Ezio Gallina

Interleukin-6 and acute-phase proteins in head and neck cancer

The acute-phase response is the answer of the organism to a disturbance of its homeostasis and is characterized by dramatic changes in the concentration of some plasma proteins defined as acute-phase proteins. In recent years several data have shown that interleukin-6 (IL-6) is the major inducer of acute-phase protein synthesis in human hepatocytes. Recently, we demonstrated higher IL-6 serum levels in head and neck cancer (HNC) patients than in healthy subjects. In the present study we examined the relationship between levels of IL-6 and of several acute-phase proteins, including C-reactive protein (CRP), α1-antitrypsin (AAT), αl-acid glycoprotein (AAG), haptoglobin (HPT) and fibrinogen. Eighteen patients were studied and had squamous cell carcinoma of the larynx (n = 9), oral cavity (n = 4), oropharynx (n = 3) and hypopharynx (n = 2). Proteins were measured at three time points before and three time points after surgery. Significant (P < 0.0001) relationships were found between IL-6 and CRP (r = 0.69), and fibrinogen (r = 0.51), whereas no correlation was found with AAT (r = 0.13, P = 0.56), AAG (r = 0.38; P = 0.07) and HPT (r = 0.16; P = 0.46). These data strongly suggest that IL-6 may play a key role in acute-phase protein synthesis in HNC and in regulation of the complex host response to malignancies.

Correlations between histopathological and biological findings in nasopharyngeal carcinoma and its prognostic significance.

Forty‐five consecutive cases of nasopharyngeal carcinoma were morphologically and immunocyto‐chemically studied using monoclonal (anti‐B and anti‐T cell) and polyclonal (anti‐SlOO protein and antilysozyme) antibodies with the peroxidase‐anti‐peroxidase method to identify infiltrating lymphocytes (T and B cell) and histiocytes (monocytic/mac‐rophagic and dendritic cells) in nasopharyngeal carcinoma.

Prognostic Significance of Accessory Cells and Lymphocytes in Nasopharyngeal Carcinoma

Forty-five consecutive biopsy specimens of nasopharyngeal carcinoma (NPC) and 10 biopsies of healthy nasopharyngeal mucosa obtained from non-cancer patients were investigated by immunohistochemical methods. Monoclonal (B2, T1) and policlonal antibodies (against S-100 protein and lysozyme) with reference to infiltrating lymphocytes and accessory cells (monocytic/macrophagic and dendritic cells) were used. Variable population densities of dendritic cells (S100+) were demonstrated in 22 out of the 45 cases (49%) of NPC; the distribution of these cells was typically within the cancer nests. Monocytic/macrophagic cells (Lys+) were found along the tumor margins and interspersed among the tumor cells in 14 out of 45 (31%) cases. No significant statistical correlation between density of accessory cells and histological type of NPC (classified according to Micheau criteria) was found. Cases with a moderate to marked density of dendritic and monocytic/macrophagic cells survived longer than those with a slight one (mean survival of 63%, 67% and 29%, 27% respectively). In NPC tissues T-lymphocyte infiltration was prevalent. In contrast, B cells were numerous and T cells rare in normal control tissues. The intensity of T-cell infiltration was significantly high in cases with a marked density of S-100+ cells, according to the ability of these cells to present antigens to sensitized T-cells. This study suggests a prognostic significance for reactive cells infiltrating NPC, which means longer survival for cases associated with marked infiltration density of accessory cells.

Detection of Epstein-Barr Virus Genome in Sinonasal Undifferentiated Carcinoma by Use of in Situ Hybridization

Associations between Epstein-Barr virus and undifferentiated carcinomas of nasopharynx, parotid gland, and thymus have recently been reported. Epstein-Barr virus has also been associated with malignant lymphoma of the nose and paranasal sinuses. These findings raise the possibility that Epstein-Barr virus may additionally be linked to undifferentiated carcinoma of the nose and paranasal sinuses (SNUC), an uncommon but distinctive and highly aggressive neoplasm. Histologically, SNUC consists of small and medium cells, the precise characterization of which often requires immunocytochemical analysis. This study investigates the presence of DNA sequences of Epstein-Barr virus in biopsy specimens of 13 cases of SNUC that were defined immunocytochemically by use of previously reported criteria. In situ hybridization was used to detect Epstein-Barr virus genome in different cell types in routinely processed, paraffin-embedded tissues. Epstein-Barr virus-specific DNA sequences were detected in tumor cells of SNUC specimens from 5 of the 13 cases examined. No correlation was found between positive hybridization and primary tumor site, morphologic subtype, or disease course. Epstein-Barr virus DNA was detected in 38% (5 of 13) of the SNUC samples analyzed. This finding suggests that this virus may play a role in the pathogenesis of this rare neoplasm.

Interleukin-1 beta and interleukin-6 release by peripheral blood monocytes in head and neck cancer.

