Biomedical subjects
Publications and source records attributed to S Staibano.
Juvenile hyaline fibromatosis is a rare soft-tissue, tumor-like condition that usually arises in children. We report a case characterized by localized lesions and very slow progression. We postulate the existence of two distinct forms of juvenile hyaline fibromatosis--a localized form with very slow growth and a diffuse form with large and rapidly growing tumors.
We report on a primary cutaneous rhabdoid tumour in a 14-month-old child, to the best of our knowledge, the second case in the literature. The tumour showed a multipolypoid gross appearance and classical histological features. The neoplastic cells were positive for keratin and vimentin and most were positive for proliferating cell nuclear antigen. The ultrastructural examination revealed typical intracytoplasmic aggregates of intermediate filaments. The tumour showed a very aggressive course, and the child died 5 months after the diagnosis of cerebral metastasis.
Basal cell carcinoma (BCC) is the most frequent cutaneous neoplasm, with a generally favorable clinical behavior. Sometimes, indeed, it recurs after therapy and/or metastasizes. As point mutations in the coding sequence of the p53 tumor suppressor gene have been implicated in the progression of many human tumors, we studied the expression of p53 protein on this neoplasia. We tested immunohistochemically the positivity for p53 protein (NCL-p53-CM1, YLEM) on 19 cases of morphologically "non aggressive" BCC (BCC1) and on 19 "aggressive" BCC (BCC2), all with one or more relapses and 3 with distant metastases also. Results were related to clinico-pathological and follow-up data. All but one BCC2 were found positive for p53 protein. Conversely, only 2 cases of BCC1 exhibited low immunoreactivity for p53 protein, with high statistical differences between the two groups. No correlation was found between the immunoreactivity, age of patients, and site of the lesions. The availability of immunohistochemistry and the relatively easy interpretation of the results make screening for p53 protein a possibly useful tool in the prognostic evaluation of BCC.
Nucleolar organizer regions (NOR) were investigated on routine paraffin-embedded histologic sections of 11 aggressive basal cell carcinomas that recurred and/or metastasized (BCC2) and 11 nonaggressive basal cell carcinomas (BCC1). The absolute number of NOR per nucleus was higher in BCC2 than in BCC1, and their distribution pattern was also different. In fact, the means of argyrophilic staining of NOR (AgNOR) counts in the two groups of tumors by two observers were 6.56 with a SD of 1.98 for the nonaggressive and 9.48 with a SD of 2.12 for the aggressive basal cell carcinomas. A statistical analysis of these data using the Student's t test confirmed these observations (t = 64.49). Problems in the evaluation of NOR and possible comparison with other experiences are also discussed. The authors conclude that a quantitative assay of AgNOR and perhaps their distribution pattern may provide information useful to recognize BCC2 and hence may be of help in their prognostic prediction.
We investigated the clinicopathological findings in five cases of multicystic mesothelial proliferation (MMP). All masses consisted of multiloculated cysts attached to pelvic organs and sometimes growing into the upper abdominal cavity. The cystic spaces were lined by flattened or cuboidal cells. The stroma showed fibrosis, oedema and chronic inflammation. Immunohistochemistry revealed strong positive staining for cytokeratin and epithelial membrane antigen, and focal positivity for vimentin and carcinoembryonic antigen. The endothelial markers were negative. Electron microscopy showed abundant surface microvilli and well-developed basal lamina. DNA analysis identified euploid cell populations in all cases. All but one case had a previous history of abdominal surgery. Despite the worrying appearance the clinical outcome was favourable in all cases; there was one recurrence. Clinical and pathological data support the hypothesis that MMP represent a reactive mesothelial proliferation and not a neoplastic process.
