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Objective: To disclose the relationship between the expression of p16, p53 and nm23 and the significant morphologic characteristics in mucoepidermoid carcinoma., Methods: The proteins and mRNA in paraffin blocks from 41 mucoepidermoid carcinoma patients were studied with immunohistochemical methods and in situ hybridization respectively., Results: The negative expression of p16 was found in 62.5% (15/24) of the low differentiation grade and in 29.4% (5/17) of the high differentiation grade (P = 0.037). The positive p53 expression was detected in 70.8% (17/24) of the low grade neoplasms and in 23.5% (4/17) of the high grade (P = 0.003), while positive nm23 protein was present in 37.5% (9/24) and 64.7% (11/17) respectively (P = 0.086). However, no relationship was found between positive mRNA of p16, p53, nm23 and WHO pathologic grade., Conclusions: There is a significant correlation between expression of p16 and p53 and WHO pathologic grade of mucoepidermoid carcinoma, which indicates clinical prognostic significance. No correlation is noticed between the pathologic grade and the expression of nm23 protein and mRNAs of p16, p53 and nm23.

We sought to review our experience with salivary mucoepidermoid carcinoma (MEC) over two decades to confirm the validity and reproducibility of histologic grading and to investigate MIB-1 index as a prognosticator. Diagnosis was confirmed on 80 cases, and chart review or patient contact was achieved for 48 patients, with follow-up from 5 to 240 months (median 36 months). Immunohistochemistry with citrate antigen retrieval for MIB-1 was performed on a subset of cases. Kaplan-Meier survival curves were generated for each stage, site, and grade according to our proposed grading system. To address the issue of grading reproducibility, 20 slides were circulated among five observers, without prior discussion; slides were categorized as low-, intermediate-, or high-grade according to one's "own" criteria, and then according to the AFIP criteria proposed by Goode et al.10 Weighted kappa (kappa) estimates were obtained to describe the extent of agreement between pairs of rating. The Wilcoxon signed rank test or the Friedman test as appropriate tested variation across ratings. There was no gender predominance and a wide age range (15-86 years, median 49 years). The two most common sites were parotid and palate. All grade 1 MECs presented as Stage I tumors, and no failures were seen for this category. The local disease failure rates at 75 months for grades 2 and 3 MEC were 30% and 70%, respectively. Tumor grade, stage, and negative margin status all correlated with disease-free survival (DFS) (p = 0.0091, 0.0002, and 0.048, respectively). The MIB index was not found to be predictive of grade. Regarding the reproducibility of grading, the interobserver variation for pathologists using their "own" grading, as expressed by the kappa value, ranged from good agreement (kappa = 0.79) to poor (kappa = 0.27) (average kappa = 0.49). A somewhat better interobserver reproducibility was achieved when the pathologists utilized the standardized AFIP criteria (average kappa = 0.61, range 0.38-0.77). This greater agreement was also reflected in the Friedman test (statistical testing of intraobserver equality), which indicated significant differences in using one's own grading systems (p = 0.0001) but not in applying the AFIP "standardized" grading (p = 0.33). When one's own grading was compared with the AFIP grading, there were 100 pairs of grading "events," with 46 disagreements/100 pairs. For 98% of disagreements, the AFIP grading "downgraded" tumors. This led us to reanalyze a subset of 31 patients for DFS versus grade, for our grading schema compared with the AFIP grading. Although statistical significance was not achieved for this subset, the log rank value revealed a trend for our grading (p = 0.0993) compared with the Goode schema (p = 0.2493). This clinicopathologic analysis confirms the predictive value of tumor staging and three-tiered histologic grading. Our grading exercise confirms that there is significant grading disparity for MEC, even among experienced ENT/oral pathologists. The improved reproducibility obtained when the weighted AFIP criteria were used speaks to the need for an accepted and easily reproducible system. However, these proposed criteria have a tendency to downgrade MEC. Therefore, the addition of other criteria (such as vascular invasion, pattern of tumor infiltration [i.e., small islands and individual cells vs cohesive islands]) is necessary. We propose a modified grading schema, which enhances predictability and provides much needed reproducibility.

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.

