DNA content in malignant salivary gland tumours

Objective:  Our aim was to evaluate the DNA content in malignant salivary gland tumours using image cytometry and its possible relationships with clinical and morphologic findings, disease course and prognosis.
Patients and methods:  The study sample comprised 31 patients diagnosed and treated for primary malignant salivary gland tumours. Formalin-fixed, paraffin-embedded surgical specimens of all patients were Feulgen-stained for DNA content analysis by image cytometry. Statistical analysis was used to investigate possible relationships between DNA content variables and clinical and histological findings, disease course and patient survival.
Results:  Seventeen (55%) cases of our sample were graded as DNA diploid, four (13%) as DNA aneuploid and 10 (32%) as DNA multiploid. In 15 (48%) cases, the 5c exceeding rate (5cER) was higher than 1.7%. DNA ploidy correlated with N stage and tumour size. DNA ploidy and 5cER had a statistically significant prognostic influence on overall and disease-free survival in univariate analysis. However, in multivariate analysis, stage classification was the only parameter with an independent prognosis value.
Conclusion:  Abnormal DNA content is a common finding in salivary gland cancers. Our results suggest an important role of DNA content analysis in the evaluation of these tumours.     

Pharmacodiagnostic evaluation of EGFR expression in oral squamous cell carcinoma

OBJECTIVE: To determine epidermal growth factor receptor (EGFR) expression in oral squamous cell carcinomas (OSCC), and its possible relationships with clinical findings, histological findings, disease course and prognosis. MATERIALS AND METHODS: Surgical specimens of 47 OSCCs were studied immunohistochemically for detection of EGFR using a standardized immunohistochemical detection system (EGFR PharmaDx kit). Statistical analysis was used to investigate possible relationships between EGFR expression and clinical findings, histological findings, cell proliferation (MIB1 labelling index), disease course and patient survival. RESULTS: Epidermal growth factor receptor expression was absent or weak in 12 cases (25.5%) and moderate or intense in 35 cases (74.5%). However, EGFR expression did not show statistically significant associations with any of the clinical, histological, biological or prognostic variables considered. CONCLUSION: First, despite previous suggestions that EGFR is a useful indicator of biological tumour behaviour, the present results suggest that EGFR is not a useful indicator of prognosis in OSCC. Secondly, the high prevalence of EGFR overexpression suggests that the possibility of anti-EGFR therapy in OSCC merits further investigation.     

Expression of Mcm-2, Ki-67 and geminin in benign and malignant salivary gland tumours

Background:  Recent studies have proposed that minichromosome maintenance (Mcm) proteins may be sensitive proliferation markers and may serve as novel biomarkers for prognostication and diagnosis of various pre-malignant and malignant lesions. The aims of this study were to determine the expression of Mcm-2, Ki-67 and geminin in salivary gland (SG) tumours, and to evaluate their usefulness for diagnosis or for prediction of tumour behaviour.
Methods:  Tissue from 62 SG tumours was assembled in tissue microarray format. There were 13 adenoid cystic carcinomas (ACC), 10 carcinoma ex pleomorphic adenomas (CEPA), 10 mucoepidermoid carcinomas (MEC), 10 polymorphous low-grade adenocarcinomas (PLGA), 10 pleomorphic adenomas (PA) and nine acinic cell carcinomas (AcCC). Clinicopathological data were collected retrospectively and immunohistochemical analyses of Mcm-2, Ki-67 and geminin were performed on all lesions. Labelling index (LI) for each marker was determined by counting the percentage of positive cells in six random fields from three arrays per case.
Results:  Mcm-2 expression was higher than Ki-67 and geminin in all tumours studied. Mcm-2 LI was higher in ACC (28.2 ± 19.2%) than in CEPA, AcCC, MEC, PA and PLGA (5.3 ± 4.1%, P  = 0.001). Mcm-2 LI was higher in CEPA (20.4 ± 5.0%) than in PA (6.9 ± 5.0%, P  = 0.001). LI did not correlate to tumour grade or outcome for any of the markers or tumour types.
Conclusions:  The findings suggest that Mcm-2 may be a sensitive proliferation marker in SG tumours and may be useful for differential diagnosis between PA and CEPA, and ACC and PLGA. Further studies are warranted to assess the value of Mcm-2 as a predictor of recurrence and survival.     