AIMS AND BACKGROUND: Dermoscopy (dermatoscopy, skin surface microscopy, epiluminescence microscopy) has been increasingly employed in recent years for the preoperative detection of cutaneous melanoma, and dermatoscopic features of pigmented skin lesions have been previously defined using histopathology (HP) as the "key to the code". The aim of the present study was to evaluate the interobserver agreement on the HP diagnosis in a series of epiluminescence microscopy equivocal melanocytic skin lesions. STUDY DESIGN: Ten melanocytic skin lesions were selected on the basis of diagnostic disagreement of at least 2 out of 9 epiluminescence microscopy observers. The histologic specimens from the 10 lesions were examined by 9 HP observers. The agreement of the HP diagnoses was calculated by means of Fleiss' k statistics. RESULTS: The overall HP agreement was less than excellent (k = 0.5). When considering the prevailing epiluminescence microscopic and HP diagnoses, 2 cases were shown to be epiluminescence microscopy false-negative melanomas. Virtually no agreement was found among epiluminescence microscopy observers in 4 cases (40%) or among HP observers in 3 cases (30%). However, only one pigmented skin lesion remained unclassifiable on epiluminescence microscopy as well as HP. CONCLUSIONS: When at least 2 epiluminescence microscopy experts disagree in the evaluation of a given melanocytic skin lesion, even HP consultations may give equivocal results. The need to establish more reliable epiluminescence microscopic and HP criteria by performing an improved and meticulous clinicopathologic correlation, e.g. by using telecommunication via Internet, is emphasized.
Granular cell tumors have been described in many sites throughout the body. To our knowledge, few cases have been described in the literature. We report here the sixth case, in which positivity for lysozyme was also observed for the first time. The problems of the histogenesis and differential diagnosis of this rare variant of basal cell carcinoma are also discussed.
Epithelioid hemangioendothelioma is an uncommon vascular tumor of the soft tissues. Several reports have described this tumor in visceral locations such as liver, lung, and brain. To the best of our knowledge this is the first report of an immunohistochemical and ultrastructural study of a primary epithelioid hemangioendothelioma occurring in the larynx. Difficulties concerning the differential diagnosis and clinical problems arising from surgical therapy in the laryngeal area are also discussed.
Cyclooxygenase (COX), the key enzyme in prostaglandin cascade, is expressed in two isoforms: the constitutive COX-1 and the inducible COX-2. Hyper-expression of COX-2 has been implicated in the pathogenesis of colon-rectal cancer in humans but it appears to play a significant role as a tumour progression factor also in other forms of human cancer, including oral cancer. The aim of this study was to analyze the expression of COX-2, at the protein level, in 45 cases of oral squamous cell carcinoma. Standard immunohistochemical streptavidin-biotin peroxidase analysis was carried out with highly specific antibody against human COX-2 and cell specific markers, in 45 oral squamous cell carcinomas. Our study revealed a moderate to high COX-2 expression in 35 out of the 45 oral squamous cell carcinoma specimens (77.8%). COX-2 expression appeared particularly abundant in the superficial ulcerated layers of relatively well differentiated carcinomas. However, we were unable to assess any statistically significant association between COX-2 hyper-expression and tumor site, tumor grading, tumor size, presence of lymph node metastases, tumor stage and age at onset, respectively. Interestingly, COX-2 expression was detected not only in areas of epithelial dysplasia adjacent to the primary layers (86% of the cases) but also in normal-appearing epithelium at the boundaries of squamous cell carcinoma (77%), indicating a possible involvement in tumour progression by the apparently normal tissue surrounding the lesion. Moreover, intense COX-2 staining was observed in endothelial cells of intra-tumour vessels and extra-tumour vessels adjacent to the tumour nests, in a high proportion of cases (82%). COX-2 positivity was associated with CD34 and VEGF positivity, indicating that these vessels were probably neo-formed ones. From this study as well as from other works, it appears that indeed COX-2 is over-expressed in this important human malignancy. However, further studies are necessary to understand the exact magnitude of this over-expression and, mostly, the possible role of COX-2 in the pathogenesis and progression of oral cancer.
