Humans ; Adenoma, Pleomorphic/genetics* ; Adenoma ; Salivary Gland Neoplasms/genetics* ; Adaptor Proteins, Signal Transducing

OBJECTIVEThis study aimed to investigate the expression of midkine (MK) and microvessel density (MVD) in patients with salivary adenoid cystic carcinoma (SACC) and its clinical significance, as well as detect the correlation between the expression of MK and MVD in SACC.

METHODSImmunohistochemistry analysis (SP method) for MK and MVD were performed on 60 cases of SACC and 26 cases of normal salivary gland tissue. The expression of MK and MVD, as well as the correlation between the expression of MK and MVD in SACC were detected.

RESULTSIn SACC, the MK expression rate was 70.0% (42/60), and MK was not expressed in normal tissue. Statistical significance was found between SACC and normal tissue (P<0.05). The MVD values in SACC and normal salivary gland tissues were 38.73 +/- 8.96 and 11.15 +/- 3.33, respectively. These values were statistically significant (P<0.05). The expression levels of MK and MVD were unrelated to age, gender, and type in SACC (P>0.05), but correlated with tumor size, lymph node metastasis, and tumor-node-metastasis in SACC (P<0.05). The expression of MK and MVD was positively correlated with SACC (r=0.560, P<0.05).

CONCLUSIONSACC is correlated with the expression of MK protein and the increase in MVD, which may be some of the early diagnostic markers in SACC.

Carcinoma, Adenoid Cystic ; enzymology ; pathology ; Cytokines ; genetics ; metabolism ; Humans ; Immunohistochemistry ; Lymphatic Metastasis ; Microvessels ; Nerve Growth Factors ; Salivary Gland Neoplasms ; enzymology ; pathology ; Salivary Glands ; enzymology

OBJECTIVETo study the expression of p16 and nm23 genes in salivary gland tumors and the relation of P16 and nm23 proteins with fumorigenesis of salivary gland tumors.

METHODSExpression of P16 and nm23 proteins was examined by SABC immunohistochemical method in 39 cases of paraffin blocks of normal salivary gland tissues and salivary gland tumors.

RESULTSP16 and nm23 protein positive staining were mainly found in the cytoplasm and cytoblast of all salivary gland tissues. Positive rate of P16 protein expression was 76.9% (10/13) and 40.9% (9/22) in benign and malignant salivary gland tumors, respectively. There was significant difference between P16 protein expression of benign and malignant tumors by chi 2 test (P < 0.05). mm23 protein positive staining was found in 84.6% (11/13) and 45.5% (10/22) of benign and malignant tumors respectively. The expression of nm23 protein in benign and malignant tumors was significantly different (P < 0.05). There was no correlation of the expression of P16 and nm23 in salivary gland tumors was found (P > 0.05).

CONCLUSIONp16 and nm23 genes may play an important role in different sides in salivary gland tumorigenesis and the reduce of the expression of p16 and nm23 genes may contribute to the generation of malignant salivary gland tumors.

Adenoma, Pleomorphic ; genetics ; metabolism ; Carcinoma, Mucoepidermoid ; genetics ; metabolism ; Cyclin-Dependent Kinase Inhibitor p16 ; biosynthesis ; genetics ; Humans ; Immunohistochemistry ; NM23 Nucleoside Diphosphate Kinases ; Nucleoside-Diphosphate Kinase ; Protein Biosynthesis ; Proteins ; genetics ; Salivary Gland Neoplasms ; genetics ; metabolism ; Salivary Glands ; metabolism

OBJECTIVETo investigate the evolution pattern of the Runx3 gene 5'-CpG island ~3478 bp region methylation in human salivary gland adenoid cystic carcinoma (SGACC).

METHODSQuantitative MSP method was used to detect the methylation status of CpG island in various regions (No.1-10) of Runx3 promoter region, and Western blot was used for detection of the expression of Runx3 protein in 41 salivary gland SGACC samples and corresponding non-neoplastic salivary gland tissues. A Logistic model was used to analyze the risk ratio between the methylation status of CpG island in Runx3 gene and development of salivary SGACC, meanwhile, the possible association among the methylation of Runx3 gene, the clinicopathological parameters of SGACCs, and Runx3 protein expression was compared.