Background: p27(Kip1), a cyclin-dependent kinase inhibitor, negatively regulates the G1 phase progression of the cell cycle by binding to the cyclin E/cyclin-dependent kinase 2 complex. This study was done to investigate the expression of p27(Kip1) in mucoepidermoid carcinomas and its usefulness as an indicator in tumor progression, aggressiveness, and prognosis., Methods: Thirty-one patients with mucoepidermoid carcinomas who had surgical resection were studied retrospectively. Clinicopathologic features, including histologic types, T stage, nodal status, perineural invasion, overall AJCC stage, and survival data, were obtained from medical records. Immunohistochemical staining with monoclonal antibodies against p27(Kip1) was performed on the formalin-fixed, paraffin-embedded specimens from each patient. The percentage of tumor cells expressing p27(Kip1) (labeling index) was evaluated by counting 1000 cells per slide in at least four different areas and comparing with the patients' clinicopathologic features and survival rates., Results: Significant correlation was found between low p27(Kip1) expression and tumors with high-grade, advanced T stages, positive nodal status, and advanced clinical stages (p =.001 for all) except perineural invasion. Multivariate analysis indicated that p27(Kip1) expression (p =.030) was the most significant, and gender (p =.048) was the next significant predictor of overall survival among the variables. Also patients with low p27(Kip1) expression showed poor prognosis (p =.002)., Conclusions: We suggest that p27(Kip1) is a reliable independent marker of tumor progression, invasiveness, and prognosis in the mucoepidermoid carcinomas.

The oncoproteins Bcl-2 and Bax, the tumor suppressor gene product p53, TUNEL (TdT [terminal deoxynucleotidyl transferase] dUTP nick end-labeling) and the cell-cycle antigen Ki-67 were studied in 71 cases of mucoepidermoid carcinoma originating in the oral minor salivary glands. Grade I tumors had higher expression of Bcl-2 than Grade II and III tumors (chi2 test, 0.01

Context: Among the cytological and morphological properties of mucoepidermoid carcinoma, one of the most important criteria for measuring its biological behavior and aggressiveness is cell proliferation. In this way, immunohistochemical markers of cell proliferation have been found to be useful in tumor classification and have formed part of the prognostic and therapeutic studies of these pathologies., Objective: To analyze 11 cases of mucoepidermoid carcinoma (MEC) using the proliferation activity marker (PCNA) and to determine its relationship to the grade of malignancy of these tumors., Design: Correlation study., Setting: Head and Neck Surgery Service of Heliópolis Hospital, São Paulo, Brazil., Sample: Slides of 11 cases of primary mucoepidermoid carcinomas of salivary glands were prepared according to routine techniques employed in the Oral Pathology Department of the Dentistry Faculty of São Paulo University, Brazil. They were fixed in a 10% formaldehyde solution and stained with hematoxylin and eosin. After this preparation the tumors were classified as low, intermediate and high grade of malignancy, according to the criteria established by Seifert & Sobin and Auclair, Goode & Ellis. The slides were sent for immunohistochemical processing to evaluate the positivity of proliferating cell nuclear antigen using the streptavidin biotin technique., Main Measurement: The correlation between proliferating cell nuclear antigen expression and the histological malignancy grade in mucoepidermoid carcinoma of salivary glands., Results: there were 4 cases (36%) of low grade, 4 cases (36%) of intermediate grade and 3 cases (27%) of high grade of malignancy. After a comparative study between histological features and immunohistochemical analysis, significant differences were observed (P < 0.01) for low, intermediate and high grades: 16.04%, 26.98% and 56.98% of proliferating cell nuclear antigen expression in mucoepidermoid carcinoma, respectively., Conclusion: The proliferating cell nuclear antigen expression increases with the grade of malignancy in mucoepidermoid carcinoma of salivary glands.

Purpose: To report a case of conjunctival mucoepidermoid carcinoma occurring in a long-standing pterygium in a 33-year-old Cambodian man infected with the human immunodeficiency virus (HIV)., Methods: Review of clinical history and histopathologic findings., Results: A pterygium that was present for 8 years suddenly became highly inflamed and underwent rapid growth. After the initial diagnostic conjunctival and corneal biopsy showed mucoepidermoid carcinoma, subsequent additional deep excisions of the adjacent sclera and cornea were necessary to completely excise the tumor. Cytokeratin and mucicarmine stains were used to confirm the pathologic diagnosis of mucoepidermoid carcinoma., Conclusions: Unique features of this case include the extremely young age of the patient (perhaps rendered susceptible by his HIV infection), the tumor masquerading as a pterygium, and the use of a hybrid lamellar and full-thickness corneoscleral resection requiring a complementary graft. Seventeen months after the resection, the patient is free of tumor; this was histopathologically confirmed with multiple random conjunctival biopsies.

