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Di Palma S, Skálová A, Vanìèek T, Simpson R H W, Stárek I&Leivo I(2005)Histopathology46,144–152Non-invasive (intracapsular) carcinoma ex pleomorphic adenoma: recognition of focal carcinoma by HER-2/ neuand MIB1 immunohistochemistry: Non-invasive carcinoma ex pleomorphic adenoma is defined as a carcinoma arising within the boundaries of a pleomorphic adenoma (PA), but which fails to display invasion beyond the capsule of host PA. Alternative names are intracapsular,in situ, or focal carcinoma. The true nature of non-invasive carcinoma ex-PA is still controversial; for example, it is not clear whether it represents early but genuine carcinomatous changes with the genetic make-up of malignant cells, or simply cytological, possibly metaplastic or‘bizarre’ changes in PA. Strong overexpression and amplification of HER-2/ neuprotein has recently been demonstrated in invasive carcinoma ex-PA. In addition, data from breast cancer studies suggest that amplification of HER-2/neuand overexpression of its gene product is mainly involved in the initiation of breast oncogenesis. We sought to establish whether this method could help to demonstrate that what is described as non-invasive carcinoma ex-PA is really a genuine malignancy, albeit in an early phase.: Eleven cases of non-invasive carcinoma (in situ) ex-PA were studied for HER-2/ neustatus using immunohistochemistry and fluorescentin-situhybridization (FISH). Cells of focal non-invasive carcinoma ex-PA were strongly positive for HER-2/ neuprotein, while the cells of the maternal PA were always negative. Two cases of low-grade non-invasive myoepithelial carcinoma ex-PA were negative. In four cases out of a total of six tumours studied by FISH, we detected amplification ofHER-2/neugene signals in tumour cells of focal, non-invasive, carcinoma.: The current data suggest that non-invasive carcinoma ex PA is a genuine carcinoma within a PA. However, the presence of cyto-nuclear atypia is not sufficient to make a definite diagnosis of malignant change, which requires a combination of morphology and immunohistochemistry. [ABSTRACT FROM AUTHOR]

Aims: Salivary duct carcinoma is a highly malignant salivary gland tumour with aggressive clinical behaviour, characterized by histological resemblance to invasive ductal carcinoma of the breast. Amplification of HER-2/neu oncogene and over-expression of its gene product have both prognostic and therapeutic implications in breast cancer. Recent report on salivary duct carcinomas for HER-2/neu using immunohistochemistry (IHC) has shown over-expression in most cases. However, correlation between IHC and molecular genetic analysis of HER-2/neu in salivary duct carcinoma has not yet been performed. Methods and results: We have now evaluated 11 cases of salivary duct carcinomas for HER-2/neu status using IHC and fluorescent in-situ hybridization (FISH). To our knowledge, this is the first molecular genetic analysis of HER-2/neu in salivary duct carcinoma. Conclusions: In immunohistochemistry, over-expression of HER-2/neu protein was identified as distinct membrane staining in most carcinoma cells in all our salivary duct carcinoma cases, while only four cases revealed an amplification of HER-2/neu gene by means of FISH analysis. Both amplified and non-amplified salivary duct carcinomas with strong immunohistochemical staining for HER-2/neu protein were associated with poor clinical outcome for the patients. Apparently, HER-2/neu protein over-expression could also be controlled by mechanisms other than gene amplification. In the group of salivary gland tumours other than salivary duct carcinoma, strong over-expression was detected only in three cases of carcinoma ex pleomorphic adenoma. Thus, over-expression of HER-2/neu protein is also a useful marker of malignant transformation in pleomorphic adenomas. [ABSTRACT FROM AUTHOR]

Presents abstracts from the 2001 Annual Meeting of the Scandinavian Society for Head and Neck Oncology in Stockholm, Sweden. Human Papilloma Virus, protein p53, TP53 mutations and outcome in stage I squamous cell carcinomas of the oral tongue; ACE-inhibition with Ramipril improves after thoracic irradiation in mice; Treatment in a team of patients with carcinoma of the oral cavity.