Malignant salivary gland tumours: treatment outcomes from a tertiary referral centre in the UK

Salivary gland malignant tumours are a complex and highly variable pathological group. Their diagnosis can be challenging, and management is guided by multidisciplinary teams. This project aimed to establish clinicopathological and sociodemographic features that significantly impacted overall disease-free or progression-free survival in patients diagnosed with malignant salivary gland disease between 2010 and 2019 in a tertiary referral centre. In total, 86 patients were included for analysis, with a female:male gender ratio of 1.3:1. Mean age at diagnosis was 57.7 years. Mucoepidermoid carcinomas constituted almost 25% (n = 20) of all cases, with adenoid cystic carcinomas (20%, n = 17) and acinic cell carcinomas (17.5%, n = 15) being the next most frequently diagnosed. The parotid gland was the most frequently affected site (80.2%, n = 69). Perineural and lymphovascular invasion, and a maximum tumour dimension of ≥4 cm were highly associated with the decision to provide a neck dissection as part of treatment. Involved margins, extracapsular spread, and lymphovascular and perineural invasion were associated with the need for adjuvant treatment. However, no factors remained statistically significant on multivariate analysis. This retrospective service evaluation demonstrates the difficulty of predicting treatment outcomes for patients diagnosed with malignant salivary gland disease.     

EGFR和C-erbB-2在涎腺肿瘤中的表达及其意义

目的:研究EGFR和C-erbB-2在涎腺肿瘤中的表达,探讨两者之间的关系及临床意义.方法:应用免疫组化S-P法检测EGFR和C-erbB-2在70例涎腺肿瘤中(30例良性肿瘤,40例恶性肿瘤)的表达情况.结果:在口腔涎腺恶性肿瘤组织中,EGFR蛋白的阳性表达率为67.5%(27/40),高于口腔涎腺良性肿瘤组织的43.3%(13/30)(p＜0.05):C-erbB-2蛋白的阳性表达率为33.3%(10/30),显著高于口腔涎腺良性肿瘤组织的6.7%(2/30)(p＜0.05).C-erbB-2与EGFR蛋白表达两者呈显著正相关(r=665,p＜0.01).结论:C-erbB-2与EGFR同时过度表达,可为涎腺肿瘤早期诊断、治疗及判断预后提供依据.     

Salivary duct carcinoma in major and minor salivary glands. A clinicopathological analysis of four cases

Salivary duct carcinomas are an uncommon but distinct group of highly malignant salivary gland tumours. We report the clinical course, pathological findings and surgical treatment of this tumour in 4 patients. In one patient an intraductal tumour developed in a minor salivary gland, while in the other three patients, a major salivary gland was involved by an infiltrating salivary duct carcinoma. We point out the highly aggressive biological behaviour of the tumour when occurring in the major salivary glands, in contrast to the benign course of the intraductal carcinoma in the minor salivary gland.     

Current concepts in research related to oncogenes implicated in salivary gland tumourigenesis: a review of the literature

Background:  Salivary gland tumours are relatively uncommon and there exists considerable difficulty in decisions regarding prognosis and management, as well as diagnostic uncertainty that has implications for treatment.
Method:  Literature pertaining to individual oncogenes has been reviewed and commented upon, specifically looking at the role of these as diagnostic and prognostic markers and as potential targets for treatments.
Results:  kit , PLAG1, Mect1-Maml2 , HMGIC, HER2/ neu , ras , c-fos and Sox-4 all have seminal small-scale studies in the literature with potential for further research and eventual clinical applications.
Conclusion:  A wide variety of oncogenes are implicated in salivary gland tumourigenesis, with evidence being confined to small murine or in vitro studies more often than not. There are possible roles for different oncogenes in therapeutics, prognosis and management of specific salivary gland tumours.     

