[Study on the value of systemic immune inflammation index and nomogram in predicting the prognosis of patients with mucoepidermoid carcinoma].

PURPOSE: To investigate the relationship between preoperative systemic immune-inflammation index (SII) and relapse-free survival (RFS) after surgical resection of mucoepidermoid carcinoma(MEC). METHODS: The data of 135 patients with MEC who underwent surgical resection in the First Affiliated Hospital of Zhengzhou University from January 2016 to July 2019 were collected, and the receiver operating characteristic(ROC) curve was performed on the SII of patients. The optimal cut-off value was obtained by ROC analysis. Therefore, the patients' SII index was divided into high and low group, and survival analysis was performed by Kaplan-Meier method. Cox proportional regression model and least absolute shrinkage and selection operator (LASSO) were used to analyze the factors influencing prognosis, and a nomogram model was built to predict patients' relapse-free survival(RFS). Area under curve (AUC) and correction curve were used to evaluate the model and verify the consistency. RESULTS: Survival analysis showed that the RFS rate in low SII group was significantly higher than that in high SII group. Cox proportional hazard regression model showed high SII(HR=2.179, 95%CI: 1.072-4.426, P=0.031) and low tumor differentiation(HR=6.894, 95%CI: 2.770-17.158, P=0.000) and cervical lymph node metastasis (HR=2.091, 95%CI: 1.034-4.230, P=0.040) were significant predictors of poor RFS. CONCLUSIONS: The lower the preoperative SII, the better the prognosis of patients. The nomogram prognosis of MEC based on SII is effective.

Primary cutaneous mucoepidermal carcinoma.

Mucoepidermal carcinoma (MEC) is a tumour having mixed components of mucus secreting and epidermoid cells. Salivary glands are the the most common site of origin. Primary cutaneous MEC is a rare presentation. We report a primary cutaneous MEC in a 98-year-old woman presenting a noduloulcerative lesion over the dorsum of the nose. Histopathology of the tumour showed nests of epidermoid cells with glandular differentiation and mucin production. The diagnosis was confirmed by immunohistochemistry.

Parotid sclerosing mucoepidermoid carcinoma: a case report and immunohistochemical study.

Here we report the case of a 63-year-old female with a parotid sclerosing mucoepidermoid carcinoma diagnosed and treated at the Department of Oral and Maxillofacial Surgery, Emergency County Hospital of Craiova, Romania. The clinical and imaging investigation revealed a parotid malignant tumor with central fluid-filled cystic formation. Histopathology found an intermediate grade sclerosing mucoepidermoid carcinoma that invaded the adjacent adipose and striated muscle tissues, but without perineural and lymphovascular invasion. The immunohistochemistry investigated mainly biomarkers involved in the induction of a local aggressive behavior. This case report describes a rare parotid sclerosing mucoepidermoid carcinoma with peculiar clinical and morphological characteristic features. The immunohistochemical study sustained its intermediate grade malignancy highlighting the prognostic value of some of the used biomarkers.

Immunoprofile of c-MET/PI3K signaling in human salivary gland tumors.

OBJECTIVE: The aim of this study was to analyze the expression pattern of proteins in the HGF/c-MET/PI3K signaling pathway in salivary gland tumors (SGTs) and to correlate the findings with the proliferative index and clinical parameters. STUDY DESIGN: We assembled tissue microarrays (TMAs) of 108 cases of SGTs, including 69 cases of pleomorphic adenoma (PA), 24 cases of adenoid cystic carcinoma (AdCC), and 15 cases of mucoepidermoid carcinoma (MEC). An immunohistochemical analysis of hepatocyte growth factor (HGF), MET phosphorylation (p-MET), protein kinase B (AKT) phosphorylation (p-AKT), and Ki-67 proteins was performed. RESULTS: Benign and malignant SGTs presented similar scores of HGF-positive cells (P = .36), whereas, malignant SGTs exhibited higher levels of p-MET (P = .001) and p-AKT (P = .001) than benign SGTs. No correlation of HGF, p-MET, or p-AKT expression was observed with clinical parameters. PA had a lower proliferative index than either AdCC (P = .001) or MEC (P = .001). CONCLUSIONS: The salivary gland carcinomas exhibited increased activation of the HGF pathway, as evidenced by the phosphorylation of the MET receptor, and increased activation of the PI3K pathway, as indicated by p-AKT. These data suggest that the HGF/c-MET/PI3K signaling pathway is active in SGTs, especially in malignant neoplasms.