Focuses on PTEN and LKB1 genes in laryngeal tumors. Roles of several tumor suppressor genes in human tumors; Underlining of germlike mutations of PTEN and LKB1 on Cowden disease and Peutz-Jerhers syndrome; Evaluation of the role of somatic mutations in PTEN and LKBL genes.

Background: There is lack of knowledge on the utility of prognostic histopathologic characteristics in adenoid cystic carcinoma (ACC) of the head and neck. We evaluated the prognostic value of tumor and stroma-related histopathologic features in ACC., Materials and Methods: A total of 65 cases of ACC from minor and major salivary glands were included in this study. We evaluated tumor budding, tumor-infiltrating lymphocytes (TILs), and tumor-stroma ratio (TSR) in hematoxylin and eosin (HE) stained sections., Results: Stroma-rich ACCs recurred more frequently (p = 0.029) during follow-up and associated with distant metastasis (p = 0.038). In multivariable analysis, stroma-rich tumors associated with poorer disease-specific survival with a hazard ratio of 3.76 (95% CI 1.10-12.83, p = 0.034). ACCs commonly showed a low infiltration of TILs as 89% of the tumors was characterized by an immune desert pattern. Low infiltration of TILs associated significantly with increased tumor budding (p = 0.039)., Conclusion: Adverse features of TSR and tumor budding are widely expressed in ACC, and stroma-rich tumors are associated with poor prognosis. Low number of TILs in ACC tissue indicates a weak immune response by the host and illustrates the nature of ACC as a relentless malignancy., (© 2024 The Author(s). Journal of Oral Pathology & Medicine published by John Wiley & Sons Ltd.)

Background: Adenoid cystic carcinoma (AdCC) and polymorphous adenocarcinoma (PAC) are included among the most common salivary gland cancers. They share clinical and histological characteristics, making their diagnosis challenging in specific cases. MicroRNAs (miRNA) are short, non-coding RNA sequences of 19-25 nucleotides in length that are involved in post-transcriptional protein expression. They have been shown to play important roles in neoplastic and non-neoplastic processes and have been suggested as diagnostic and prognostic markers., Methods: This study, using quantitative RT-PCR, investigated miR-150, miR-455-3p and miR-375 expression, in order to identify a possible molecular distinction between AdCC and PAC., Results: miRNA-150 and miRNA-375 expression was significantly decreased in AdCC and PAC compared with salivary gland tissue controls, whilst miRNA-455-3p showed significantly increased expression in AdCC when compared to PAC, (P < 0.05). miR-150, miR-357 and miR-455-3p expression in AdCC, PAC and control was not associated with age, gender nor with anatomic site (major and minor salivary glands) (P > 0.05)., Conclusion: MiR-455-3p could be used as a complimentary tool in the diagnosis of challenging AdCC cases., (© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Mucoepidermoid carcinoma (MEC) is the most common salivary gland malignancy. Although several biomarkers have been evaluated, histological grade remains the most valuable prognostic marker. Toll-like receptor 9 (TLR9) is an immune receptor recognizing microbial DNA. Its expression associates with prognosis or cancer properties in several cancers. This study examined the role of TLR9 in MEC., Methods: Sixty patients with salivary gland MEC were collected from two Finnish university hospitals, and tumor samples were stained for TLR9. Salivary gland high-grade MEC cell line (UT-MUC-1) was cultured to assess TLR9 and MMP-13 expression. The function of TLR9 was studied in vitro using traditional Matrigel(®) invasion assay and novel human myoma organotypic model., Results: Cancer-specific survival was related with tumor grade (P = 0.01), and there were no deaths in patients with low-grade MEC. TLR9 was expressed in 56 of 60 (93%) tumors. High TLR9 expression indicated better survival in the patient series (P = 0.002) and showed a trend for association with lower disease stage (P = 0.06) and higher differentiation grade (P = 0.068). In multivariate analysis, TLR9 expression was prognostically insignificant due to heavy correlation to disease stage and higher gradus. Treating UT-MUC-1 cells with TLR9 ligand CpG in vitro induced MMP-13 expression and invasion in Matrigel(®) invasion assay, whereas decreased invasion was seen in myoma organotypic model., Conclusion: Functional TLR9 is present in salivary MEC, and high level of expression may indicate good prognosis. However, more studies are needed to evaluate biological consequences of TLR9 interaction in tumor cells., (© 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Oral tongue squamous cell carcinoma (OTSCC) often metastasizes to cervical lymph nodes. Mechanisms of this disease progression are not fully known. We aimed at finding new predictive markers for diagnosis and disease monitoring., Methods: Seventy-three consecutive T1N0M0 and T2N0M0 OTSCC patients treated at Helsinki University Central Hospital, Helsinki, Finland, in 1992-2002 were included. Tissue array blocks were prepared from primary tumors and immunostained. Immunoexpression of matrix metalloproteinase (MMP)-2, -8, -9, and -13 was compared with patient characteristics and outcome., Results: Nuclear expression of MMP-13, but not cytoplasmic expression of MMP-2, -8, and -9, was associated with invasion depth (P = 0.017) and tumor size (P = 0.008). Furthermore, high nuclear MMP-13 expression was predictive of poor outcome (P = 0.042)., Conclusion: Our results suggest that especially MMP-13 may be regarded as a prognostic biomarker in OTSCC., (© 2011 John Wiley & Sons A/S.)

