Carcinoma Ex Pleomorphic Adenoma Research Articles

Cytomorphologic Spectrum of Carcinoma ex Pleomorphic Adenoma

To delineate the cytomorphologic features of carcinoma ex pleomorphic adenoma (CPA) and identify the diagnostic pitfalls. Smears of 14 cases suspected as CPA on fine needle aspiration over a period of 15 years were reviewed. Cytohistologic correlation was done in 10 cases. All cases had a salivary gland mass of 1-16 years' duration, with a rapid increase in size in 10 cases. Epithelial cells predominated over stroma in 11 of 14 cases. Group I showed unequivocal malignant cells admixed with benign epithelial and stromal components of pleomorphic adenoma (PA), which were considered diagnostic of CPA on review. The cytologic differential diagnosis in these cases included mucoepidermoid carcinoma, carcinosarcoma and metastatic adenocarcinoma. Group II comprised 7 cases suspected to be cellular PA with atypia or CPA. These showed mild to moderate degrees of pleomorphism, absence of unequivocal malignant cells, and a variable proportion of benign epithelial and stromal components. Four of them were histologically confirmed as CPA. Sampling error is an important cause of diagnostic pitfalls. Correlation with clinical data is essential in diagnosis of CPA on cytology. In a proper clinical setting, extensive fine needle aspiration sampling should be done initially. Any degree of nuclear atypia in PA should be documented, alerting the clinician and histopathologist to the possibility of CPA.

Immunohistochemical expression of retinoblastoma pathway proteins in normal salivary glands and in salivary gland tumours

The expression of G1-phase cell-cycle regulators is commonly deregulated in human malignancies. In the present study, we investigate components of the retinoblastoma (RB) pathway in normal salivary glands (NSG) and in salivary gland tumours (SGT). Samples of NSG, pleomorphic adenoma (PA), adenoid cystic carcinoma (ACC), mucoepidermoid carcinoma (MEC), epithelial-myoepithelial carcinoma (EMC), malignant myoepithelioma (MEM), carcinoma ex pleomorphic adenoma (CEPA), and polymorphous, low-grade adenocarcinoma (PLGA) were examined immunohistochemically using antibodies to cyclin D1, cyclin-dependent kinase 4 (CDK-4), retinoblastoma protein (pRb), CDK inhibitor p16 and transcription factor E2F-1. In normal salivary glands, cyclin D1 and cdk-4 were not expressed in any case while p16 was positively expressed. pRb was abundant and E2F-1 moderately expressed. In tumors, cdk-4 was overexpressed in half of the cases. Most tumour cases showed decreased pRb immunoexpression compared to normal salivary glands. In contrast, expression of p16 and E2F-1 increased. pRb expression was absent in three cases of PA, two of EMC and one of CEPA. One case of MEM and one of PLGA showed no E2F-1 expression. Statistical analyses revealed positive correlations between cyclin D1 and cdk-4, cyclin D1 and E2F-1, cdk-4 and E2F-1, and p16 and E2F-1. The benign and malignant tumours expressed retinoblastoma pathway proteins differently form the normal salivary gland. Our findings suggest that, pRb pathway deregulation in salivary gland neoplasms is unrelated to their biological behaviour.

Neural adhesion molecule (N-CAM) in pleomorphic adenoma and carcinoma ex-pleomorphic adenoma.

The neural cell adhesion molecule (N-CAM) has been implicated in the behaviour of the adenoid cystic carcinoma. In vitro, it was demonstrated that N-CAM inhibits cell invasion. The aim of this study was to search for N-CAM in the most common salivary gland tumour that has a malignant counterpart. We investigated the presence of N-CAM in pleomorphic adenoma and its malignant counterpart, the carcinoma ex-pleomorphic adenoma, using the immunohistochemistry technique. Neural cell adhesion molecule was expressed in all cases of pleomorphic adenoma, strongly labelling the luminal cells of the double-layered ductform structures. This expression was weaker in neoplastic myoepithelial cells and progressively diminished at a distance from the luminal cells. In carcinoma, ex-pleomorphic adenoma N-CAM was either totally absent or faintly present at the apical pole of the few luminal cells. As a result of the peculiar distribution of N-CAM in pleomorphic adenoma, we speculated that N-CAM behaves as a tumour-suppressor molecule, which is expressed in the benign neoplasm and which is down-regulated after malignancy, when the tumour assumes an invasive behaviour.