Purpose: Mucoepidermoid carcinoma involving the eye or its adnexa generally arises from the conjunctiva. We describe a nodular lesion of the lower eyelid skin with histologic features consistent with low-grade mucoepidermoid carcinoma., Method: Case report., Results: By histology, the tumor demonstrated areas of squamous cell carcinoma and scattered islands of mucin-secreting cells. Histochemistry showed hyaluronidase-resistant mucin and intense immunoreactivity with an antibody against carcinoembryonic antigen suggesting that the tumor originated from acrosyringeal structures., Conclusions: To our knowledge, this is the first report of a mucoepidermoid carcinoma arising from sweat glands in the eyelid skin.

Background: We have previously studied the immunoreactivity of 3 novel smooth muscle-specific proteins, alpha-smooth muscle actin, smooth muscle myosin heavy chains, and calponin, to assess myoepithelial differentiation in pleomorphic adenomas., Objective: To further expand our knowledge of myoepithelial differentiation in other benign and malignant salivary gland tumors., Design: Formalin-fixed paraffin sections of 135 salivary gland tumors with associated normal glands were stained with monoclonal antibodies using the avidin-biotin complex immunoperoxidase method and enzymatic and microwave heat-induced epitope retrieval., Results: In adenoid cystic carcinomas and epithelial-myoepithelial carcinomas, all 3 markers exclusively highlighted the myoepithelial cell components and the epithelial cells were entirely negative. No immunostaining was detected in canalicular adenomas, oncocytomas, Warthin tumors, acinic cell carcinomas, mucoepidermoid carcinomas, squamous cell carcinomas, and polymorphous low-grade adenocarcinomas. Salivary duct carcinomas and adenocarcinomas, not otherwise specified had a distinctive pattern of uniform periductal staining of reactive myofibroblastic cells, and in salivary duct carcinomas some ducts retained a peripheral immunoreactive myoepithelial cell layer., Conclusion: Immunoreactivity for these 3 smooth muscle-specific proteins confirms the known neoplastic myoepithelial component of adenoid cystic carcinomas and epithelial-myoepithelial carcinomas. The consistently positive staining pattern in adenoid cystic carcinomas may be diagnostically useful in discriminating histologically similar but consistently negative polymorphous low-grade adenocarcinomas. Periductal linear staining in adenocarcinoma, not otherwise specified and salivary duct carcinomas is distinctive and appears to represent a tight cuff of myofibroblasts associated with the infiltrating glands.

The NCI-H292 cell, a human pulmonary mucoepidermoid carcinoma cell line, is commonly used for studying bacterial and viral infections of airway epithelial cells. Dysfunction of the cystic fibrosis transmembrane conductance regulator (CFTR) is the main cause of fetal lung infection in cystic fibrosis patients. In this study, we examined CFTR expression in NCI-H292 cells to determine whether NCI-H292 cells possess sufficient, normally functioning CFTR. The results of RT-PCR and Northern blotting analysis indicated that the CFTR gene expression level was much lower in NCI-H292 cells than in T84 cells. However, Western blotting analysis showed that protein expression in NCI-H292 cells was comparable to that in T84 cells. Furthermore, whole-cell and cell-attached patch clamp electrophysiological techniques indicated that the Cl- current induced by intracellular cAMP elevation in NCI-H292 cells was comparable to that in T84 cells. These findings suggest that NCI-H292 cells with a low level of CFTR gene expression possess enough functional CFTR to show a physiological response.

p27(Kip1), a cyclin-dependent kinase (CDK) inhibitor, blocks progression from the G(1) to S phase by binding cyclin E-CDK2 and inhibiting their activities. We studied the expression of p27 in oral tumors by immunohistochemistry to determine whether lack of p27 plays a role in the development and progression of oral cancer. Reduced expression of p27 was detected in 86% of the squamous cell carcinomas and 95% of the mucoepidermoid carcinomas, respectively, while p27 expression was well preserved in the pleomorphic adenomas. The expression of p27 showed an inverse correlation with the expression of cyclin E in the squamous cell carcinomas and mucoepidermoid carcinomas. However, there was no relationship between clinicopathological parameters and p27 expression. These results suggest that the reduction of p27 protein may confer the development of oral squamous cell carcinoma and mucoepidermoid carcinoma partly through the increased expression of cyclin E., (Copyright 2000 S. Karger AG, Basel.)