HER family receptors expression in squamous cell carcinoma of the tongue: study of the possible prognostic and biological significance

J Oral Pathol Med (2010) 39 : 79–86
Objectives:  The squamous cell carcinoma of the tongue (SCCT) is biologically and epidemiologically distinct from other oral cavity cancers and is associated with lower overall survival rates. The role of HER family members (HER-1, HER-2/ neu , HER-3 and HER-4) in the pathogenesis and progression of head and neck squamous cell carcinomas has been demonstrated but no report have focused on SCCT. This study investigated, the expression of all members of the HER family, in a series of SCCT and studied the possible prognostic value and correlation with various clinico-pathological parameters.
Methods:  HER-1, HER-2/ neu , HER-3 and HER-4 expression was analysed by semi-quantitative immunohistochemical staining on paraffin embedded tissue specimens from 40 patients who underwent surgery for SCCT between 1996 and 2006.
Results:  HER-1 was overexpressed in 26 cases (65%), HER-2/ neu in two (5%), HER-3 in 19 (48%) and HER-4 in three cases (8%). No significant correlation was found between clinicopathological variables and expression of HER-1 and HER-2/ neu . HER-3 overexpression was significantly related to nodal stage, age (≥64 years) and decreased overall survival ( P  ≤ 0.05). HER-4 overexpression was significantly associated with low histological grade including when it was coexpressed with HER-3 but in this case the prognosis was worse ( P  < 0.05).
Conclusions:  These results suggest that HER-1 and HER-2/ neu when determined with stringent criteria are not useful indicators of prognosis in SCCT. Only HER-3 overexpression may help in identifying SCCT with greater malignant potential also when it is coexpressed with HER-4. Instead, as in other malignancies, HER-4 could play a protective role in SCCT.     

1878例涎腺肿瘤WHO组织病理学新分类的统计分析

目的 根据ＷＨＯ１９９０年涎腺肿瘤组织病理学新分类标准对１８７８例涎腺肿瘤及肿瘤样疾病进行重新分类,并重点对涎腺上皮性肿瘤的临床发病情况进行统计分析。方法 统计描述。结果 １８７８例涎腺肿瘤以诞腺上皮性肿瘤为主,为１４３１例,占７６．２０％,其中腺瘤发病居首位,其次是涎腺癌,涎腺肿瘤样疾病居第三位;多形性腺瘤是涎腺肿瘤中最常见者,恶性多形性腺瘤为最常见的涎腺癌,特别注意了腺癌亚分类中的几种少见类型     

人涎腺腺样囊性癌中表皮生长因子受体的表达及意义

目的:研究表皮生长因子受体(EGFR)在人涎腺腺样囊性癌组织和细胞系中的表达及其临床病理学意义。方法:采用免疫组化S-P法对86例不同亚型的人涎腺腺样囊性癌组织病理切片、20例正常腮腺组织切片及ACC-2细胞爬片进行EGFR的检测;激光共聚焦显微镜对ACC-2细胞中EGFR的表达情况进行检测。结果:在涎腺腺样囊性癌组织中EGFR呈过度表达,其阳性率要明显高于正常腮腺组织(P<0.05);EGFR的表达在腺样囊性癌的恶性程度相关(P<0.05);ACC-2细胞中也检测到了EGFR的过度表达。结论:EGFR表达与腺样囊性癌恶性度及预后密切相关。     