Mucoepidermoid carcinoma expleomorphic adenoma of the submandibular gland

We described a rare case of carcinoma expleomorphic adenoma in which mucoepidermoid carcinoma arise from a previous incompletely excised pleomorphic adenoma of the submandibular gland. The tumor was surgically resected along with a modified radical neck dissection and postoperative radiotherapy. The patient remained disease free 3 years after the last operation. The pathology showed concurrent presence of Warthin’s tumor in the specimen. The concurrent presence of mucoepidermoid carcinoma, pleomorphic adenoma, and synchronous Warthin’s tumor make this case unique, and such a combination associated with the submandibular gland has not been documented in the literature before.

Acinic cell adenocarcinoma - a case report

Acinic cell adenocarcinoma is a malignant salivary gland tumour with cells that show serous acinar differentiation. Clinically if the site is the parotid gland. it may resemble a pleomorphic adenoma. Herewith we present a case of acinic cell adenocarcinoma in a 60 ­year old male who reported with a lobulated swelling in the parotid region, which was clinically diagnosed as pleomorphic adenoma or carcinoma ex-pleomorphic adenoma and histologically diagnosed as acinic cell adenocarcinoma.

Increase in immune cell infiltration with progression of oral epithelium from hyperkeratosis to dysplasia and carcinoma.

In the present study, epithelium derived lesions of various pathological manifestations were examined histologically and immunohistochemically for mononuclear cell infiltration. The infiltrate under the transformed epithelium of oral lesions, was examined for differences in the composition of immune mononuclear cells as the epithelium moves from hyperkeratosis through various degrees of dysplasia to squamous cell carcinoma. The study was performed on 53 human tongue tissues diagnosed as hyperkeratosis (11 cases), mild dysplasia (nine cases), moderate and severe dysplasia (14 cases) and squamous cell carcinoma (19 cases). A similar analysis was performed on 30 parotid gland tissues diagnosed as pleomorphic adenoma (14 cases) and carcinoma ex-pleomorphic adenoma (16 cases). Immunohistochemical analysis of various surface markers of the tumour infiltrating immune cells was performed and correlated with the transformation level as defined by morphology and the expression of p53 in the epithelium. The results revealed that, in the tongue lesions, the changes in the epithelium from normal appearance to transformed were accompanied by a corresponding increase in the infiltration of CD4, CD8, CD14, CD19+20, and HLA/DR positive cells. The most significant change was an increase in B lymphocytes in tongue lesions, that was in accordance with the transformation level (P<0.001). In the salivary gland, a significant number of cases did not show an infiltrate. In cases where an infiltrate was present, a similar pattern was observed and the more malignant tissues exhibited a higher degree of immune cell infiltration.British Journal of Cancer (2002) 86, 1444–1448. DOI: 10.1038/sj/bjc/6600282 www.bjcancer.com© 2002 Cancer Research UK

Role of fine needle aspiration cytology in diagnosis of pleomorphic adenomas.

This retrospective study was carried out to review the cases diagnosed as pleomorphic adenoma in major or minor salivary glands and determine the difficulties encountered on typing this tumour on fine needle aspiration cytology (FNAC). Over a 19-year period (1982-2000) 488 pleomorphic adenomas were diagnosed on FNAC from different sites (parotid - 372 cases, submandibular - 95 cases; oral cavity - 21 cases). Histology was available in 232 cases. Twenty-nine cases where a histological diagnosis of pleomorphic adenoma was made but the cytological diagnosis was variable were also reviewed. In 216 of the 232 cases a good cytohistological correlation was available. On review only 4 of the 16 cases initially diagnosed as pleomorphic adenoma on FNAC where the histology revealed a different tumour were categorized as pleomorphic adenoma, while 3 each were classified as adenoid cystic carcinoma and benign tumour ?type, and 2 each were diagnosed to be muco-epidermoid carcinoma, monomorphic adenoma and acinic cell carcinoma. On review of the FNAC smears from 29 cases where a histological diagnosis of pleomorphic adenoma was available while the cytological diagnosis was variable, only 11 (38%) were categorized as pleomorphic adenoma. In the majority of the remaining cases the cytological diagnosis did not alter markedly, 7 of 10 cases where the tumour could not be typed on cytology initially could not be typed even on review. In conclusion, FNAC is an ideal, fairly accurate preoperative procedure for the diagnosis of pleomorphic adenomas. Certain diagnostic problems occur in differentiating pleomorphic adenomas from adenoid cystic carcinoma, monomorphic adenoma and mucoepidermoid carcinoma. Carcinoma ex-pleomorphic adenoma is difficult to identify on FNAC and in our series all 4 such cases on histology were considered benign on cytology.