P53 protein and vascular endothelial growth factor (VEGF) expression, and mean intratumoral microvessel density (IMVD) were studied by immunohistochemistry in 31 salivary gland carcinomas, consisting of 11 adenoid cystic carcinomas (AdCCs), 10 mucoepidermoid carcinomas (MECs), 7 acinic cell carcinomas (AcCCs), and 3 squamous cell carcinomas (SCCs). Cases with p53 protein in more than 20% of tumor cells were detected in one AdCC, four MECs, one AcCC, and two SCCs. Both frequency of p53 and VEGF expression, and mean IMVD, were higher in the MECs and SCCs than in the AdCCs and AcCCs. Similarly, both VEGF expression and mean IMVD were significantly higher (P<0.05) in the eight p53-positive tumors than in the 23 negative tumors. Six cases with survival periods less than 5 years showed significantly higher frequency of p53 and VEGF expression and of mean IMVD than those with longer survival periods. These results indicate that p53 expression might partly correlate with VEGF expression and mean IMVD, and be a factor in the survival of patients with salivary gland carcinomas.

Hydroxymethylglutaryl coenzyme A (HMG-CoA) reductase activities and cholesterol content in the liver of athymic mice either bearing or not an implanted human lung mucoepidormoid carcinoma (HLMC) and in the neoplasic tissue, were analyzed. The properties of the HMG-CoA reductase of HLMC grown in nude mice and those ones found in the liver of these animals, sacrificed either at mid-light or mid-dark, were similar. The hepatic reductase activity was found to be four- to five-fold greater at mid-dark than at mid-light (462 +/- 141 vs. 123 +/- 22 pmol min-1 mg protein-1). Since the Km value was not modified, the mid-dark activity could be due to an increase in the amount of enzyme. In contrast, HLMC reductase activity and cholesterol content showed similar values at mid-light and mid-dark points. HLMC reductase does not appear to have any diurnal variation and the cholesterol synthesis and content seems to be independent of food intake. HLMC-bearing nude mice undergo several alterations in the biosynthesis and homeostasis of cholesterol. Hypocholesterolemia, lower hepatic cholesterol content and higher HMG-CoA reductase activity are characteristic of host mice.

Objective: To investigate the relationship between the differentiation of the mucoepidermoid carcinoma cell line MEC-1 induced by HMBA and the expression of P53 protein., Methods: Effects of HMBA on the growth of MEC-1 cells in vitro were measured with MTT colorimetric assay, and the content of DNA in cells was assayed by using Feulgen's staining. The P53 protein expression of MEC-1 cells was detected with ABC immunohistochemistry with anti-mutant P53 protein antibody, and the distribution of cells in different differentiation phase was determined by flow cytometry., Results: HMBA inhibited the growth of MEC-1 cells in a dose-dependent and time-dependent manner, and HMBA-treated MEC-1 cells were arrested in the G1 phase and had a lower content of DNA and a lower level of P53 protein compared with the control group., Conclusion: The differentiation of MEC-1 cells induced by HMBA may be associated with the regulation of HMBA on the P53 protein expression and the cell differentiation cycle.

Background: Salivary gland tumors have heterogeneous pathological features. Oncogene Bcl-2 product expression inhibits apoptosis and therefore is important for tumor proliferation., Aim: To assess the immunohistochemical gene Bcl-2 protein expression in salivary gland tumors., Material and Methods: Twenty seven salivary gland tumors were selected from the archives of the Pathology Department of Temuco Regional Hospital. There were 20 pleiomorphic adenomas, 4 cystic adenoid carcinomas and three mucoepidermoid carcinomas. Immunohistochemical gene Bcl-2 protein expression was determined in paraffin included pathological slices., Results: All pleiomorphic adenomas expressed the protein, specially in tubulo ductal structures, solid and trabecular areas. All cystic adenoid carcinomas expressed the protein in myoepithelial cells. Two mucoepidermoid carcinomas were positive, only in the epidermoid areas., Conclusions: immunohistochemical gene Bcl-2 protein was expressed in virtually all benign and malignant salivary gland tumors. This observation suggest an important role of this protein in the development of these tumors.