RESULTSThe results of qMSP showed that the hypermethylation initially occurred at the most 5' region of the Runx3 CpG island and spread to the transcription start site. The methylation rate was highest in region No. 1 and No. 2 among the successive ten regions ranging from the 5' region to the transcription start site within the Runx3 CpG island, and lowest in the transcription start site both in SGACCs and normal salivary glands. Furthermore, there was no methylation in the transcription start site in nomal salivary glands tissues. Together with the results of Logistic model analysis, those results indicate that the transcription start site within the Runx3 promoter CpG island is critical for gene silencing. Western blot results revealed that the Runx3 protein level in SGACC was significantly lower than that in normal salivary glands (P < 0.01). In combination of the results of qMSP, it is presumed that the Runx3 gene methylation is one of the reason inducing the down-regulation of Runx3 in SGACCs.

CONCLUSIONSMethylation of the Runx3 CpG island spreads from the most 5'-region to the transcription start site in human salivary gland adenoid cystic carcinoma, and the transcription start site may be a critical region for the methylation of Runx3. The evolution pattern of Runx3 gene methylation is related to the tumorigenesis of SGACCs.

Adult ; Aged ; Aged, 80 and over ; Carcinoma, Adenoid Cystic ; genetics ; metabolism ; pathology ; Core Binding Factor Alpha 3 Subunit ; genetics ; metabolism ; CpG Islands ; genetics ; DNA Methylation ; Female ; Humans ; Logistic Models ; Male ; Middle Aged ; Salivary Gland Neoplasms ; genetics ; metabolism ; pathology ; Salivary Glands ; metabolism

OBJECTIVETo analyze the original mutated codon of p53 gene of salivary pleomorphic adenoma (SPA) and to evaluate the repair effects of wt-p53 on SPA cells.

METHODSFour cases of SPA were obtained from clinical fresh samples and SPA cells were separated and cultured, and then the cells were transduced by Ad-wt-p53. The cells and the corresponding tumor tissue DNA were extracted, PCR and single strand conformational polymorphism (SSCP) and DNA sequencing analysis were performed.

RESULTSPCR-SSCP analysis showed 3 out of 4 SPA with abnormal exon 8 and abnormal exon 6. DNA sequencing analysis showed that exon 6 point mutation was found at codon 203 (GTG-->GCG), poly-codon mutations were found in exon 8 at codon 272 (GTG-->GT square), 275 (TGT-->T square T), 276 (GCC--> square CC) and at codon 290 (CGC-->CGCC). After transduced by Ad-wt-p53, all of the mutated codons were repaired.

CONCLUSIONSp53 gene mutation involved many codons that occurred frequently in the tumorigenesis of SPA. Exogenous wt-p53 could compensate and repair all the mutated p53 codons of SPA cells. SPA cells transduced by Ad-wt-p53 showed the typical apoptosis.

Adenoma, Pleomorphic ; genetics ; DNA Repair ; Humans ; Mutation ; Polymorphism, Single-Stranded Conformational ; Salivary Gland Neoplasms ; genetics ; Transfection ; Tumor Cells, Cultured ; Tumor Suppressor Protein p53 ; genetics

OBJECTIVETo determine at the mRNA level whether the MAGE-A1 and -A3 genes are expressed in cancer cell lines from salivary glands and relevant clinical carcinomas, and thus to distinguish cancerous tissues from normal tissues and benign tumors in salivary glands.

METHODSThe expression of the MEGE-A1 and MEGE-A3 genes at the mRNA level was determined by reverse transcription and polymerase chain reaction (RT-PCR) in 2 cell lines of human adenoid cyst carcinomas (ACC-2 and ACC-M), in 18 malignant tumors and 9 benign salivary gland tumors, and in 10 samples of normal salivary gland tissues.

RESULTSBoth MAGE-A1 and -A3 genes were expressed in ACC-2 and ACC-M cell lines. None of the 9 benign tumors or the 10 normal tissue samples of salivary glands expressed the genes. The MAGE-A1 and -A3 genes were expressed in 9 (50%) and 11 (61%) of 18 salivary gland carcinomas, respectively, and at least 1 of the 2 genes was expressed in 14 (78%) of them. Of the 18 salivary gland carcinomas, 6 low-differentiated carcinomas (33%) expressed both genes, whereas 4 high-differentiated carcinomas (22%) expressed neither gene.

CONCLUSIONSThe MAGE-A1 and -A3 genes can be expressed in cancer cell lines of salivary glands and relevant clinical carcinomas in addition to other malignant tumors of various histological origins. The results suggest the possibility of immunotherapy against salivary gland carcinomas by using MAGE-gene-encoded products as target antigens for tumor-rejection.