Postoperative abnormal response of C-reactive protein as an indicator for infectious complications after oral oncologic surgery with primary reconstruction.

BACKGROUND: C-reactive protein (CRP) screening has been reported to be reliable for detection of infectious complications. Postoperative abnormal response of CRP can predict wound infection in colorectal surgery. This study aimed to determine the efficacy of CRP monitoring to detect infectious complications in oral oncologic surgery. METHODS: One hundred patients who underwent oral cancer resection with primary reconstruction were enrolled. Postoperative kinetics of CRP were classified into a normal or abnormal response. RESULTS: A normal CRP response after surgery was observed in 61 patients and an abnormal response was observed in 39. There were postoperative infectious complications in 21 patients, with surgical site infections in 13 patients (early onset in six and late onset in seven). Non-wound infections were found in nine patients. Sensitivity, specificity, the positive predictive value, and the negative predictive value for abnormal CRP response as a predictor for early infectious complications were 100%, 70.1%, 35.9%, and 100%, respectively. CONCLUSION: Postoperative serial CRP screening is a useful test as an indicator of infectious complications in oral oncologic surgery. Normal CRP responses can rule out almost all early infectious complications.

Sclerosing mucoepidermoid carcinoma with eosinophilia of the salivary gland: case report and review of the literature.

Sclerosing mucoepidermoid carcinoma with eosinophilia (SMCE) of the salivary gland is a rare variant of mucoepidermoid carcinoma. We report a case of SMCE in the right submandibular gland of a 79-year-old man. Fine needle aspiration cytology revealed cohesive clusters of atypical squamous epithelial cells admixed with cells containing intracytoplasmic mucin and eosinophils. Histologically, the tumor was composed of epithelial nests with keratinizing cells occasionally present at the center, as well as peripherally located atypical basaloid cells, and some mucin-containing cells embedded in a fibrosclerotic stroma, which were accompanied by a prominent lymphoplasmacytic and eosinophilic infiltrate. Inflammatory infiltrate and stromal fibrosclerosis also were seen in the non-neoplastic salivary gland tissue adjacent to the tumor. Immunohistochemically, many plasma cells were IgG4-positive. The postoperative serum IgG4 level was elevated. Our reverse transcription-polymerase chain reaction using formalin-fixed, paraffin-embedded tumor tissue failed to detect any fusion-gene transcripts which are specifically identified in ordinary mucoepidermoid carcinoma. The findings of the present case suggest that this rare type of salivary gland carcinoma may be associated with a chronic inflammatory condition such as IgG4-related sclerosing disease. Only 23 cases of sclerosing mucoepidermoid carcinoma with or without eosinophilic infiltratie have been reported to date in such an anatomical location.

IgG4(+) plasma cells in sclerosing variant of mucoepidermoid carcinoma.

IgG4-related sclerosing disease is a recently described syndrome with unique histologic features characterized by intense lymphoplasmacytic infiltrates with increased IgG4 plasma cells and dense stromal sclerosis. The disease spectrum frequently includes benign inflammatory diseases, such as autoimmune pancreatitis, cholangitis, and chronic sclerosing sialadenitis (CSS). Mucoepidermoid carcinoma (MEC) is the most common primary malignancy in the salivary gland. The rare sclerosing variant of MEC is characterized by dense stromal sclerosis and lymphoplasmacytic infiltrates. Our goal was to further characterize lymphoplasmacytic infiltrates with respect to IgG4 expression. Six sclerosing MECs from our pathology service over the past 20 years were selected. In addition, 11 regular MECs with lymphoplasmacytic infiltrates, 4 CSS cases, and 12 nonsclerosing chronic sialadenitis cases were evaluated. None of the sclerosing MEC patients had IgG4-related sclerosing disease. The absolute number of IgG4 plasma cells was significantly increased in sclerosing MEC as compared with the regular type (75 vs. 20 per image field; P<0.05). Furthermore, the proportion of IgG4/IgG plasma cells was markedly elevated in sclerosing MEC as compared with the regular type (46.5% vs. 17%; P<0.05). In CSS, IgG4/IgG ratio was significantly increased as compared with nonsclerosing chronic sialadenitis (54% vs. 6.73%; P<0.01). This study is the first to demonstrate increased IgG4 plasma cells in sclerosing MEC. The association of elevated IgG4 plasma cells with increased fibrosis in the sclerosing variant of MEC suggests a role of IgG4 plasma cells in fibrogenesis and may be a new concept related to sclerosis in cancer.