The purpose of this study was to identify plasminogen activators (PA) and their specific inhibitors in human cell-free saliva and to investigate their expression in salivary gland tissue. Saliva samples were obtained from 34 patients visiting a neurological out-patient department. The activities of tissue and urokinase plasminogen activators (tPA and uPA, respectively), the relative inhibition of tPA, and the amounts of plasminogen activator inhibitors 1 and 2 (PAI-1 and PAI-2, respectively) in cell-free saliva were studied. The activities of tPA and uPA, and tPA inhibition, were measured using in-house microtiter plate assays, and PAI-1 and PAI-2 levels were measured using commercial enzyme-linked immunosorbent assay (ELISA) kits. Immunohistochemistry was used to evaluate the expression of PAs and PAIs in the salivary gland. Tissue plasminogen activator activity was found in most samples, with a mean activity of 0.63 IU ml(-1). uPA was observed in only a few samples. PAI-1 was not detected, but PAI-2 was present in all samples (with a mean value of 11.1 ng ml(-1)). The mean PAI-2 level in women was 12.4 and in men was 7.6 ng ml(-1). The activity of tPA and the relative inhibition of tPA seemed to be inversely associated. Tissue plasminogen activator, PAI-1, and PAI-2 were evident in salivary gland tissue, whereas the expression of uPA was low. The tPA activity in saliva suggests an active proteolysis. Plasminogen activator inhibitor 2 was found to be the main inhibitor of PAs in saliva.

Objective: To evaluate the histology of minced and injected autologous fascia graft in the augmentation of unilateral vocal fold paralysis., Study Design: Prospective study using a canine model., Methods: Nine dogs were operated. At first, a piece of fascia was harvested from fascia lata and minced into tiny chips with a scalpel. Cutting off a section of the recurrent nerve paralyzed the right vocal fold. The minced fascia-paste (0.1 mL) was injected using a pressure syringe into the paralyzed thyroarytenoid muscle under direct laryngoscopy. Two animals were killed at 3 days, one at 10 days, three at 6 months, and three at 12 months postinjection. Each dog underwent laryngectomy and serial coronal sections of paraffin blocks from the posterior part of the vocal folds were made., Results: The dogs experienced no complications perioperatively or during follow-up. Under microscopy, muscle of the paralyzed vocal fold was atrophied in comparison to the contralateral control. There was an acute inflammatory reaction induced by the graft. This did not exist in the specimens taken at 6 and 12 months. No extensive edema, areas of necrosis, or formation of granulomas was seen at any time. Maturation of the graft was characterized by active collagen remodeling up to 12 months. At that time the graft consisted of firm, condensed fibrous tissue. Scar formation around the graft was moderate, and the subepithelial layer of the vocal fold remained undisturbed. Each graft consisted of singular foreign bodies from the polyamide mincing plate. We cannot exclude that their presence would have had an impact on the final architecture of the graft., Conclusion: In a canine vocal fold, the free fascia graft is well tolerated and after 12 months a well-organized, collagen rich tissue is seen on histological sections. The findings are in accordance with clinical studies applying free fascia grafts.