Translocation, Deletion/Amplification, and Expression of HMGIC and MDM2 in a Carcinoma ex Pleomorphic Adenoma

Carcinoma ex pleomorphic adenoma (CexPA) is a carcinoma developing within a pre-existing benign pleomorphic adenoma (PA). Here we describe the identification and characterization of a series of genetic events leading to translocation, deletion/amplification, and overexpression of the HMGIC and MDM2 genes in a CexPA at an early stage of development. The tumor had a pseudodiploid stemline karyotype with a del(5)(q22-23q32-33) and a t(10;12)(p15;q14-15). In addition, there were several sidelines with double minute chromosomes (dmin) or homogeneously staining regions (hsr). Fluorescence in situ hybridization (FISH) mapping revealed that the 12q14-15 breakpoint was located centromeric to HMGIC and that the entire gene was juxtaposed to the der(10) chromosome. Detailed analysis of cells with dmin and hsr revealed that HMGIC and MDM2 were deleted from the der(10) and that the dmin and hsr were strongly positive for both genes. Southern blot analysis confirmed that both HMGIC and MDM2 were amplified and that no gross rearrangements of the genes had occurred. Immunostaining revealed that the HMGIC protein was highly overexpressed particularly in the large polymorphic cells within the carcinomatous part of the tumor. These findings suggest that amplification and overexpression of HMGIC and possibly MDM2 might be important genetic events that may contribute to malignant transformation of benign PA.

Carcinoma ex pleomorphic adenoma: Pathologic analysis of 73 cases

Pathologic factors of predictive value for carcinoma ex pleomorphic adenoma (CXPA), an aggressive salivary gland malignancy, are poorly defined. Because residual mixed tumor may be relatively inconspicuous and various carcinoma subtypes are encountered, misdiagnosis is common. To describe the pathologic features and identify potential prognostic factors, we retrospectively examined 73 cases of CXPA of the major salivary glands treated at Mayo Clinic. Paraffin section immunostaining for keratins (AE1/AE3, CK7, CK20), epithelial membrane antigen, carcinoembryonic antigen, vimentin, actin, S-100 protein, glial fibrillary acidic protein, and p53 and c-erbB-2 oncoproteins was performed in 69 cases. DNA content and proliferation indices were determined by digital image analysis of Feulgen- and MIB-I-stained sections, retrospectively. Survival was calculated by the Kaplan-Meier method, and prognostic variables were analyzed with the log-rank test. The carcinoma component was predominant in 82% of tumors. Adenocarcinoma not otherwise specified (31 cases) and salivary duct carcinoma (24 cases) were the most frequent histologic subtypes. Sixty-two tumors were high grade (Broders 3 or 4). Residual mixed tumor was extensively hyalinized in 54 cases. Pathologic features significantly associated with overall survival included pathologic stage (P =.009), tumor size (P =.012), grade (P =.005), proportion of carcinoma (P =.004), extent of invasion (P =.002), and proliferation index of carcinoma (P =.03). Of 4 patients with intracapsular (noninvasive) carcinoma, none had an adverse outcome. The immunohistochemical profile of CXPA included positive staining reactions in the malignant component for AE1/AE3 in 97% of cases, CK7 in 94%, epithelial membrane antigen in 86%, carcinoembryonic antigen in 75%, vimentin in 52%, and S-100 protein in 29%. Expression of p53 and c-erbB-2 oncoproteins was detected in 41% and 30% of the carcinomas, respectively, but neither was associated with decreased survival. High-grade salivary adenocarcinoma that is difficult to classify should raise the suspicion of possible CXPA. Intracapsular carcinoma has a benign clinical course. Significant prognostic factors in CXPA include tumor stage, grade, proportion of carcinoma, extent of invasion, and proliferation index. HUM PATHOL 32:596-604. Copyright © 2001 by W.B. Saunders Company