In patients with advanced head and neck squamous cell carcinoma (HNSC), evidence of cell-mediated immunity and monocyte functional abnormalities has been reported. We studied the production of interleukin 1 beta (IL-1 beta) and interleukin 6 (IL-6) by peripheral blood monocytes from 22 patients with HNSC (12 larynx and ten oral cavity cancers) in comparison with monocyte cytokine production of age-matched healthy subjects. Pure monocytes were incubated with and without lipopolysaccharides (LPS) (10 micrograms ml-1) for 4 h at 37 degrees C and IL-1 beta and IL-6 concentrations were determined in supernatants by specific ELISA. There was no significant difference in IL-1 beta levels in monocyte supernatants from cancer in comparison to control subjects; conversely, a higher IL-6 production by unstimulated and LPS-activated cells from HNSC patients than from controls was found. No relationship was observed between cytokine production and cancer stage. The regression analysis evidenced a significant correlation between IL-1 beta and IL-6 monocyte-release in HNSC patients and in controls, so suggesting a possible autocrine control of IL-6 production by other cytokines.

Prostaglandins in squamous cell carcinoma of the larynx: tumor and peritumor synthesis.

Prostaglandin (PG) E2, 6ketoPGF1 alpha and Thromboxane B2 (TxB2) production by the tumor, peritumor and control tissue were investigated in specimens from patients (n = 11) with squamous cell carcinoma of the larynx, in relation to the extension and infiltration of the neoplasm and to the presence of inflammation, fibrosis and necrosis. In all specimens detectable amounts of 6ketoPGF1+ and TxB2 were found, but the predominant metabolite was PGE2. No differences in the levels of TxB2 and 6ketoPGF1 alpha were observed, but the only patient with lymphnodal involvement showed the lowest levels of 6ketoPGF1 alpha both in tumor and peritumor tissue. Higher amounts (p less than 0.05) of PGE2 were synthesized by peritumor tissues in comparison to control mucosa and tumor tissue independently of the occurrence of reactive infiltration. PGs synthesis did not correlate with inflammation, fibrosis, necrosis or staging of the neoplasm. However the two cases in stage T4 showed PGE2 generation at the highest levels both in neoplastic and perineoplastic tissue. These findings indicate that in squamous cell carcinoma of the larynx an increased production of PGE2 occurs, stemming not only from inflammatory cells but at least in part from neoplastic cells. This suggests that the study of arachidonic acid metabolism may contribute to characterization of the primary cancer and lead to better understanding of the mechanisms of tumor growth and diffusion.

Monocyte Tumor Necrosis Factor Production in Head and Neck Squamous Cell Carcinoma

Changes in monocyte and macrophage function have been demonstrated in patients with head and neck squamous cell carcinoma. The purpose of this study was to evaluate tumor necrosis factor (TNT) production by activated monocytes from patients with head and neck squamous cell carcinoma and to evaluate its relation to cancer stage, weight loss, and performance status. Monocytes from patients (n = 10) and controls (n = 10) were isolated from peripheral blood mononuclear cells by plastic adherence and incubated with lipopolysaccharide (10 μg/mL). The TNF concentration of supernatants was assayed by TNFα‐specific immunoassay. The TNF production by monocytes from head and neck squamous cell carcinoma patients was significantly higher (P<.001) than those of controls. No significant relationship was found to cancer stage, weight loss, and performance status. These findings indicate that, in head and neck squamous cell carcinoma patients, an increased TNF production by activated monocytes takes place which does not correlate with cancer stage, cancer‐related weight loss, and performance status.

T Lymphocytes from tonsil and peripheral blood show different cytolytic and helper activities

T lymphocytes from tonsil (To) and peripheral blood (PB) of 4 tonsillectomized children were subjected to clonal expansion with PHA in order to analyze at single cell level their cytolytic activity and their ability to produce interleukins such as IL-2, IFN-gamma and IL-4. Analyzing all T-cell clones (CD4+ and CD8+) obtained from To in comparison with those from PB, a reduced proportion of cells with lectin-dependent cytolytic activity (LDCC) (25% vs. 42%, p less than 0.01) and natural killer (NK) activity (18% vs. 31%, p less than 0.02) was found. These differences were proportionally related to the lower number of CD8+ T-cells in To than in PB. The proportion of CD4+ clones able to produce IL-2 and/or IL-4 were higher in To (75% and 61%) than in PB (52% and 25%, p less than 0.001 and p less than 0.001, respectively). In contrast, the proportion of CD4+ clones able to produce IFN-gamma was similar (53% and 58%) in both series of clones. According to the patterns of lymphokine synthesis, tonsillar T-cells differed from PB T-cells as follows: 1) the number of Th1-like CD4+ clones producing IL-2 and/or IFN-gamma (but not IL-4) were 23% vs. 44% in PB (p less than 0.001); 2) there was no difference between To and PB in the proportion of CD4+ clones producing IL-4 alone (Th2 clones: 9% vs. 8%); 3) CD4+ clones synthesizing IL-2, IL-4 and IFN-gamma at the same time were more frequent in To than in PB (Th3 clones: 53% vs. 17%, p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Cerebrospinal Fluid Rhinorrhea and Unilateral Nasal Polyposis: A Case Report

We report a case of cerebrospinal fluid (CSF) rhinorrhea and unilateral polyposis in a 53-year-old woman. The clinical features, tomograms, and CT scan with Metrizamide infusion are examined. The analysis of this case evidences that: 1) A CSF can occur also after a long time (3 years) following a head injury; 2) CT cisternography with Metrizamide can demonstrate a leakage, but not always the fluid egress from the intracranial cavity; and 3) A CSF rhinorrhea may be the primary cause and not an occasional association or complication of a reactive phlogistic nasal disease.