Squamous cell carcinoma (SCC) of the lip is a relatively common malignancy of the head and neck region. Tumour thickness, grading and perineural invasion are significant prognostic indicators. However, there is still the need of new reliable biological markers able to predict the prognosis of the single cases with an unfavourable biological behaviour unpredictable by the classic clinical-pathological parameters. 32 cases of (SCC) of the lower lip were analysed for their clincopathologic features, and immunohistochemical expression of Fas/FasL in neoplastic cells and in inflammatory infiltrate. Moreover the density and phenotype of tumour-infiltrating lymphocytes (TIL) were analysed. The results were related with the follow-up of the patients ranging from 2 to 6 years. The cases with over-expression of Fas/FasL in neoplastic cells and Fas+ in T cells preferentially showed a more aggressive clinical behaviour (P<0.01). Moreover we found an alteration of the normal expression of CD4 and CD8 lymphocyte types in ten cases. This data suggest that the Fas/FasL pathway is involved in the close relation between neoplastic cells and T cells and so in the biological behaviour of these tumours.
We investigated mRNA expression of the genes involved in the apoptotic mechanism in oral squamous cell carcinoma (OSCC) by cDNA microarray. The aim of this study was to identify genes mainly involved in tumorigenesis, comparing the difference of gene expression in neoplastic and non-neoplastic tissues. Eight frozen samples of OSCC and the corresponding normal oral mucosa were treated to obtain mRNA. The mRNA extracted from these specimens was converted into cDNA and analyzed with SuperArray GEArray Q Series Human Apoptosis Gene Array kit. Our results showed that in OSCC there is a different expression of CRADD, FADD, ATM and APAF-1 genes compared to normal mucosa. Real-Time PCR, and Western blot analysis were performed on a separate cohort of patients in order to confirm the results obtained by DNA microarray. Our analysis of apoptotic process through microarray technology confirmed that different molecules could be responsible or favour the imbalance of apoptosis in cancer tissues. Microarray technology has made it possible to analyze the expression of multiple genes in a single experiment. However, most commercial array kits, designed to include as many genes as possible, produce a vast amount of data that often is difficult to interpret. In addition, the cost of equipment is often prohibitive. In contrast, the focused kit used was a complete, affordable and effective method to improve knowledge of molecular specific pathways.
The murine nm23, a putative metastasis suppressor, has three human homologues, NM23-H1, -H2, and -H3b. Several reports have suggested a low metastatic potential for neoplasms with a high expression of NM23-H1 gene, while other studies have not shown this relationship. These apparent differences in the role of NM23 in metastasis suppression might be explained by unability to discriminate between the expression of the two genes NM23-H1 and NM23-H2. The NM23-H2 product is not related to tumor progression and metastasis suppression. Two studies on human oral squamous cell carcinoma (OSCC) have been reported, both showing the NM23 product to be a metastasis suppressor factor. However, none of these two studies distinguished NM23-H1 from NM23-H2. The aim of this study was to detect the protein expression pattern of NM23-H1 product in 24 OSCCs by immunohistochemistry in paraffin-embedded tissues using a monoclonal antibody non-cross-reactive with NM23-H2. The NM23-H1 positive group showed lower frequency of lymph node metastasis, and a better grading than the NM23-H1 negative group supporting the role of NM23-H1 as metastasis suppressor factor which may be useful for predicting tumor metastasis in OSCC.
BACKGROUND: The loss of DNA mismatch repair system was reported in hereditary non-poliposis colon cancer and in other tumours. The aim of this study was to detect the protein expression pattern of hMSH2 and hMLH1 in oral squamous cell carcinoma (SCC) by immunohistochemistry in paraffin-embedded tissues. MATERIALS AND METHODS: 5 specimens, obtained from healthy oral mucosa, and 20 from oral SCC were tested with anti-hMSH2 and anti-hMLH1 monoclonal antibodies. RESULTS: Six cases (30%) showed nuclear positivity in differentiated areas (G1) and cytoplasmic positivity in areas with a lower degree of differentiation, four cases (20%) showed only cytoplasmic positivity, and only one (5%) no staining. One case of oral SCC (5%) showed no hMLH1 staining in the tumoral cells, even if normal squamous epithelium available in this section showed a nuclear positivity; six cases (30%) showed nuclear positivity in differentiated areas (G1) and cytoplasmic positivity in areas with a lower degree of differentiation, three cases (15%) showed only cytoplasmic positivity. CONCLUSIONS: These data suggest that examination of hMSH2 and hMLH1 protein expression by immunohistochemistry is important in oral SCC. The analysis of mismatches expression in these cases of oral SCC might suggest that an absent nuclear staining for both hMSH2 and hML1 could constitute a hallmark of potential phenotype mutator for this type of neoplasia.