Characterization of chromosome aberrations in salivary gland tumors by FISH, including multicolor COBRA-FISH

Fluorescence in situ hybridization (FISH), including COBRA-FISH, was used to characterize 11 salivary gland tumors that had been investigated by banding analysis. Five cases were pleomorphic adenoma (PA), three were adenoid cystic carcinoma, and one case each was mucoepidermoid carcinoma, carcinoma ex-pleomorphic adenoma (CaPA), and adenocarcinoma. All 11 cases were selected on the basis that they had shown rearrangement of 6q or 9p or had unresolved aberrations after karyotyping. The COBRA-FISH and FISH analyses led to a revised karyotype in all informative cases and made it possible to clarify almost all chromosomal rearrangements occurring in the tumors. Of particular note were the confirmation of the existence of 6q deletions, a common change in salivary gland carcinomas, and the demonstration that a seemingly balanced t(6;9) resulted in del(6q). Other rearrangements that were revealed by FISH included amplification of 12q sequences (MDM2 and CDK4) in one PA. We also investigated the status of the PLAG1 gene in four cases (one PA, one CaPA, one adenoid cystic carcinoma, and one mucoepidermoid carcinoma) with 8q12 rearrangements. Only in the former two cases were the FISH results compatible with intragenic rearrangements. Overall, the results of the study show that, even with good banding quality and in karyotypes of modest complexity, much new information will be gained by supplementing the banding analysis with a multicolor FISH approach, such as COBRA-FISH.

Malignant transformation of a gigantic pleomorphic adenoma of the submandibular gland: A case report

Carcinoma ex pleomorphic adenoma (CPA) is a tumor showing definitive evidence of malignancy in part of a previously benign pleomorphic adenoma (PA). 1 Seifert G Sobin LH Histological Typing of Salivary Gland Tumors. ed 2. World Health Organization, Geneva, Switzerland,1991 Crossref Google Scholar The CPA has been reported to represent 1.4% to 17.5% of all salivary gland tumors 2 Stuteville OH Corley RD Surgical management of tumors of intraoral minor salivary glands. Cancer. 1967; 20: 1578 Crossref PubMed Scopus (50) Google Scholar and from 1.7% to 4.2% of submandibular tumors. 3 Eneroth CM Salivary gland tumors in the parotid gland, and the palate region. Cancer. 1971; 27: 1415 Crossref PubMed Scopus (276) Google Scholar , 4 Thackray AC Lucas RB Tumors of the major salivary glands, in Atlas of Tumor Pathology. Armed Forces Institute of Pathology, Washington, DC1974 Google Scholar We report a case of CPA of the submandibular gland in which malignant transformation was suspected because a size of the lesion and its recent rapid growth.

Differential expression of galectin-1 and galectin-3 in benign and malignant salivary gland neoplasms.

Galectins are a family of non-integrin beta-galactosidase-binding lectins. Altered expression of galectins has been associated with neoplastic transformation and progression in several human tumors. In this study, we examined the distribution patterns of galectin-1 and galectin-3 in normal (n=45), benign (n=16), and malignant (n=49) salivary gland specimens using immunohistochemistry to determine their diagnostic and/or biological implications in salivary gland tumorigenesis. In normal salivary glands, galectin-3 expression was limited to ductal cells, and galectin-1 was usually faintly detected in ductal cells and strongly positive in myoepithelial cells. In benign tumors, galectin-3 maintained the ductal localization, but galectin-1 showed variable expression in ductal and myoepithelial cells. In malignant tumors, most of the polymorphous low-grade adenocarcinomas and carcinoma ex-pleomorphic adenomas expressed both galectins, whereas adenoid cystic and acinic cell carcinomas showed dramatically reduced galectin-3 expression and heterogeneous galactin-1 staining. Our data demonstrated altered localization and expression of galectin-3, and to lesser extent, galectin-1 in salivary gland carcinomas. These findings may assist in the differential diagnosis of some salivary gland malignancies, especially when using small and limited fine-needle aspiration materials.