A clinico-pathologic study of 311 intra-oral salivary gland tumors in Thais

Background:  There have been several epidemiologic studies on intra-oral salivary gland tumors in several countries, but little is known of these tumors in Thailand.
Objectives:  To determine the relative frequency and distribution of various types of intra-oral salivary gland tumors in the Thai population.
Methods:  The files of the Department of Oral Pathology, Faculty of Dentistry, Chulalongkorn University, from 1969 to 2007 were searched for intra-oral salivary gland tumors. Histopathologic slides were reviewed and reclassified according to the 2005 WHO Classification of Head and Neck Tumors. The age, gender, race, and anatomical distribution of the tumors were collected from the patients' records.
Results:  Of the 16,358 accessioned cases, 311 cases (1.90%) were diagnosed as intra-oral salivary gland tumors. One hundred and forty-seven cases (47.27%) were benign tumors, while 164 cases (52.73%) were malignant tumors. The mean age of the patient ± SD = 41.57 ± 16.65 years. Females outnumbered male patients by a ratio of M:F = 1:1.38. Almost all except one patient were Thais. Pleomorphic adenoma was the most common intra-oral salivary gland tumor. The majority of cases occurred at the palate.
Conclusions:  Pleomorphic adenoma is the most common intra-oral salivary gland tumor and the most common benign intra-oral salivary gland tumor, while mucoepidermoid carcinoma is the most common malignant intra-oral salivary gland tumor. Intra-oral salivary gland tumors in Thailand elicit similar trend as in previous studies, with only minor differences such as the ranking of some tumors, the higher incidence of intra-bony location, and the lower incidence of polymorphous low-grade adenocarcinoma.     

Epithelial salivary gland tumors of children and adolescents in west China population: a clinicopathologic study of 79 cases

Objective:  Determine the clinical and histopathologic features of epithelial salivary gland tumors of children and adolescents.
Methods:  A total of 79 cases of epithelial salivary gland tumors of children and adolescents were retrieved from the files. Information about demographic, clinical, histopathologic characteristics, and follow-up status were analyzed.
Results:  Sixty tumors (75.9%) were benign and 19 (24.1%) malignant. The most common tumor overall was pleomorphic adenoma (PA). The parotid was the most frequently involved site (43.0%). PA was the most common type of benign tumor. The most common malignant tumor was mucoepidermoid carcinoma. Five patients with parotid PA and two cases with palate myoepithelioma showed local recurrences. One patient with mucoepidermoid carcinoma showed local recurrences and died from the tumor 3 years after the initial treatment. One patient with adenocarcinoma presented local and neck recurrences, and died 4 years after initial treatment.
Conclusions:  Our data showed that the salivary gland tumors in children and adolescents may be the higher incidence of benign tumors, especially of PA; the slightly higher tendency for female predominance; the higher incidence of parotid glands. Mucoepidermoid carcinoma was the most common malignant tumor, with majority of low grade. Initial treatment should be planned to excise the tumor completely with satisfactory margins. The neck dissections or postoperative radiotherapy were performed in patients with low differentiation malignancies, or patients who present nodal metastasis or with clinically suspicious regional metastasis.     

Migration‐stimulating factor as a novel biomarker in salivary gland tumours

J Oral Pathol Med (2011) 40 : 747–754 Background: The identification of novel stratification biomarkers would benefit the clinical management of patients with salivary gland tumours. Migration‐stimulating factor (MSF) is a potent stimulator of cell invasion, matrix remodelling and angiogenesis. The aim of this study was to determine whether MSF was expressed in salivary gland tumours and its potential value as a diagnostic biomarker. Methods: Paraffin‐embedded archival specimens of small salivary gland tumours were stained with an MSF‐specific antibody. The specimens included 27 malignant and seven benign tumours; histologically normal salivary gland adjacent to the tumour was present in 16 specimens. MSF expression was assessed by consensus of 2–4 independent observers according to various indices, including ‘overall MSF grade’, ‘percentage of area stained’ and ‘intensity of the staining’. The motogenic effect of MSF on a salivary gland tumour cell line, HSG, was examined in the transmembrane assay. Results: Overall MSF expression increased significantly in a step‐wise fashion from normal salivary gland to benign and malignant tumours (P = 0.04–0.0001); with moderate/strong positive specimens representing 6%, 33% and 74% of the normal, benign and malignant specimens, respectively. MSF was heterogeneously expressed in both carcinoma and stromal cell compartments, its expression being higher in malignant than benign tumours regarding various MSF indices. In tissue culture studies, exogenous MSF stimulated the migration of HSG cells. Conclusions: These immunohistochemical and functional studies suggest that MSF expression is a potentially useful biomarker of salivary gland tumour progression.     