Cell-cell adhesion is mediated by cadherins (integral membrane proteins) which form a complex with catenins (cytoplasmatic proteins). Down-regulation of cadherins and more recently of catenins has frequently been detected in many types of human carcinomas, in which it has been associated to tumor progression. While E-cadherin expression has been extensively studied in many forms of human cancers, including oral SCC, less is known about the expression levels of catenins in oral SCCs. The objective of this study was to evaluate the role of these proteins in the carcinogenetic process of the oral cavity. We evaluated by immunohistochemistry beta- and gamma-catenin expression in 30 cases of intraoral squamous cell carcinomas at different degree of cellular differentiation. As already reported for E-cadherin, the beta- and gamma-catenin expression showed an inverse relationship with the degree of differentiation, being the membranous expression of both catenins homogeneously reduced in less differentiated oral squamous cell carcinomas (grade 3). More interestingly, a decreased expression of these molecules was also found at the invasive front of grade 2 and sometimes of grade 1 carcinomas, thus suggesting a more aggressive biological behavior of these cancer cells. An absent staining for both beta- and gamma-catenins could constitute a hallmark of aggressive biological behavior even in tumor still well or moderately differentiated, at least in the peripheral invading front constituted by less differentiated tumor cells.
BACKGROUND: The DNA mismatch repair system (MMR) plays an important role in the maintenance of genomic stability. To date few studies have been performed on hMSH2 and hMLH1 expression and melanoma of the head and neck region. A study of two cases revealed no mutations of the mismatch repair genes hMSH2 and hMLH1. MATERIALS AND METHODS: To verify the possibility of implication of hMSH2 and hMLH1 alterations in melanocytic cancerogenesis, the authors examined the protein expression pattern of hMSH2 and hMLH1 by immunohistochemistry in 9 paraffin-embedded oral melanoma. RESULTS: One case (11%) showed nuclear positivity for hMSH2, 3 cases (33%) showed cytoplasmic positivity, and five cases (55%) showed no staining in the tumoral cells, even if normal squamous epithelium available in this section showed a nuclear positivity. Four cases (44%) showed no hMLH1 staining in the tumoral cells, even if normal squamous epithelium available in this section showed a nuclear positivity. Two cases (22%) showed nuclear positivity, and three cases (33%) showed cytoplasmic positivity. CONCLUSIONS: The analysis of mismatch repair genes can be a new molecular diagnostic tools for the detection of patients at high risk of developing melanoma and other neoplasia, or metastasis and recurrences.