We report on a mucoepidermoid carcinoma (MEC) of the lung in a 6-year-old girl with a t(11;19)(q14-21;p12) as the sole karyotypic abnormality. An apparently identical t(11;19) has been reported previously in a MEC originating from the major and minor salivary glands. Our findings indicate that the t(11;19) is intimately associated with the mucoepidermoid phenotype and may be used as a diagnostic marker for this tumour type.

Histological features and prognosis of patients with mucoepidermoid carcinoma of the parotid gland were analysed. Tumours from 13 patients were classified according to histological grades and immunoreactivity for HER-2/neu. Surgical resection of the tumour was performed for all patients, and the overall five-year survival rate was 69 per cent. The patients whose histological grades were 1 or 2 showed a 100 per cent five-year survival rate, but no patient with grade 3 survived five years. Also, patients who had tumours that overexpressed HER-2/neu had a lower survival rate (25 per cent) than patients with tumours that had weaker immunostaining (89 per cent). We considered tumours classified as grade 3 plus strong HER-2/neu expression to be 'high malignancy', and compared them with 'low malignancy' tumours that were grade 1 or 2 and had weaker HER-2/neu staining. Patients with high malignancy tumours had shorter recurrence-free intervals and shorter overall survival than patients with low malignancy tumours. The overall survival period of the low malignancy cases was much longer than the recurrence-free interval; unlike that in the high malignancy tumour patients. These results suggest that the combination of histological grades and expression of HER-2/neu may be a useful predictor of the prognosis for mucoepidermoid carcinomata.

Aims: Malignant transformation of Warthin's tumour (WT) is a rare event. We present two cases of mucoepidermoid carcinoma (MEC) arising in WT in the parotid gland., Methods and Results: Two cases of MEC arising in WT, which were found in 185 cases of WT of the parotid gland, were investigated by light and electron microscopy, and immunohistochemistry. Both cases had largely similar macroscopic and histological features with some differences. Histologically, the tumours consisted mainly of WT with multilayered hyperplastic arrangements of oncocytic cells and focal squamous and goblet cell metaplasia. In the same tumour mass, however, the features of MEC were observed with invasion to adjacent adipose tissue. A transitional zone between WT and MEC was evident. Both patients were alive and well without evidence of recurrence 30 and 34 months after surgery, respectively. Electron microscopy revealed that cyst lining epithelial cells in WTs had abundant mitochondria whereas some of the MEC cells contained numerous tonofilaments and mucinous granules. Immunohistochemically, oncocytic cells of WTs were strongly positive for mitochondria and SalylTn was extensively stained in MECs. The labelling index for Ki67 was obviously higher in the carcinoma cells than the epithelial cells of WT., Conclusions: Our cases confirmed the possibility of malignant transformation of the epithelial component in WT to MEC.

The expression of cytokeratins (CKs) 7,8,10,13,14,18,19, vimentin and muscle-specific actin (MSA) was investigated in 17 mucoepidermoid carcinomas (MEC) by the streptavidin-biotin technique. The results revealed that CKs 7, 8 and 18 were positive for intermediate, luminal columnar and mucous cells. For epidermoid cells, the expression was heterogeneous and discrete. The reaction with CK19 was similar to that seen for the above CKs, except for the fact that mucous cells were negative. CK 14 was preferentially expressed in the intermediate cells localised in basal, parabasal and epidermoid cells. CK13 was localised in intermediate, epidermoid and luminal columnar cells. In stratified epithelium, CK13 was expressed in intermediate cells and negative in basal cells. These findings were more expressive in cystic areas of the tumours. CK10 was negative for all the cases studied. MSA was positive only in stromal elements, and only two cases of CME were heterogeneously positive for vimentin. The result obtained showed that the immunoprofile of MEC, for the studied antigens, is similar to that exhibited by the excretory duct of normal salivary glands.

Twenty-five cases of mucoepidermoid carcinoma of the salivary glands were studied with respect to clinico-pathologic features, prognostic factors, and c-erbB-2 oncoprotein expression. Fourteen cases were located in parotid glands, 2 in submandibular glands and 9 in minor salivary glands. Fourteen patients were confirmed to have local recurrences, 6 patients manifested systemic metastases, and 10 patients died of the disease. They were histologically graded as I in 5, II in 12 and III in 8 cases respectively, and the histologic grade was significantly correlated with disease-free interval and overall survival of the patients. c-erbB-2 overexpression was observed in 9 cases (36%), with a trend to be associated with the higher grade, but was not evaluated as a significant survival-related factor in this series. Larger size and major gland location of the tumors were correlated with more frequent regional lymph node metastases. The present study showed that c-erbB-2 overexpression was not uncommonly present in mucoepidermoid carcinoma of the salivary glands, especially of higher grade, and the histologic grade was the most important and handy prognostic indicator.

