Aldo Vecchione

Human herpesvirus 6 infection in neoplastic and normal brain tissue

The presence and variant distribution of human herpesvirus 6 (HHV‐6) was investigated by a nested polymerase chain reaction (PCR) in 118 biopsies from patients affected by nervous tissue tumor (115 primary tumors and 3 metastasis) and in 31 autopsy samples from the brain of healthy individuals. HHV‐6 DNA sequences were detected in normal and neoplastic nervous tissue at a frequency of 32% and 37%, respectively. In both tissues, variant A was three times more frequent than the variant B. Peripheral blood lymphocytes (PBLs) derived from seven tumor affected patients contained the same variant as their respective brain sample, as judged by PCR. The expression of HHV‐6 encoded immediate early protein p41 was detected by immunohistochemistry in neoplastic but not in normal brain. This may reflect viral reactivation from latency in immunocompromised patients. The seroepidemiological data indicated a frequency distribution of anti‐HHV‐6 antibodies in patients with brain tumors similar to that found in healthy donors. J. Med. Virol. 63:45–51, 2001.

Quantitative analysis of CEA expression in colorectal adenocarcinoma and serum: Lack of correlation

Tissues and sera from 110 patients diagnosed with colorectal primary carcinoma, 20 patients with benign colorectal diseases and 31 healthy donors were subjected to quantitative CEA analysis. Multiple samples from tumor lesions and autologous histologically normal mucosa (10 cm from the tumor) were obtained at the time of surgery (cancer patients) or endoscopy (benign patients and healthy volunteers). CEA content was measured in protein extracts obtained from these tissues using a quantitative RIA method. A limit of normality for CEA content was established as 300 ng/mg of protein. When this was taken as cut‐off, 104 of 110 (94.5%) tumor lesions and 51 of 110 (46.4%) autologous histologically normal colonic mucosa from cancer patients had elevated CEA levels. No correlation with stage of disease was found, while a correlation was observed with degree of tumor differentiation. A statistically significant difference between CEA content in tumor lesions and in histologically normal mucosa from cancer patients was observed (p = −0.001). Moreover, CEA content was statistically higher in the normal mucosa from cancer patients than in that from healthy donors (p = 0.005). CEA content in tissue specimens from benign lesions differed significantly from that in tissue from healthy donors (p = 0.005) and in carcinoma lesions (p < 0.001). The highest CEA content was observed in benign lesions with severe dysplasia. No statistical correlation between CEA content in carcinoma tissues and serum CEA levels (r = 0.195, p = .13) was found. Therefore, in considering diagnosis or therapy with anti‐CEA MAbs for colorectal‐carcinoma patients, or potential therapies with anti‐CEA recombinant vaccines, serum CEA levels should not be taken as indicating CEA expression in tumor lesions. Int. J. Cancer 72:949–954, 1997.

Value of cytology as an adjunctive intraoperative diagnostic method. An audit of 2,250 consecutive cases.

OBJECTIVE To evaluate the role of intraoperative cytology (IC) in the improvement of diagnostic accuracy obtained by frozen section (FS) alone. STUDY DESIGN Comparison of 2,250 intraoperative cytologies performed along with frozen sections, with the final diagnoses achieved on paraffin sections. RESULTS In 18 cases the diagnoses were deferred until the paraffin sections at the time of intraoperative consultation. The diagnostic accuracy in distinguishing benign from malignant lesions by combined intraoperative cytology and frozen section was 99.2%. The accuracy rate is significantly higher than that reported in large series based on frozen section preparations alone. Sensitivity and specificity were, respectively, 98.2% and 100%. The diagnostic accuracy of each technique alone was 94.9% for FS (sensitivity 89.9%, specificity 97.9%) and 96% for IC (sensitivity 94.9%, and specificity 96.8%). Although specific diagnoses were more frequently formulated on the bases of frozen section examination, FSs were not diagnostic in 113 case in which cytology allowed a specific diagnosis. CONCLUSION Our results emphasize the increasingly important diagnostic role of intraoperative cytology as an adjunct to frozen section. The approach does have limitations.

Myc Down-Regulation Sensitizes Melanoma Cells to Radiotherapy by Inhibiting MLH1 and MSH2 Mismatch Repair Proteins

Purpose: Melanoma patients have a very poor prognosis with a response rate of <1% due to advanced diagnosis. This type of tumor is particularly resistant to conventional chemotherapy and radiotherapy, and the surgery remains the principal treatment for patients with localized melanoma. For this reason, there is particular interest in the melanoma biological therapy. Experimental Design: Using two p53 mutant melanoma models stably expressing an inducible c-myc antisense RNA, we have investigated whether Myc protein down-regulation could render melanoma cells more susceptible to radiotherapy, reestablishing apoptotic p53-independent pathway. In addition to address the role of p53 in the activation of apoptosis, we studied the effect of Myc down-regulation on radiotherapy sensitivity also in a p53 wild-type melanoma cell line. Results: Myc down-regulation is able per se to induce apoptosis in a fraction of the cell population (∼40% at 72 hours) and in combination with γ radiation efficiently enhances the death process. In fact, ∼80% of apoptotic cells are evident in Myc down-regulated cells exposed to γ radiation for 72 hours compared with ∼13% observed after only γ radiation treatment. Consistent with the enhanced apoptosis is the inhibition of the MLH1 and MSH2 mismatch repair proteins, which, preventing the correction of ionizing radiation mismatches occurring during DNA replication, renders the cells more prone to radiation-induced apoptosis. Conclusions: Data herein reported show that Myc down-regulation lowers the apoptotic threshold in melanoma cells by inhibiting MLH1 and MSH2 proteins, thus increasing cell sensitivity to γ radiation in a p53-independent fashion. Our results indicate the basis for developing new antitumoral therapeutic strategy, improving the management of melanoma patients.