A large number of oral cancer patients show poor or partial response to chemotherapy and the mechanisms are poorly understood. At present, an MDR-1 product, the P-170 glycoprotein, is the best known of the P-170 family and is involved in resistance to natural product-based chemotherapeutics, including taxanes, anthracyclines, vinca alkaloids, podophyllotoxins and camptothecins. Although several reports suggest that P-170 is clinically relevant in haematological malignancies, its role in solid tumours is not well understood. Its overexpression has been found to be correlated with the poor outcome observed in patients treated with chemotherapy and presenting drug resistance. The aim of this study was to detect the protein expression patterns of MDR-1 product by immunohistochemistry in formalin-fixed-paraffin-embedded tissues. For these reasons, 30 oral SCC and 6 healthy oral mucosa specimens were tested with anti-P-170 antibodies using standard streptavidin-biotin-peroxide technique. Immunohistochemistry demonstrated that 4 cases (66.6%) of normal oral mucosa and 24 cases (80%) of oral SCC showed positivity. Four cases (13.4%) showed strong positivity in tumour areas and complete negativity in normal epithelial cells adjacent to the tumour. No staining was observed in stromal structures, with the exception of the lymphocytic compartment that showed a strong staining as reported in literature for CD56+ and CD8+ cells. Four G1 tumours (33%) and 2 G3 tumour (33%) showed strong positivity in areas with a higher degree of differentiation. P-170 positivity in normal epithelial cells of smoker patients, in differentiated area of neoplasia and negativity or zonal positivity in undifferentiated area of tumour suggested that activation of the MDR-1 gene or selection of intrinsically multidrug resistance neoplastic cells may occur at early stages of tumorigenesis of oral cancers, before the real evidence of cellular transformation. Thus the contact with possible chemical carcinogens, such as those of tobacco smoke, may induce activation of MDR-1 gene. This study was conducted only on untreated carcinomas so for this reason it cannot indicate the real incidence of acquired multidrug resistance. The data of MDR-1 product expression by immunohistochemistry in oral SCC might suggest that an overexpression of this protein could constitute a hallmark of potential more aggressive phenotype for this type of neoplasia and a rapid method for pre-screening tumours for a constitutive multidrug resistance in order to orientate the cancer treatment.
Hepatocellular carcinoma (HCC) is a malignant tumor with a marked tendency to spread through the portal system. Metastases from HCC usually involve lungs, surrenal glands, the skeletal and gastroenteric systems, spleen, heart and kidneys. Secondary localizations to the mandible are rare. Generally, bone metastases from HCC appear as osteolytic lesions more likely localized to the ribs, spine, femor, omer, sternum, and then to the mandible. Mandibular metastatic HCC is hemorrhagic in nature because of its hypervascularity. Any diagnostic maneuver that could end in bleeding should be avoided. Non-invasive diagnostic procedures such as computer tomography (CT) scan should be preferred. Among the invasive diagnostic procedures, only fine needle biopsy should be attempted and palliative radiotherapy could be useful for the control of local symptoms. A case report of a hemorrhagic mandibular metastatic HCC that had to be treated surgically, in order to control the severe and profuse bleeding, is presented.
BACKGROUND: Basal cell carcinoma (BCC) is the most frequent tumor of the human skin and generally shows a favourable clinical behaviour. However, a percentage of BCC grows aggressively, infiltrating contiguous structures, sometimes giving distant metastases. MATERIALS AND METHODS: Bcl-2 and p53 protein expression was studied immunohistochemically in 60 cases of BCC (30 non-aggressive, BCC1 and 30 aggressive cases, BCC2) of the head and neck region with a complete clinical follow-up. RESULTS: All the BCC1 showed distinct cytoplasmic staining for bcl-2. The intensity of staining ranged from intermediate to high, with only three cases showing low positivity. Among BCC2, none of the 30 cases showed positivity for bcl-2. Bcl-2 expression was directly correlated with the BCC1 sub-type and a favourable clinical follow-up (p<0.01). Among BCC1, 27 cases were found negative for p53 protein expression while 3 exhibited only a low immunoreactivity. Among BCC2, 11 out of 30 cases showed an intermediate immunoreactivity, and 18 out of 30 exhibited high positivity for p53 protein. The expression of p53 protein correlated inversely with cellular differentiation (p<0.01). CONCLUSION: From the analysis of these results it is reasonable to consider bcl-2 and p53 protein expression as useful discriminating prognostic factors in the evaluation of BCCs of the head and neck region. In fact, the finding of clones expressing bcl-2 in a case of BCC may be indicative of an "indolent" cellular neoplastic phenotype. In other words, bcl-2 could be used as a "clonal marker" of a still favourable clinical behaviour. Conversely, the partial or complete loss of bcl-2-bearing neoplastic clones during histological transformation, with the appearance of clones expressing p53 protein in a BCC could be considered a hallmark of transition from a low-to high-grade malignancy, characterized by the emergence of cellular clones with a more aggressive phenotype, responsible for worse clinical behaviour.