Adult ; Aged ; Antigens, Neoplasm ; genetics ; Female ; Gene Expression ; Humans ; Male ; Melanoma-Specific Antigens ; Middle Aged ; Neoplasm Proteins ; genetics ; Salivary Gland Neoplasms ; genetics ; metabolism ; Tumor Cells, Cultured

OBJECTIVETo study the expressions of matrix metalloproteinase 2 (MMP2) and E-cadherin (E-CD) in salivary mucoepidermoid carcinoma, and their relationship with clinical stages, pathological grading, lymph node metastasis and prognosis.

METHODSSurgical specimens of salivary mucoepidermiod carcinoma and normal salivary gland tissue were collected. MMP-2 and E-CD were stained immunohistochemically with streptavidin peroxidase method.

RESULTSThe expression of MMP-2 was increased and the expression of E-CD was reduced or negative in salivary mucoepidemoid carcinoma compared with those of the normal salivary gland. Expression of MMP-2 and E-CD was closely correlated with lymph node metastasis of the mucoepidermoid carcinoma. MMP-2 was positively correlated with the prognosis of mucoepidermoid carcinoma, and E-CD was negatively correlated to the prognosis of mucoepidermoid carcinoma.

CONCLUSIONThe expression of MMP-2 and E-CD is closely correlated with the metastasis and prognosis of salivary mucoepidermoid carcinoma.

Cadherins ; biosynthesis ; genetics ; Carcinoma, Mucoepidermoid ; metabolism ; pathology ; Humans ; Matrix Metalloproteinase 2 ; biosynthesis ; genetics ; Neoplasm Invasiveness ; Neoplasm Metastasis ; Prognosis ; Salivary Gland Neoplasms ; metabolism ; pathology

Objective: To investigate the clinical and pathological features of salivary secretory carcinoma (SSC). Methods: Ten cases of SSC confirmed in the Department of Pathology,Capital Medical University School of Stomatology from January 2014 to December 2021 were retrospectively included, including 5 males and 5 females, with a median age of 46.5 years. The microscopic morphology, immunophenotype, special staining and clinical follow-up of 10 cases of salivary secretory carcinoma were observed. Ten patients were tested with S-100, vimentin, mammaglobin, Dog-1, p63 and Ki-67, 9 cases with cytokeratin (CK) 8/18, 8 with CK7, 6 with calponin, 5 with smooth muscle actin (SMA) and GCDFP15, 4 with CK5/6 and 1 with SOX10. The ETV6-NTRK3 fusion gene was detected by fluorescence in situ hybridization. Results: Seven of the 10 SSC were located in the parotid gland and 3 were located in the cheeks. Histomorphology showed solid, papillary-cystic, follicular, microcystic, and macrocystic types. In 7 cases, tumor cells were dominated by single arrangement type, while certain mixed arrangements existed in some areas. The cytoplasm of the tumor cells was rich in eosinophilic, fine granular or vacuolar shapes, and clear cytoplasm was seen in 2 cases. The nuclei were mostly oval-shaped vesicular nuclei, with nucleoli in the center. Immunohistochemistry showed CK7 (8/8) positive, CK8/18 (9/9) positive, S-100 (10/10) positive, vimentin (5/10) positive, (4/10) partially positive and (1/10) less partially positive, mammaglobin (7/10) positive, (1/10) partially positive and (2/10) some individual cells positive, Dog-1 (10/10) negative, CK5/6 (4/4) negative, p63 (7/10) negative and (3/10) partially positive, SMA (5/5) negative, calponin (6/6) negative, and Ki-67 index was 5%-20%. Secretions of 5 cases showed periodic acid-Schiff (PAS) and PAS with diastase (PAS-D) staining positive. All 10 cases showed ETV6-NTRK3 fusion positive. Six cases were successfully followed up for 32-91 months, of which 2 cases recurred after 28 and 74 months and underwent surgical resection again. All cases followed up are alive and disease-free. Conclusions: The salivary secretory carcinoma is a rare low-grade malignant tumor. In certain cases, morphology is atypical and mammaglobin is immunohistochemically positive in only individual tumor cells. Therefore, the diagnosis should be supported with morphology, immunohistochemical staining, and molecular feature preferably.
Female ; Male ; Biomarkers, Tumor ; Carcinoma/pathology* ; In Situ Hybridization, Fluorescence ; Ki-67 Antigen/genetics* ; Neoplasm Recurrence, Local ; Retrospective Studies ; S100 Proteins ; Salivary Gland Neoplasms/pathology* ; Vimentin