In recent years, a tumor suppressor gene nm23 has been found to be associated with decreased tumor metastatic potential. Allelic deletion, mutation and low expression of this gene has been correlated with tumor metastatic potential in a number of tumors. We examined the expression of nm23 in 40 cases of salivary gland malignant carcinomas by immunohistochemical method. The results showed that nm23 lower expression tumors were associated with a higher rate of metastasis (81.8%) than nm23 higher expression (3.4%, P < 0.005). There is no correlation between nm23 lower expression and tumor size, location and pathologic type (P > 0.05). This result indicates that nm23 gene plays an important role in the metastasis of salivary gland malignant carcinoma.

The expressions and distributions of PCNA and p53 protein were studied with anti-PCNA and anti-p53 protein MoAbs, using immunohistochemical staining method in salivary gland tumour. The relationship between PCNA and p53 protein was also studied. Results indicated: Malignant mixed tumour (MmT) had a higher proliferating index (PI) of PCNA. The PI could be used as one of adjuvant diagnostic criteria; and as an important parameter for grading mucoepidermoid carcinoma (MEC); The positive expression of p53 might be a good tumour marker for MmT; Tumour tissues with positive expression of p53 had been shown higher PI of PCNA, however there was no significance difference in our group; It remained to be studied later.

Immunoreactivity of proliferating cell nuclear antigen (PCNA) was assessed in formalin-fixed, paraffin-embedded sections from human normal parotid gland (N; n = 12), chronic sialadenitis (CS; n = 8), Warthin's tumour (W; n = 10), benign pleomorphic adenoma (BPA; n = 11), mucoepidermoid carcinoma (MEC; n = 14), carcinoma in pleomorphic adenoma (CPA; n = 10) and adenoid cystic carcinoma (ACC; n = 12) of the parotid gland, using the monoclonal antibody PC 10. The morphometric parameters measured comprised PCNA labelling induces (PI = the numerical percentage of PCNA positive nuclei) and volume densities of PCNA positive nuclei(VV, PEP = the relative volume of positive nuclei per unit volume of reference epithelium). All parameters were expressed in relation to total positive, as well as to strongly- and weakly-positive nuclei. In general, the values of PCNA parameters increased progressively in benign lesions in comparison with the N group, and in malignant neoplasms in comparison with non-neoplastic groups and benign lesions. The strongly-positive parameters showed more statistically significant differences than weakly-positive ones, suggesting that weakly-stained nuclei may include some non-cycling cells and, therefore, that weakly-positive parameters may not be reliable proliferation markers. Values for all parameters in CPA were significantly higher than those in BPA, suggesting that these parameters may be used as diagnostic discriminators. Spearman rank correlation analysis showed a highly positive correlation between the morphometric parameters and the severity of the lesions. Furthermore, the mean values of PISP were significantly higher in patients who died of the malignant tumours than in those patients who survived. Our results indicate that PCNA indices might be useful markers for discriminating between benign (BPA) and malignant tumours of the parotid gland and that the parameter PISP may have prognostic applications.

Clinical, histological and immunohistochemical data on 71 parotid gland tumors were analyzed. Benign neoplasms accounted for 71.8% of the case material and malignant tumors 22.6%. Chronic parotitis occurred in 5.6% of the total case number. Pleomorphic adenomas and mucoepidermoid carcinomas were the most frequently occurring benign and malignant neoplasms. Pleomorphic adenomas stained positive for S-100 protein, tenascin, smooth muscle actin, synaptophysin and chromogranin A. This immunohistochemical, histological and clinical analysis was believed to be of potential assistance in the diagnosis, treatment and prognosis of parotid gland tumors.

To explore the expression of proliferating cellnuclear antigen (PCNA) and tumor suppressor gene P53 product in mucoepidermoid carcinoma of the salivary glands, we studied 41 cases by immunohistochemical method. All of the cases were PCNA positive. The positive index, distribution pattern and cellular staining intensity for PCNA expression were correlated with carcinoma grade. P53 protein expression was found in 17 (41.5%) of the 41 cases; among them the expressions were weak in 9 cases. These results indicate that positive index, distribution pattern and cellular staining intensity of PCNA expression may be served as an indicator for evaluating the differentiating degree of the tumor.