Expression of vascular endothelial growth factor in salivary gland carcinomas and its relation to p53, Ki-67 and prognosis

BACKGROUND: Vascular endothelial growth factor (VEGF) has been demonstrated to play an important role in tumor angiogenesis and to influence prognosis in many cancers. But, its significance in salivary gland carcinomas has not been elucidated. The authors investigated the association between VEGF expression and clinicopathological factors, p53, and Ki-67 to verify its validity as a prognostic factor. METHODS: Surgical specimens from 45 patients with salivary gland carcinoma were examined for VEGF, p53, and Ki-67 expression by immunohistochemical staining. The results were compared with the clinicopathological factors and the relationships were correlated. RESULTS: VEGF expression was low in 14 cases, moderate in 15 cases, and high in 16 cases. It was significantly correlated with a variety of clinicopathological factors such as TNM stage, perineural and vascular invasion, and recurrence. VEGF showed significant association with the expression of p53 but not with that of Ki-67. Univariate analysis showed that age, gender, lymph node metastasis, vascular invasion, p53, Ki-67, and VEGF expression correlate with prognosis. Multivariate analysis demonstrated that VEGF is an independent prognostic factor for patients with salivary gland carcinomas. CONCLUSIONS: The results of this study suggest that VEGF expression is correlated with p53 expression and that it may have prognostic value in salivary gland carcinomas.     

The role of bronchoscopy and gastroscopy in intraoral minor salivary gland carcinomas at initial staging

Intraoral minor salivary gland carcinomas are rare tumours the incidence, distribution, and prognostic factors of which differ. The prognosis of patients depends on the presence of metastases or synchronous malignant diseases that usually affect the lungs. The incidence of metastases has been reported to be about 9% at the time of primary staging. The aim of this study was to assess the value of bronchoscopy and gastroscopy in the routine staging of minor salivary gland cancers.     

Maspin蛋白在唾液腺黏液表皮样癌中的表达及意义

目的：检测乳腺丝氨酸蛋白酶抑制剂（marray serine proteinase inhibitor，Maspin）在唾液腺黏液表皮样癌中的表达．及其与唾液腺黏液表皮样癌患者临床病理特征之间的关系。方法：应用免疫组织化学方法，分别对58例唾液腺黏液表皮样癌的癌组织及其癌旁正常腺体组织标本行Maspin蛋白含量的半定量测定，与各临床病理指标进行统计学分析，采用SPSS13．0统计学软件进行非参数检验。结果：Maspin蛋白在唾液腺黏液表皮样癌的癌组织中的表达显著高于癌旁正常腺体组织（P〈0．001），唾液腺黏液表皮样癌组织中Maspin蛋白的表达与淋巴结转移（P=0．020）、术后转移（P=0．008）呈负相关，与总体生存状况呈正相关（P=0．028）。结论：Maspin蛋白的检测在唾液腺黏液表皮样癌患者中可能具有较好的预后判断价值。     

唾液腺肿瘤中survivin mRNA水平与临床病理的关系

目的：探讨唾液腺肿瘤中survivin mRNA的表达及其与唾液腺肿瘤发生、发展以及临床病理的关系。方法：制备组织芯片,应用原位杂交技术检测良、恶性唾液腺肿瘤组织以及周边腺组织中的survivin mRNA表达。采用SPSS10．0统计软件包进行x^2检验和秩和检验。结果：Survivin mRNA的表达在唾液腺良、恶性肿瘤中有显著差别（P〈0．05）;在癌旁腺体与恶性肿瘤中的表达无显著差异（P〉0．05）。在恶性肿瘤中,高分化组与中、低分化组、淋巴结转移组与未转移组、复发瘤与原发瘤间均存在显著差异fP〈O．05）;在不同性别、年龄以及不同大小肿瘤间均无显著差异（P〉0．05）。结论：Survivin mRNA的表达与唾液腺恶性肿瘤的临床病理有关,可作为唾液腺恶性肿瘤早期诊断及预后判断的可靠指标。     