Objective: To study the clinicopathologic and genetic features of papillary cystic low-grade mucoepidermoid carcinoma (LG-MEC) and cystadenoma. Methods: A retrospective review was performed on salivary gland tumor patients with papillary cystic architecture who presented to department of oral pathology, Peking University School and Hospital of Stomatology between January 2010 and June 2022. Among this cohort, there were 17 males and 17 females with a range age of 23-82 years [(55.6±14.6) years]. Diagnosis was confirmed by histological, immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) analysis. Finally, 15 papillary cystic LG-MEC and 19 cystadenoma patients were included in the present study. All patients were followed clinically and radiologically, and the duration of follow-up ranged from 1 to 141 months. Results: All neoplasms showed papillary proliferation with multilocular or giant cystic tumors. Papillary cystic LG-MEC was characterized by epidermoid cells, intermediate cell and mucous cells with multiple lining-layers. Papillary cystic LG-MEC had mild cellular atypia and a pushing infiltration. Cystadenoma was characterized by cuboidal, columnar and ciliated pseudostratified columnar lining epithelium. Squamous metaplasia, mucinous metaplasia and acidophilic degeneration could also be observed focally in cystadenoma. For IHC staining, papillary cystic LG-MEC showed diffusely and strongly positive for mucin 4 (MUC4) (15/15) and mucin 5 Subtype AC (MUC5AC) (4/15) in the epidermoid cells, intermediate cell and mucous cells. The epidermoid cells and intermediate cells were diffusely positive for p40 and p63. The Ki-67 index was about 10%-15% in LG-MEC. As a contrast, p40 (17/19) and p63 (14/15) were only detected in the basal cells of cystadenoma. Cystadenoma showed focal MUC5AC (4/19)expression and MUC4 (19/19)diffuse expression. In addition, the Ki-67 index was 5%-10% in cystadenoma. The MAML2 gene translocation was detected in 11 LG-MEC patients, but none in cystadenoma. Conclusions: The differential diagnosis points between papillary cystic LG-MEC and cystadenoma included the specific epidermoid cells, intermediate cells and mucus cells in LG-MEC, cell atypia, the pushing-infiltration pattern, diffuse expression of p40 and p63 in the lining epithelium, and a MAML2 gene rearrangement. The molecular test of MAML2 should be recommended to reduce missed LG-MEC diagnoses.
Male ; Female ; Humans ; Carcinoma, Mucoepidermoid/pathology* ; In Situ Hybridization, Fluorescence ; Ki-67 Antigen/genetics* ; Biomarkers, Tumor/analysis* ; Salivary Gland Neoplasms/diagnosis* ; Transcription Factors/metabolism* ; Cystadenoma ; Metaplasia

OBJECTIVETo investigate the expression of p38 mitogen-activated protein kinase (p38MAPK) in salivary adenoid cystic carcinoma (SACC) tissues and their clinicopathologic significance.

METHODSThe protein and mRNA expressions of p38MAPK were examined by immunohistochemistry and in situ hybridization, respectively, in 52 cases of SACC and in 11 normal salivary gland tissues adjacent to the tumors on a tissue microarray platform.

RESULTSThe positive rate of p38MAPK protein expression in the paracancerous normal salivary gland tissues and that in SACC were 36.4% and 96.2%, respectively, showing a significant statistical difference (P < 0.01). The protein expression of p38MAPK was positively correlated with the lymph node metastasis and nerve involvement (P < 0.05). The positive rates of p38MAPK mRNA in the paracancerous tissues and in the SACC tissues were 45.5% and 94.2%, respectively, with a significant statistical difference (P < 0.01). The mRNA expression of p38MAPK was positively correlated with the lymph node metastasis and nerve involvement (P < 0.05). In the SACC, there was a notable positive correlation between the p38MAPK protein and mRNA expressions (r = 0.409, P < 0.01).

CONCLUSIONSThe expression of p38MAPK is up-regulated in salivary adenoid cystic carcinoma. p38MARK may be involved in the tumorigenesis, development and metastasis of this cancer.

Adult ; Aged ; Carcinoma, Adenoid Cystic ; enzymology ; pathology ; Female ; Humans ; Lymphatic Metastasis ; Male ; Middle Aged ; RNA, Messenger ; metabolism ; Salivary Gland Neoplasms ; enzymology ; pathology ; Salivary Glands ; enzymology ; Up-Regulation ; p38 Mitogen-Activated Protein Kinases ; genetics ; metabolism