Molecular genetic alterations in carcinoma ex-pleomorphic adenoma: A putative progression model?

To determine the genetic changes associated with the development of carcinoma ex-pleomorphic adenoma (Ca Ex-PA), we analyzed 15 microsatellite loci at chromosome arms 8q, 12q, and 17p on DNA from 26 neoplasms (including 8 microdissected benign and malignant components), and 13 pleomorphic adenomas for comparison. Pleomorphic adenomas and the adenoma component of Ca Ex-PAs showed a higher incidence of loss of heterozygosity (LOH) at chromosome arms 8q (52%) and 12q (28%) than at 17p (14%) loci. In the carcinoma component, the combined LOH at chromosome arm 8q, 12q, and 17p regions was 69%, 50%, and 69%, respectively; within these chromosomal regions, 8q11.23-q12 (42%), 12q23-qter (39%), 17p13 (41%), and 17p11 (45%) loci manifested the highest incidence of LOH. Eight carcinomas (30.7%) showed loss at all three chromosomal arms tested. Of the eight microdissected Ca Ex-PAs analyzed, four adenoma and corresponding carcinoma components (50%) had the same LOH at 12q loci and additional LOH at 17p loci only in carcinomas. Chromosome arm 17p alterations correlated significantly with high disease stage and an increased proliferative rate in these tumors. Our results indicate that alterations at regions on chromosome arms 8q and/or 12q may constitute early events associated with pleomorphic adenomas; that LOH at 12q loci may identify a subset of adenoma with potential progression to carcinoma; that acquisition of additional alterations at chromosome arm 17p loci might represent an event preceding malignant transformation and progression; and that 8q, 12q, and 17p regions may harbor tumor suppressor genes involved in the genesis of PA and Ca Ex-PA. Genes Chromosomes Cancer 27:162-168, 2000.

Molecular genetic alterations in carcinoma ex‐pleomorphic adenoma: A putative progression model?

To determine the genetic changes associated with the development of carcinoma ex-pleomorphic adenoma (Ca Ex-PA), we analyzed 15 microsatellite loci at chromosome arms 8q, 12q, and 17p on DNA from 26 neoplasms (including 8 microdissected benign and malignant components), and 13 pleomorphic adenomas for comparison. Pleomorphic adenomas and the adenoma component of Ca Ex-PAs showed a higher incidence of loss of heterozygosity (LOH) at chromosome arms 8q (52%) and 12q (28%) than at 17p (14%) loci. In the carcinoma component, the combined LOH at chromosome arm 8q, 12q, and 17p regions was 69%, 50%, and 69%, respectively; within these chromosomal regions, 8q11.23–q12 (42%), 12q23–qter (39%), 17p13 (41%), and 17p11 (45%) loci manifested the highest incidence of LOH. Eight carcinomas (30.7%) showed loss at all three chromosomal arms tested. Of the eight microdissected Ca Ex-PAs analyzed, four adenoma and corresponding carcinoma components (50%) had the same LOH at 12q loci and additional LOH at 17p loci only in carcinomas. Chromosome arm 17p alterations correlated significantly with high disease stage and an increased proliferative rate in these tumors. Our results indicate that alterations at regions on chromosome arms 8q and/or 12q may constitute early events associated with pleomorphic adenomas; that LOH at 12q loci may identify a subset of adenoma with potential progression to carcinoma; that acquisition of additional alterations at chromosome arm 17p loci might represent an event preceding malignant transformation and progression; and that 8q, 12q, and 17p regions may harbor tumor suppressor genes involved in the genesis of PA and Ca Ex-PA. Genes Chromosomes Cancer 27:162–168, 2000. © 2000 Wiley-Liss, Inc.