Human papillomavirus in virgins and behaviour at risk

Human papillomavirus (HPV) infection is one of the most common sexual transmitted diseases (STDs). We compared two groups of virgins with genital HPV lesions to evaluate the behaviour at risk in the transmission of HPV infection. Partners were also examined. HPV lesions were detected in 88 virgins, who have never had sexual intercourse. This can be due to vertical transmission, fomities and skin-to-skin contact. Many other hypothesis can be proposed to explain HPV genital infection, however, further studies are required.

High Frequency of Human Papillomavirus Detection in Urinary Bladder Cancer

We investigated the presence of human papillomaviruses (HPVs) types 16 and 18 DNA in formalin-fixed, paraffin-embedded tissues from the urinary bladder (46 transitional carcinomas and 10 non-neoplastic normal urinary samples) to find a possible role for HPV types in urinary tract cancerogenesis. The analysis was performed using polymerase chain reaction followed by filter hybridization with oligonucleotide-specific probes. The HPV16 and/or HPV18 genomes were detected in 23 of 46 (50%) bladder carcinomas and in none of 10 (0%) non-neoplastic urinary samples. These results suggest that HPV16 and 18 may carry a risk for the development of malignancy in the urinary tract as it occurs in the anogenital regions.

Performance of cytology and colposcopy in diagnosis of cervical intraepithelial neoplasia (CIN) in HIV-positive and HIV-negative women.

Performance of cytology and colposcopy in diagnosis of cervical intraepithelial neoplasia (CIN) in HIV‐positive and HIV‐negative women

Oncosuppressor proteins of fragile sites are reduced in cervical cancer

FHIT and WWOX are tumor suppressor genes that span the common fragile sites FRA3B and FRA16D, respectively. To analyze possible synergisms among these genes in cervical cancer progression, we considered 159 cervical intraepithelial neoplasias, and 58 invasive squamous cell carcinomas of the uterine cervix. All cases were previously selected as high risk HPV. FHIT and WWOX proteins were examined by immunohistochemistry and their expression was inversely correlated with precancerous vs. invasive lesions. Statistics among biological markers indicated an association between FHIT and WWOX. Protein expression of these two genes was also absent or reduced in cancer cell lines. Thus, WWOX may be considered as a novel important genetic marker in cervical cancer and the association between the altered expression of FHIT and WWOX may be a critical event in the progression of this neoplasia.

Carbon and Hemosiderin-Laden Macrophages in Sputum of Traffic Policemen Exposed to Air Pollution

In this study, we evaluated (a) quantitative modifications of dust cells and siderocytes and (b) qualitative modifications (i.e., cellular changes and inflammatory infiltrate) in sputum of 164 traffic policemen occupationally exposed to environmental pollution in an urban area. Such modifications were correlated with time of exposure and smoking habits. Seventy-three (45%) of the policemen were smokers, and a control group of 119 nonexposed individuals (24% smokers) who resided in a rural district near Perugia, Italy, were examined. The sputa, which was collected for 3 d, were smeared on glass slides stained according to Papanicolaous and Perls methods. The mean numbers of dust cells in the sputa policemen and the rural population were 103.8 and 12.48, respectively (p < .0001). The numbers of dust cells were highest in policemen who smoked (relative risk = 3.95; p < .006). The mean numbers of siderocytes in policemen and the rural population were 0.99 and 5.31, respectively (not statistically significant, Mann-Whitney test). The difference between the number of subjects with hemosiderin-laden macrophages in traffic policemen and in the control group was small, but it was significant statistically (p < .004). In traffic policemen, it was related to smoking and time of exposure to air pollution, whereas in the control population it was related to heart-pulmonary diseases. In this study, we observed a synergistic effect between smoking and environmental pollution. In addition, less than 5 y of exposure can caused significantly increased (a) numbers of macrophages and (b) inflammatory infiltrate in sputa. The results of the cytological diagnosis revealed a statistically significant difference between policemen and the rural population (p < .001). The cytological exam of sputa and correlations with smoking within each population were not statistically significant. In conclusion, macrophage count in sputum is a sensitive and reproducible method for investigators to verify pulmonary changes that may be observed before they can be measured by functional tests.

Fine needle aspiration cytology of squamous cell carcinoma arising in a thyroglossal duct cyst : A case report

BACKGROUND Carcinoma arising in a thyroglossal duct cyst is a rare entity. Malignancy generally is revealed only after surgical excision of a thyroglossal duct lesion because of the lack of specific physical findings. CASE A 68-year-old male presented with a squamous cell carcinoma arising in a midline cyst in the neck. The malignancy had been discovered because of an enlarged metastasized lymph node in the left side of the neck. Fine needle aspiration cytology (FNA) showed cells with marked nuclear atypia and keratinizing cells. CONCLUSION To our knowledge, this is the 10th squamous cell carcinoma reported and, among these, the first case diagnosed preoperatively by FNA cytology. A firm diagnosis at the preoperative stage is important with this neoplasm to plan extensive surgical intervention.