MUC5AC expression through bidirectional communication of Notch and epidermal growth factor receptor pathways.

Hyperproduction of goblet cells and mucin in the airway epithelium is an important feature of airway inflammatory diseases. We investigated the involvement of Notch signaling in MUC5AC expression in NCI-H292 cells, a human lung carcinoma cell line. Epidermal growth factor (EGF) stimulated generation of the Notch intracellular domain (NICD) in a RBP-Jκ-dependent manner. Treatment with γ-secretase inhibitors L-685,458 or DAPT or introduction of small interfering RNA directed against Notch1 reduced EGF-induced MUC5AC expression. The inhibitory effect of L-685,458 on EGF-induced MUC5AC mRNA and protein expression was also observed in primary human bronchial epithelial cells. Blockage of Notch signaling with L-685,458 or Notch siRNA resulted in a decrease in EGF-induced phosphorylation of ERK. These results suggested that ERK activation is necessary for the regulation of EGF receptor (EGFR)-mediated MUC5AC expression by Notch signaling. Conversely, forced expression of NICD induced both EGFR and ERK phosphorylation with MUC5AC expression even in the absence of EGF. Treatment of the NICD-expressing cells with EGF further augmented ERK phosphorylation in an additive manner. The ERK phosphorylation induced by exogenous NICD was inhibited by treatment with an Ab that antagonizes EGFR activity as well as by inhibitors of EGFR and ERK, implying that Notch signaling induces MUC5AC expression by activating the EGFR pathway. Collectively, these results suggest that MUC5AC expression is regulated by a bidirectional circuit between Notch and EGFR signaling pathways.

CCL20/CCR6 feedback exaggerates epidermal growth factor receptor-dependent MUC5AC mucin production in human airway epithelial (NCI-H292) cells.

Mucous hypersecretion is an important feature of obstructive airway diseases such as asthma, chronic obstructive pulmonary disease, and cystic fibrosis. Multiple stimuli induce mucin production via activation of an epidermal growth factor receptor (EGFR) cascade, but the mechanisms that exaggerate mucin production in obstructive airway diseases remain unknown. In this study, we show that binding of CCL20, a G protein-coupled receptor (GPCR) ligand that is upregulated in the airways of subjects with obstructive airway diseases, to its unique GPCR CCR6 induces MUC5AC mucin production in human airway epithelial (NCI-H292) cells via metalloprotease TNF-α-converting enzyme (TACE)-dependent EGFR activation. We also show that EGFR activation by its potent ligand TGF-α induces reactivation of EGFR via binding of endogenously produced CCL20 to its receptor CCR6 in NCI-H292 cells but not in normal human bronchial epithelial (NHBE) cells, exaggerating mucin production in the NCI-H292 cells. In NCI-H292 cells, TGF-α stimulation induced two phases of EGFR phosphorylation (EGFR-P). The second EGFR-P was TACE-dependent and was responsible for most of the total mucin induced by TGF-α. Binding of endogenously produced CCL20 to CCR6 increased the second EGFR-P and subsequent mucin production induced by TGF-α. In NHBE cells, TGF-α-induced EGFR activation did not lead to significant CCL20 production or to EGFR rephosphorylation, and less mucin was produced. We conclude that NCI-H292 cells but not NHBE cells produce CCL20 in response to EGFR activation, which leads to a second phase of EGFR-P and subsequent exaggerated mucin production. These findings have potentially important therapeutic implications in obstructive airway diseases.