The effect of lovastatin, a hypocholesterolemic drug, on tumor growth and desaturase activity was studied in a human lung mucoepidermoid carcinoma (HLMC) grown in nude mice. After administration of a diet supplemented with 25 mg% (w/w) lovastatin for 30 days the growth of HLMC was not inhibited. Liver and tumor phospholipid/cholesterol ratio was increased in lovastatin group but serum cholesterol was unaffected. Treatment with lovastatin increased delta 5 and delta 9 desaturation in tumor microsomes, whereas delta 6 desaturation did not change in tumors of treated mice. The changes were not reflected in the fatty acid composition of total tumor lipids.

Fibroblast growth factor-1 (FGF-1) and FGF-2 are broad spectrum mitogens. The expression of FGF-1, FGF-2, and their receptor, FGF receptor-1 (FGFR-1), was examined in malignant salivary gland tumours and normal salivary glands, using immunohistochemical methods. In seven cases of adenoid cystic carcinoma (ACC), both duct-like cells and modified myoepithelial cells were apparently immunopositive for FGF-1, FGF-2, and FGFR-1. In five cases of mucoepidermoid carcinoma (MC), all three types of tumour cells including epidermoid cells, and intermediate cells expressed immunoreactive FGF-1, FGF-2, and FGFR-1. In these malignant salivary gland tumours, increased expression of FGFR-1 correlated with the intensity of both FGF-1 and FGF-2 immunoreactivity. In contrast to malignant salivary gland tumours, eight cases of normal salivary gland showed negative immunostaining for FGF-1, FGF-2, and FGFR-1 while four cases were weakly immunoreactive for FGF and its receptor. These results demonstrate that malignant salivary gland tumours overexpress FGF-1, FGF-2, and FGFR-1 compared with normal salivary glands and suggest that these growth factors may play an important role in facilitating neoplastic progression in human salivary glands.

The aim of the present study was the evaluation of CEA-radio-immunoassay and CEA-immunohistochemistry in the management of pleomorphic adenoma and mucoepidermoid carcinoma of salivary glands. 23 pleomorphic adenomas, 9 mucoepidermoid carcinomas, and 7 normal salivary glands were examined. CEA-concentration in serum and saliva were assayed before and after surgery. Polyclonal CEA antibody was used for immunohistochemical CEA detection in the tumor tissue and in the normal salivary glands. The mean CEA concentrations were found to be 14.94 ng/ml in the serum and 216.67 ng/ml in the saliva of patients with mucoepidermoid carcinoma. These values were considerably higher compared to healthy controls (188.64 ng/ml in saliva) and in patients with pleomorphic adenoma - 7.65 ng/ml in serum and 189.35 ng/ml in saliva (P < 0.001). A correlation was found between high CEA concentration in the saliva and the intensity of CEA expression in the tumour tissue. An increased synthesis and secretion of CEA was determined by the prevalence of tubular structures, a high proliferative activity in pleomorphic adenoma, and its malignant transformation.

Mucoepidermoid carcinoma is the most common malignant tumor of salivary glands. In this report, we used hexamethylene bisacetamide (HMBA) as a inducer to induce human mucoepidermoid carcinoma cell line MEC-1 cells to differentiate. The growth kinetics, morphological changes and DNA contents of the cells were investigated. The results showed that HMBA-treated MEC-1 cells tend to become mature cells, implying that HMBA can induce differentiation of MEC-1 cells in vitro.

