic view. This loss of some details may be due to the quality of the panoramic view, which represents the 'surfing map' to read the cases. Nevertheless, the recognition of these small details was not so relevant as to change the surgical approaches. An audioconference system, utilizing the same transmission channel, not only slightly slowed the transmission but also caused some instability to the system. The audioconference system has therefore been abandoned, and when necessary we used the normal telephone. Macroscopic images of the whole surgical specimen, the surgeon's responsibility for the sampling, good technical quality of the slide, and good training will allow us to perform remote frozen section diagnosis in the absence of the pathologist. We believe that the main, and probably only, difficulty for this approach is not of a technical nature, but reflects the pathologist's resistance to making a remote video diagnosis.
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p27(Kip1) (p27), a cyclin-dependent kinase inhibitor, has an important role in the progression of cells from G(1) into S phase of the cell cycle. p27 may act as a tumor suppressor, and several reports suggest that loss of its expression in breast carcinoma is related to tumor progression and poor prognosis. We evaluated p27 immunohistochemical expression in 512 consecutive cases of breast carcinoma with 9 years of median-term follow-up. p27 expression was heterogeneous and frequently less intense than in normal cells. Low p27 expression (<50% of reacting cells) was associated with grade III tumors, N0 status, estrogen receptor-negative status, and low cyclin D1 expression. In the whole series of cases, p27 expression did not predict outcome. In node-negative cases (249 patients), high p27 expression indicated poor prognosis. p27 was not prognostically relevant in the group of 223 patients with pT1 disease or in the group of 154 patients <50 years of age. We also investigated the prognostic value of the combined expression of p27 and cyclin D1, but no differences in survival were seen in this bivariate analysis.
BACKGROUND: An association between alopecia areata (AA) and coeliac disease has recently been reported. AIM: The aim of this paper was to evaluate the possible effect of a gluten-free diet (GFD) on the new growth of hair in 5 alopecic patients with CD. METHODS: CD was diagnosed in 5 patients with AA (universalis in 3 cases and patchy in 2 cases). The diagnosis of CD was based on serological and histological standard criteria. RESULTS: In all patients the GFD resolved CD clinically, serologically and histologically but had no effect on the course of alopecia. CONCLUSION: AA and CD, when associated, present different responses to a GFD and have an independent course.
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The WAF1/CIP1 gene product, p21, an inhibitor of cyclin-dependent kinases, is a critical downstream effector in the p53 pathway. The expression of p21 in human neoplasms is heterogeneous, and may be related to p53 functional status. We evaluated p21 immunoreactivity in 103 colorectal carcinomas (CC) in relation to the p53 gene and protein alterations and clinico-pathologic parameters. High p21 expression (more than 10% reactive cells) was seen in 39% of cases. p21 staining was heterogeneous and often detected in clusters of tumour cells; in some tumours p21 staining was more pronounced in superficial areas. No relation was seen between p21 immunoreactivity and site of the tumours (right vs left), TNM stage and grade. p21 expression was related to p53 status as evaluated with IHC or with SSCP analyses, low p21 expression usually being associated with p53 protein overexpression (P=0.048) and p53 gene alteration (P=0.005). The strongest associations were seen when the combined p53/p21 immunophenotype was compared with p53 gene alterations (P=0.0002). These data support the hypothesis that p21 expression in CC is mainly related to p53 functional status, suggesting that p21 expression could be an interesting adjunct in the evaluation of the functional status of the p53 pathway in CC.
Steroid receptor analysis is the only widely accepted prognostic/predictive marker in breast cancer (BC) treatment. In the present study we evaluated the prognostic role of ER/PgR with p53 and Bcl2, in a series of 277 BC (153 pN1/2, 122 pNO, 2 pNx) with a long-term follow-up (67 months for DFS, 75 months for OS). Our results, besides confirming the usefulness of ER immunohistochemical expression as a prognostic marker, showed that PgR expression alone had a borderline/not significant prognostic value in the whole series (p=0.08 for DFS and p=0.09 for OS), while showed to be prognostic in N+ cases (p=0.02 for DFS and p=0.03 for OS). PgR prognostic value, however, was not independent at the multivariate analysis. By combining ER with PgR, p53 and Bcl2, we showed that ER/p53 and ER/Bcl2 phenotypes had a better discriminant role than ER/PgR phenotype. The ER+/p53+ phenotype was at higher risk of relapse/death as compared with ER+/p53- phenotype. Conversely ER-/p53+ phenotype showed the most unfavourable prognosis. Similar results could be observed concerning ER/Bcl2 phenotypes. Our study showed that the combined evaluation of ER/PgR weakly enhanced the prognostic/predictive power of ER status alone. On the contrary, the combined evaluation of ER/p53 and ER/Bcl2, improved this prognostic/predictive capability and allowed the separation of ER positive and ER negative cases into subgroups with different prognosis.