Extracellular matrix metalloproteinase inducer expression in salivary gland tumors: a correlation with microvessel density.

The purpose of this study was to investigate the expression pattern of extracellular matrix metalloproteinase inducer (EMMPRIN) as well as the correlation between EMMPRIN and microvessel density (MVD) in salivary gland tumors. Extracellular matrix metalloproteinase inducer expression and MVD were examined immunohistochemically on paraffin-embedded tissue specimens from 95 patients with salivary gland tumors, who underwent surgical resection from 1998 to 2006. Reverse transcription-polymerase chain reaction was used to monitor EMMPRIN mRNA expression in frozen samples. Extracellular matrix metalloproteinase inducer expression in mucoepidermoid carcinomas and adenoid cystic carcinomas was significantly higher than in normal salivary gland tissues and pleomorphic adenomas (P < 0.05). The MVD of mucoepidermoid carcinomas and adenoid cystic carcinomas was significantly higher compared with pleomorphic adenomas (P < 0.05). The MVD of the EMMPRIN-positive expression group was significantly higher than the MVD of the EMMPRIN-negative expression group (P < 0.05). Extracellular matrix metalloproteinase inducer mRNA expression in malignant salivary gland tumors was higher than that in pleomorphic adenomas (P < 0.05). This study suggests that EMMPRIN expression is an important feature of malignant salivary gland tumors and can be used as a biologic marker to characterize salivary gland tumors. Extracellular matrix metalloproteinase inducer is also a positive angiogenic factor in salivary gland tumors.

Glucose transporter protein 1 expression in mucoepidermoid carcinoma of salivary gland: correlation with grade of malignancy.

Mucoepidermoid carcinoma (MEC), the most common primary salivary malignancy, shows great variability in clinical behaviour, thus demanding investigation to identify of prognostic markers. Since Warburg's studies, unrestricted cell growth during tumorigenesis has been linked to altered metabolism, implying hypoxic stimulation of glycolysis and diminished contribution of mitochondrial oxidative phosphorylation to cellular ATP supply. Hypothesizing that the study of MEC metabolic status could lead to the discovery of prognostic markers, we investigated by immunohistochemistry the expression of glucose transporter 1 (Glut-1), mitochondrial antigen and peroxiredoxin I (Prx I) in samples of MEC from different histological grades. Our results showed that mitochondrial antigen and Prx I were expressed in the majority of the MEC cases independent of the histological grade. In contrast Glut-1 expression increased significantly as the tumours became more aggressive. These results suggested that oxidative phosphorylation may contribute to ATP supply in all stages of MEC progression, and that the relative contribution of glycolysis over mitochondria for cellular ATP supply increases during MEC progression, favouring growth under low oxygen concentration. In addition, the observed high Prx I protein levels could provide protection to tumour cells against reactive oxygen species generated as a consequence of mitochondrial function and hypoxia-reoxygenation cycling. Altogether our findings suggest that upregulation of Glut-1 and Prx I constitute successful adaptive strategies of MEC cells conferring a growth advantage over normal salivary gland cells in the unstable oxygenation tumour environment.

Morphometric analysis of CD34-positive vessels in salivary gland adenoid cystic and mucoepidermoid carcinomas.

BACKGROUND: Carcinomas of the salivary glands are uncommon and morphologically a diverse group of malignancies. To evaluate the prognostic value of CD34 immunostaining of the vessels in adenoid cystic carcinoma (AdCC) and mucoepidermoid carcinoma (MEC), an automated image analysis method was used. METHOD: In a nationwide study, covering salivary gland cancer (SGC) patients in Finland 1991-1996, 37 AdCC and 18 MEC patients (M 25, F 30, age 25-90, mean 63) were included. In addition to clinical characteristics the size, shape, staining intensity and vessel density in CD34 immunostained histologic samples were measured. RESULTS: Altogether 4433 vessels were measured from AdCC and 2615 from MEC tumor. Of the total tumor vessels measured, 2651 were from patients who deceased with disease (Group I) and 4397 were from specimens derived from those who did not die of disease (Group II) during the 10-year follow-up. The staining intensity was significantly higher in MEC than in AdCC tumor (P = 0.0005). In MEC, the Group I patients had a higher staining intensity among high-grade patients compared with patients with low grade disease, whereas the tumors in Group II had a lower staining intensity among the high-grade compared with the low grade tumors (P = 0.018). A higher vessel density was found in patients with MEC in group II compared with group I (P = 0.017). CONCLUSIONS: The staining intensity of CD34 positive vessels in MEC was higher than in AdCC. In MEC, higher staining intensity of vessels in high-grade tumors and lower vessel density in all MEC patients, predicted poor survival.