Tenascin, a large molecular weight extracellular glycoprotein expressed at the epithelial-mesenchymal interface during morphogenesis in embryo, wound healing and in the stroma of various benign and malignant tumours was evaluated in a series of primary epithelial tumours of salivary glands using a monoclonal antibody. Normal salivary glands (n = 5) had linear delicate band-like immunoreactive tenascin in relatively large excretory or intralobular ducts. Pleomorphic adenomas (n = 40) had heterogeneity of expression in modified myoepithelial cell-associated myxoid, hyaline and chondroid areas. Warthin's tumours (n = 10) had a linear immunoreactivity profile of tenascin just adjacent to the basal cells of the epithelial tumour component. A heterogeneity of expression with intense to low or negative stromal immunoreactivity was observed in adenoid cystic carcinomas (n = 8), mucoepidermoid carcinomas (n = 8), epithelial-myoepithelial carcinomas (n = 4), polymorphous low-grade carcinomas (n = 3), papillary cystadenocarcinomas (n = 15) and undifferentiated carcinomas (n = 3). In addition, small cystic spaces or lumens of epithelial-lined tubulo-ductal structures in numerous salivary tumours had positive immunoreactivity for tenascin, suggesting its production by the epithelial tumour component. An enhanced expression of tenascin in salivary tumours suggests a role of this protein in the stromal remodelling and tumour growth.

The level of c-erbB-2 cellular mRNA in 18 salivary gland tumours and in 7 normal salivary glands was determined by in situ hybridization using [35S] labelled RNA probes. Computer assisted quantitation of the autoradiographic signal indicated a significantly higher c-erbB-2 expression in the tumour group (22.64 grains per cell +/- 3.79; 95% CI) as compared to the non-neoplastic salivary gland tissue (4.11 +/- 0.90; 95% CI). The c-erbB-2 expression as measured by grain counts per cell for the pleomorphic adenomas (16.29 +/- 1.87; 95% CI), mucoepidermoid carcinomas (31.52 +/- 0.08; 95% CI) and the acinic cell carcinomas (44.24 +/- 17.11; 95% CI) were significantly greater than the expression for the normal group. The acinic cell carcinomas exhibited the greatest level of expression. As observed at the individual cell level, the autoradiographic signal was distributed uniformly in the neoplastic tissues, regardless of the cell type. This study confirms the hypothesis that the c-erbB-2 oncogene is overexpressed at the mRNA level in salivary gland tumours.

Among 1058 patients with cancer of the esophagus, 20 patients with mucoepidermoid or adenosquamous cell carcinoma of the esophagus and cardia, together defined as squamous cell carcinoma with a mucin-secreting component, were seen over a 10-year period. Their records were reviewed and appropriate comparisons were also made with the more common squamous cell carcinomas and adenocarcinomas. Squamous cell carcinoma with mucin-secreting component comprised 1.9% of all tumors encountered. Clinical features including age, male predominance, symptoms at presentation, length of tumor, and appearance of tumor did not differ from those of squamous cell and adenocarcinoma. The location of these tumors, however, followed that of squamous cell carcinomas, with 55% in the middle third and 25% in the lower third. Adenocarcinomas were found predominantly at the cardia (83%). Operability and resectability rates were higher than those of squamous cell and adenocarcinomas. Primary treatment consisted of resection in 19 of the 20 patients (95%); 18 of them had a one-stage resection and 1 patient had a two-stage resection. Postresection staging showed that 5% had stage I disease, 16% had stage II, and 79% had stage III disease. None of the patients who underwent resection died within 30 days of the operation. The mortality after 30 days was 10.5%. The 1 patient in whom intubation was the primary treatment had distant metastases at the time of presentation (stage IV). The overall median survival was 9.2 months. The median survival for patients who had their tumors resected was 9.5 months. The survival improved to 33 months for curative resection but was only 8.7 months for palliative resection. The 1-, 2-, and 5-year survivals were 46%, 39%, and 0%, respectively. This prognosis was not significantly different from that of patients with squamous cell carcinoma or adenocarcinoma.

Aims: To determine the direction of differentiation of the mucin secreting components in a rare group of oesophageal tumours--oesophageal squamous cell carcinomas with prominent mucin secreting components (mucoepidermoid carcinomas and adenosquamous carcinomas)., Methods: In a review of 617 cases of primary carcinoma of the oesophagus, 16 cases of squamous cell carcinoma with prominent mucin secreting components were studied using a battery of histochemical techniques., Results: The mucin produced by these tumours was mixed and included a variable content of enzyme labile sialomucin (positive for mucicarmine, periodic acid Schiff, and alcian blue, and sensitive to sialidase digestion and negative for high iron diamine-alcian blue). Retrospective analysis of endoscopic biopsy specimens taken from these tumours showed that mucin was present in five (42%) cases., Conclusions: The glandular component of this group of tumours histochemically differentiated in the direction of oesophageal glands: examination of the mucin secreting component in squamous cell carcinoma in resected specimens is therefore required for recording the true incidence of this type of tumour.