Laminin and collagen IV in pleomorphic adenoma and carcinoma ex-pleomorphic adenoma: An immunohistochemical study

Laminin and collagen have been studied in several tumor types and their immunomorphological expression correlated with tumor morphogenesis, local invasiveness, and metastatic behavior. In a series of 53 cases of pleomorphic adenomas (PA) and 16 cases of carcinomas ex-pleomorphic adenoma (Ca ex-PA), we investigated by immunohistochemistry the distribution pattern of laminin (lam) and collagen IV (col IV) at the basement membrane (BM) and the interstitial compartments, and their potential relationship with the metastatic behavior of Ca ex-PA. At the BM compartment, lam and col IV were expressed in 37 and 41 of all cases, respectively. In PA, there were lam and col IV around cell aggregates in 47.2% and 56.6% of the cases, respectively, and around isolated cells in 30.2% and 26.4%, respectively. In Ca ex-PA cases, both antigens were expressed in 56.3% and in 18.8% of the cases around cell aggregates and isolated cells, respectively. At the interstitial compartment, the fibro-hyaline matrix contained few lam in PA (19.2%) in contrast to Ca ex-PA (75%), including the benign areas of the neoplasms (90%), being the difference statistically significant ( P < .001). In the Ca ex-PA group, a statistically significant difference was found on col IV deposits around tumor cell aggregates between metastasizing and nonmetastasizing neoplasms ( P < .001). These findings support that laminin and collagen IV are involved in the process of malignant transformation of pleomorphic adenomas and their biological progression.

Concurrent Cytogenetic, Interphase Fluorescence In Situ Hybridization and DNA Flow Cytometric Analyses of a Carcinoma Ex-Pleomorphic Adenoma of Parotid Gland

We report the cytogenetic, fluorescence in situ hybridization (FISH), and DNA ploidy analyses of a high grade carcinoma ex-pleomorphic adenoma of the submandibular gland. Our overall combined analyses showed a marked DNA aneuploidy and numerical abnormalities involving all chromosomes. Cytogenetic analysis revealed a near tetraploid modal chromosomal number with tetraploid loss of chromosomes Y, 1, 6, 9, 11, 14, 15, 17, and 19–21 and hypertetraploid gain of chromosomes 7, 8, and 22. The structural abnormalities included der(1;14)(q10;q10),del(6)(q15q34),+del(6)(q15q34),+der(8)t(1;8)(q12;q12.2),der(9;19)(q10;q10),add(14)(p11.2),i(20)(q10),der(21)t(8;21)(q11.2;q22.3),+der(21)t(8;21)(q11.2;q22.3). Interphase FISH of the primary and short-term cultured cells using directly labeled peri-centromeric probes for chromosomes 6–12, 17, 18, and Y resulted in alterations corresponding to the cytogenetic findings. DNA ploidy analysis of both the primary and cultured tumor cells showed a hyperdiploid stemline with DNA indices of 2.6. The results indicate that: (1) marked numerical, structural chromosomal, and DNA content abnormalities are present in this tumor; and (2) alteration at 8q and 6q regions, together with previous results, suggest an association between these events and the development and/or progression of this tumor.

Genotypic alterations in benign and malignant salivary gland tumors: histogenetic and clinical implications.

Loss of heterozygosity (LOH) and microsatellite instability (MI) were examined at 24 microsatellite loci in 46 primary benign and malignant salivary gland tumors. Among the 27 benign tumors, 11 (40.7%), manifested microsatellite alterations in at least one locus; of these, five (18.5%) showed LOH and four (14.8%) had microsatellite instability at two or more loci. Four of 11 pleomorphic adenomas (36.4%) had allele loss on the long arm of chromosome 8. Among the 19 malignant neoplasms examined, 10 (52.6%) and one (5.2%) had allele losses and MI, respectively, at multiple loci; three tumors showed MI at only one locus. Frequent LOH was detected at D8S166 (8q11-12), D17S799, and D17S122 (17p-17p11-2) loci, with an incidence of 40%, 37.5%, and 43%, respectively. In general, malignant neoplasms with LOH exhibited aggressive tumor characteristics. Statistically significant correlation's were found between LOH and pathologic classification (chi 2, p = 0.05), higher grade (p = 0.02), DNA aneuploidy (p = 0.005), and a proliferative index of > 6% (p = 0.005) of the malignant tumors. Carcinomas with 17p loci alterations, including two carcinomas expleomorphic adenoma with concurrent 8q LOH, showed more aggressive features. The results suggested that (a) loci on chromosome 8q may harbor a tumor suppressor gene or genes associated with the development or progression of some salivary neoplasms; (b) alterations on the short arm of chromosome 17 may represent an event related to tumor progression; and (c) tumors with LOH at multiple loci have aggressive biologic characteristics.