Cyclooxygenase-2 regulates the degree of apoptosis by modulating bcl-2 protein in pleomorphic adenoma and mucoepidermoid carcinoma of the parotid gland.

CONCLUSION: These results suggest that COX-2 and bcl-2 protein were overexpressed and that apoptosis was reduced in MEC compared to PMA, and that COX-2 may regulate the degree of apoptosis by modulating bcl-2 protein in PMA and MEC. OBJECTIVE: Cyclooxygenase (COX)-2 plays a crucial role in tumorigenesis and overexpression of COX-2 in vitro accompanied by overexpression of bcl-2 protein has been shown to reduce apoptosis. The purpose of this study was to verify that COX-2 regulates the degree of apoptosis by modulating bcl-2 protein in benign and malignant parotid gland tumors. : We examined archival formalin-fixed, paraffin-embedded tissue sections of 10 pleomorphic adenomas (PMAs) and 10 mucoepidermoid carcinomas (MECs) by immunostaining with anti-COX-2, anti-bcl-2 and anti-single-stranded DNA (ssDNA) antibodies. Labeling indices of the three antibodies were calculated using computer-assisted image analysis. RESULTS: Labeling indices (mean+/-SD) of anti-COX-2 antibody in PMA and MEC were 2.05+/-1.30 and 11.2+/-2.95, respectively (p < 0.001), those of anti-bcl-2 antibody were 2.00+/-1.28 and 9.68+/-4.05, respectively (p < 0.001) and those of anti-ssDNA antibody were 8.06+/-2.54 and 2.08+/-1.47; respectively (p <0.001). Correlation coefficients between the labeling indices of anti-COX-2 antibody and anti-bcl-2 antibody, anti-bcl-2 antibody and anti-ssDNA antibody and anti-COX-2 antibody and anti-ssDNA antibody were 0.88, -0.75 and -0.76, respectively (p <0.001).

[Detection of P-glycoprotein and glutathine S-transferase in mucoepidermoid carcinoma of salivary gland].

OBJECTIVE: The aim of this study was to investigate the mechanism(MDR) of multidrug resistance(MDR) of mucoepidermoid carcinoma in salivary gland. METHODS: 40 cases of mucoepidermoid carcinoma in salivary gland were examined the MDR gene product P-glycoprotein using a monoclonal antibody JSB-1. And 10 of them were also investigated by detecting the expression of GST-pi. All the cases had not been accepted any therapy before the samples were collected. RESULTS: 1. Positive expression of JSB-1 was observed in 27 of the 40 specimens. The positive expression was related not only with clinical stage, but also with differentiation degree. 2. The GST-pi positive expression was found in 9 of 10 cases. There was no significant different between the positive expression of JSB-1 and GST-pi. CONCLUSION: JSB-1 and GST-pi play an important role in MDR of mucoepidermoid carcinoma.

MUC4 and ERBB2 expression in major and minor salivary gland mucoepidermoid carcinoma.