Prognostic factors in primary salivary gland mucoepidermoid carcinoma: an analysis of 376 cases in an Eastern Chinese population

Mucoepidermoid carcinoma (MEC) is an infrequent malignant neoplasm that originates most commonly in the salivary glands. The present study aimed to provide new information on prognostic factors in patients with salivary gland MEC. A retrospective analysis of the medical records of patients diagnosed with primary salivary gland MEC between 2003 and 2010 was conducted. The incidence of MEC in the minor salivary glands (62.2%) was almost twice that in the major salivary glands (37.8%). The most frequently affected sites were the parotid gland and palate. Lymph node metastasis was reported more frequently in male than female patients (P = 0.02), in high-grade than low/intermediate grade lesions (P < 0.001), and in lesions involving the submandibular gland (P < 0.001). The disease-free survival (DFS) at 5 years was 80.47%, with rates of 98.0%, 86.5%, and 38.5% for low-, intermediate-, and high-grade tumours, respectively. Among various clinicopathological factors, the only independent prognostic factor was histological grade (P < 0.001). Primary tumour site and histological grade are two important factors affecting cervical lymph node metastasis. Histological grade is the only independent factor affecting survival beyond tumor lymph node metastasis (TNM) staging in salivary gland MEC. Further advances in therapy are needed to improve the outcomes for patients with high-grade lesions.     

MutSα expression predicts a lower disease-free survival in malignant salivary gland tumors: an immunohistochemical study

Background Appropriate DNA replication is vital to maintain cell integrity at the genomic level. Malfunction on DNA repair mechanisms can have implications related to tumor behavior. Our aim was to evaluate the expression of key complexes of the DNA mismatch-repair system MutSα (hMSH2-hMSH6) and MutSβ (hMSH2-hMSH3) in a panel comprising the most common benign and malignant salivary gland tumors (SGT), and to determine their association with disease-free survival.Material and Methods Ten cases of normal salivary gland (NSG) and 92 of SGT (54 benign and 38 malignant) were retrieved. Immunohistochemistry was performed for hMSH2, hMSH3, hMSH6. Scanned slides were digitally analyzed based on the percentage of positive cells with nuclear staining. Cases were further classified in MutSαhigh and MutSβhigh based on hMSH2-hMSH6 and hMSH3-hMSH6 expression, respectively.Results hMSH3 expression was lower in malignant SGT compared to NSG and benign cases. Adenoid cystic carcinoma (ACC) cases with perineural invasion presented a lower percentage of hMSH3 positive cells. hMSH6 was downregulated in both benign and malignant SGT compared to NSG. Malignant SGT cases with MutSαhigh expression had lower disease-free survival compared to MutSαlow cases. A 10.26-fold increased risk of presenting local recurrence was observed.Conclusions Our findings suggest that a lack of hMSH3 protein function is associated with a more aggressive phenotype (malignancy and perineural invasion) and that MutSα overexpression predicts a poor clinical outcome in malignant SGT. Key words:Salivary Gland Neoplasms, salivary gland cancer, DNA-repair, biomarkers, prognosis.     

Expression and mutations of p53 in salivary gland tumours

A series of 219 salivary gland tumours (103 carcinomas and 116 benign tumours) were analysed for p53 protein expression using immunohistochemistry, and for mutations in p53 gene using non-radioactive single strand conformation polymorphism (SSCP). p53 expression was present in 36% (42/116) of the benign tumours and in 54% (56/103) of the carcinomas. The highest prevalence of p53 expression was found in adenoid cystic carcinomas (69%). followed by mucoepidermoid carcinomas (67%). Of the benign tumours, pleomorphic adenomas showed the highest prevalence of p53 positivity (41%). In malignant tumours, expression of p53 bore no correlation to local recurrence, metastatic disease or survival of the patients. Exons 5 through 9 were analysed and four mutations were found in 20 cases of p53-immunopositive tumours and two in 20 p53-negative tumours. Each of the exons 5.6 and 8/9 had two mutations, whereas no mutations were detected in exon 7.