Malignant salivary gland neoplasms: a cytogenetic study of 19 cases.

A group of 19 malignant salivary gland neoplasms of various histological types (mucoepidermoid carcinoma, acinic cell carcinoma, adenoid cystic carcinoma, epithelial-myoepithelial carcinoma, myoepithelial carcinoma, basal cell adenocarcinoma, carcinoma ex-pleomorphic adenoma, ductal carcinoma, adenocarcinoma not otherwise specified and undifferentiated carcinoma) were cytogenetically investigated. Previous karyotypic information revealed deletion of the long arm of chromosome 6, loss of chromosome Y and the gain of chromosome 8 as the most recurrent deviations found in these neoplasms. Clonal chromosome aberrations were detected in 11 cases of this series. In 7 of them there were only numerical deviations (gain of chromosomes 2, 7, 8, 10 and X and loss of chromosomes 18, 21 and Y) without concomitant structural anomalies. Structural rearrangements such as t(2;7), t(6;16), t(6;9) and t(1;1) translocations were found in two mucoepidermoid carcinomas, one adenoid cystic carcinoma and one ductal carcinoma, respectively. The wide spectrum of changes found in this group of neoplasms may reflect the diversity in their histogenesis and differentiation phenotypes.

Immunohistochemical study of c-erbB-2 expression in carcinoma ex-pleomorphic adenoma.

A series of 19 cases of carcinoma ex-pleomorphic adenoma was studied for the immuno-expression of c-erbB-2 oncoprotein. Twelve tumours showed a malignant component with only one histological type; in the remaining seven there was co-existence of areas of various carcinoma types, adenocarcinoma NOS being the most frequent. Membranous c-erbB-2 reactivity was found in 21.1% of the cases, all corresponding to high-grade adenocarcinomatous areas. The low-grade carcinoma types that formed the malignant mixed tumours components were negative. Benign pleomorphic adenoma areas, either adjacent or intermingled with carcinomatous areas, were also consistently negative, proving that c-erbB-2 accumulation is associated with the acquisition of the malignant phenotype. The finding of a preferential association between c-erbB-2 overexpression and high-grade malignant mixed tumour may indicate prognostic implications for the oncogene protein and may also be indicative of its specific relationship with the putative pathway of malignant transformation in pleomorphic adenomas.

11 P - Frequent Loss of Heterozygosity at 6q in Malignant Salivary Gland Tumors

Terminal deletions of the long arm of chromosome 6 (6q) and translocations involving the same region are the only cytogenetic event common to all histological subtypes of salivary gland carcinomas, but carcinoma ex-pleomorphic adenoma. In an attempt to characterize at the molecular level the frequency and the extension of 6q deletions in salivary gland carcinomas, we have investigated the loss of heterozygosity (LOH) at 6q in a series of 13 salivary gland carcinomas, using polymorphic DNA markers. Frozen tumor samples and the normal tissue from each patient were studied by Southern blotting and dinucleotide repeats analysis, using 13 polymorphic markers (1 at 6p, 1 centromeric, and 11 at 6q). All cases were informative for at least one <i>locus</i> at 6q. LOH was observed in 5 cases, all of them showing different histology. The highest frequency of LOH was found at <i>locus</i> D6S37 (2/6 cases) at 6q26-27. The patterns observed were compatible with terminal deletions in 3 cases and interstitial deletions in 2. Furthermore, the data suggests the existence of two distinct regions of LOH at 6q in salivary gland carcinomas. In summary, LOH al 6q was found in 38% of the cases in this series of salivary gland carcinomas. Our results support the assumption that loss of genetic material at 6q is a frequent and probably an important event in salivary gland carcinogenesis. <b>Acknowledgments</b> L.Q. was supported by the Junta Nacional de Investigação Científica c Tecnológica (JNICT). Probes p308 and phMnSOD4 were kindly provided by Prof. E. W. Jabs, and G. I. Bell, respectively.