BACKGROUND: Peptide sequence homology between the gene product of human MUC4 and rat sialomucin complex (SMC) has recently been reported. Each contains a mucin subunit with antiadhesive activity linked to the plasma membrane by means of a transmembrane subunit with two epidermal growth factor (EGF)-like domains that act as ligand for ErbB2. This study investigates MUC4 and ErbB2 receptor expression in major and minor salivary gland mucoepidermoid carcinoma and correlates patterns of expression with clinical outcomes. METHODS: MUC4 antigens and ErbB2 receptor expression are localized by immunohistochemical studies that use archival formalin-fixed and paraffin-embedded tissue. Clinical outcomes are determined by retrospective chart review of all patients (n = 28) with available archived pathologic specimens at the University of Miami-affiliated hospitals treated between 1994 and 2000. RESULTS: Median survival time was 24 months (range, 2-60 months) among the nine patients who died, whereas median follow-up time in the remaining 19 patients is 33.4 months (range, 4.7-73 months). A trend toward a reduction in MUC4 antigen expression in high-grade tumors (55% expression) compared with low-grade (91% expression) and intermediate-grade (100% expression) tumors is identified (chi square, p =.0975). Patients with tumors expressing MUC4 antigens are at reduced risk of death (hazard ratio [HR], 0.20; p =.0531). Adjustment for pathologic grade, T stage, and age results in a much higher risk of death for patients whose tumors do not express MUC4 antigens, although this does not meet statistical significance (HR, 26.6; p =.1). Analysis of recurrence adjusting for T stage reveals that patients whose tumors do not express MUC4 antigens are at increased risk of recurrence compared with patients whose tumor expresses MUC4 antigens (HR, 6.37; p =.03). ErbB2 receptor staining is noted in seven of 28 patients, with five of these seven showing 2+ and 3+ membrane-staining patterns. Adjustment for pathologic grade and age suggests that patients whose tumors express high levels of ErbB2 (2+, 3+) are at increased risk of death compared with patients with low or no expression of ErbB2 (HR, 2.29; p =.32). MUC4 antigen positivity is seen in two of the five cases with 2+ and 3+ staining for ErbB2. CONCLUSIONS.: These findings suggest MUC4 antigen positivity is associated with reduced risk of death and reduced risk of recurrence and may identify a subset of patients with more favorable prognosis. Although limited by small sample size, analysis reveals ErbB2 overexpression is not consistently associated with MUC4 antigen positivity and might be associated with increased risk of death.

Human alpha-and beta-defensin immunoreactivity in oral mucoepidermoid carcinomas.

The purpose of this study was to demonstrate the immunohistochemical localization and distribution of human alpha- and beta-defensins, peptides with antimicrobial activity, in oral mucoepidermoid carcinoma tissue. Tissue samples were embedded in paraffin and alpha- and beta-defensins were immunostained by the streptavidin-biotin coupled peroxidase method. Cancer cells that constituted the ducts, as well as neutrophils, were positively immunostained with the anti-alpha-defensin antibody (HNPs). On the other hand, epidermoid cells and intermediate cells were intensely stained with the anti-beta-defensin-2 (HBD-2) antibody. Mucous-secreting cells were clearly not immunostained with the anti-HBD-2 antibody. The epithelial hyperplasia region adjacent to the tumor tissues was also positively immunostained with the anti-HBD-2 antibody.

Mucoepidermoid carcinoma of the anal canal: an immunohistochemical study.

We present a case of mucoepidermoid carcinoma of the anal canal, with special reference to immunohistochemical analysis of the tumor to clarify its histogenesis. A 36-year-old man underwent surgery for mucoepidermoid carcinoma of the anal canal. Immunohistochemical analysis of the resected specimen was performed. Serial sections were stained immunohistochemically by the labeled streptavidin-biotin peroxidase method for various antigens, including epithelial membrane antigen (EMA); carcinoembryonic antigen (CEA); different types of cytokeratins, including CK10 and CAM 5.2; and p53 oncoprotein. The solid component of the tumor cells was immunohistochemically positive for EMA, CEA, and CAM 5.2, but negative for CK10. These staining patterns were different from those of anal squamous epithelium. These results confirm that mucoepidermoid carcinoma of the anus may arise from the anal transitional zone, and that it is biologically different from squamous cell carcinoma of the anus.

Comparison of integrin alpha chain expression in benign and malignant salivary gland tumors.