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p27 KIP1 is a cyclin dependent kinase inhibitor, which may act as a potential suppressor gene. Several lines of evidence support the hypothesis that reduced p27 KIP1 expression is related to uncontrolled cell proliferation and tumorigenesis. Low immunohistochemical expression of p27 KIP1 in human neoplasm seems related to tumor progression and poor prognosis. In breast cancer, low p27 is associated with high tumour grade and loss of oestrogen receptor, and it has been suggested that low p27 KIP1 is a powerful and independent prognostic marker of poor clinical outcome. There are however some discrepant results: a few studies, some of which conducted on large series of patients, do not support an independent role of p27 KIP1 as a prognostic marker. We are indeed faced with an intriguing hypothesis, but many more studies are needed to evaluate the real value of p27 KIP1 as a prognostic marker.
Bax and Bcl2 are functionally antagonistic proteins which control apoptosis, whose expression in human tumours could be of prognostic value. We evaluated Bax and Bcl2 expression in 239 breast carcinomas (99 N0, 140 N1/2) with long term follow-up (median 79 months, range 11-140) in relation to clinico-pathologic parameters, clinical outcome, adjuvant therapy and expression of oestrogen receptor protein and p53. The prognostic value of Bax was investigated in the whole series of patients and in subgroups of homogeneously staged and treated patients (i.e., node-negative, N1/2 CMF-treated, N1/2 tamoxifen-treated). Bax immunostaining was cytoplasmic and heterogeneous. Cases were scored as Bax-positive if there were more than 20% reacting cells. High Bax expression was associated with positive nodal status (p = 0.03) and high Bcl2 expression (p = 0.01) and was more frequent in high-grade tumours. In the node-negative subgroup, Bax expression was associated with small tumour size. No association was seen with other parameters or with clinical outcome in any subgroup of patients. Since the apoptotic rate of a tumour is influenced by the ratio Bcl2/Bax, we investigated the combined effects of Bax and Bcl2 expression in relation to clinical outcome. However, no differences in survival were seen in the Bcl2-negative and Bcl2-positive groups when they were subdivided on the basis of the level of Bax expression and vice versa. In experimental systems, p53 is a direct transcriptional activator of the human bax gene. However, we could not observe any relation between Bax and p53 expression. We investigated whether the combined p53/Bax expression could have any prognostic value since it is predicted that tumours with normal p53 expression and concurrent high levels of Bax should be less aggressive and more susceptible to therapy. However, while p53 itself was of prognostic value, Bax expression was not related to prognosis in p53-negative or in p53-positive groups.
Among the major regulators of the G1 restriction point are cyclin D1 and the retinoblastoma gene product (RB). In non-small cell lung cancer (NSCLC), the cyclin D1 gene is amplified/over-expressed in almost 50% of cases, and RB is inactivated in 6-32% of cases. It is of interest to evaluate concurrently the alterations of both genes on the same series of NSCLCs, to investigate whether cyclin D1 and RB alterations are alternative pathways leading to inactivation of the G1 restriction point or if they can occur in the same tumor, possibly exerting an additive effect on cancer progression. We investigated a series of 57 NSCLCs, analyzing cyclin D1 and RB at the gene and protein levels by Southern blot, Northern blot and immunohistochemistry. The cyclin D1 gene was amplified in 18 cases, cyclin D1 immunoreactivity was seen in 25 tumors. Amplification and expression were significantly associated. RB immunohistochemical expression was absent in 9 of 42 informative cases. RB mRNA expression was low to absent in 9 of 45 informative cases, cyclin D1 amplification was associated with normal RB mRNA, and cyclin D1 over-expression was associated with normal RB immunoreactivity, supporting the hypothesis that alterations of cyclin D1 and RB are alternative mechanisms by which tumor cells may escape the G1 restriction point. A concurrent alteration of RB and cyclin D1 was seen in a small subset of NSCLCs. Abnormalities of cyclin D1 and/or RB at the gene and/or expression level were present in more than 90% of cases, stressing that cyclin D1 and/or RB alterations represent an important step in lung tumorigenesis.