OBJECTIVE: This study investigates the distribution of the alpha chain of the integrin family of extracellular matrix receptors in a series of adenomas and carcinomas of salivary gland origin to determine if the malignant phenotype is associated with modification of the expression of these receptors. STUDY DESIGN: Cryostat sections of 36 tumor specimens were stained by a standard streptavidin-biotin-peroxidase technique using primary monoclonal antibodies against alpha 1-6 and alpha v integrin chains. The immunohistochemical reaction was scored using a three-point scale and the results were analyzed using Fisher's exact test. RESULTS: In salivary adenomas, alpha 2, alpha 3, alpha 4, alpha 6, and alpha v chains were widely expressed in most of the cases studied. The alpha 1 subunit was prominently expressed by the epithelial cells of Warthin's tumor, whereas a minority of pleomorphic adenomas showed immunoreactivity for this antigen. We observed alpha 5 subunit expression only in the mesenchymal-like component of pleomorphic adenomas. In salivary carcinomas, integrin alpha chain expression was heterogeneous, varying greatly between different histotypes and within the same histotype. The distribution of the antigens was similar to that of adenomas, except for the alpha 6 chain, which localized not only at the interface between cell and matrix, but also at sites of cell-cell contact. When the immunohistochemical levels of integrin alpha chain expression were compared in adenomas and carcinomas, expression significantly decreased for the alpha 6 and alpha v chains (p = 0.0007; p = 0.002, respectively). CONCLUSIONS: Loss of alpha 6 and alpha v integrin subunits occurring in salivary gland carcinomas could modify the adhesive properties of malignant cells, contributing to the invasive potential of these tumors.

Mast cell tryptase is a mitogen for epithelial cells. Stimulation of IL-8 production and intercellular adhesion molecule-1 expression.

Tryptase, a protease unique to the mast cell secretory granule, is released in substantial quantities into the respiratory tract of patients with inflammatory disease of the airways. We have investigated the potential of tryptase to act as a mitogen for bronchial epithelial cells and to stimulate release of IL-8 and expression of ICAM-1. Tryptase was isolated from extracts of human lung tissue using ammonium sulphate precipitation, octyl agarose, and heparin agarose chromatography. Purified tryptase stimulated DNA synthesis in the human epithelial cell line H292, as measured by [3H] thymidine incorporation. Maximal growth was observed after 24 h using 25 mU/ml of tryptase (where 1 micron is defined as that which can hydrolyze 1 mumol of the peptide substrate N-alpha-benzoyl-DL-arginine p-nitroanilide hydrochloride per minute at 25 degrees C), a concentration that is likely to be achieved in vivo. Inhibitors of tryptase activity, including leupeptin and benzamidine hydrochloride, significantly decreased tryptase-induced stimulation of DNA synthesis, indicating the requirement for an active catalytic site. Tryptase stimulated a catalytic site-dependent release of IL-8 from epithelial cells after 24 h, and this was associated with up-regulation of ICAM-1 expression, as revealed by FACS analysis. Tryptase may play a critical role in epithelial repair and in the recruitment of granulocytes following mast cell activation.

Leukemoid reaction resulting from multiple cytokine production in metastatic mucoepidermoid carcinoma with central necrosis.

We report a male patient with metastatic high-grade mucoepidermoid carcinoma and associated leukemoid reaction. The patient was transferred to our hospital due to persistent spiking fever, marked granulocytosis, and suspected liver abscess. After thorough bacteriological studies, including cultures of blood and material aspirated from the "liver abscess", no evidence of infection was documented. The patient suffered from persistent spiking fever for more than 4 weeks in spite of empirical antibiotic treatment, and repeated aspiration of the presupposed liver abscess. He underwent exploratory laparotomy for intended surgical evacuation of the liver abscess and bacteriological diagnosis. The operative findings were compatible with metastatic carcinoma with multiple liver and retroperitoneal lymph node involvement and tumor necrosis. The pathology report indicated high-grade mucoepidermoid carcinoma. Immunohistochemistry showed positive staining for interleukin-1 alpha (IL-1 alpha) and IL-6. Elevation of cytokine levels in the necrotic tumor fluid, including IL-1 alpha, IL-6, granulocyte-macrophage colony-stimulating factor and granulocyte colony-stimulating factor was confirmed by ELISA test. This case shows that multiple cytokine production from a metastatic tumor and its central necrotic area in the liver can produce a febrile leukemoid reaction mimicking a pyogenic liver abscess.