HPV infection in oropharyngeal squamous cell carcinomas: correlation with tumor size.

PURPOSE: Human papillomavirus (HPV) is implicated in carcinogenesis of a variety of epithelia, including oropharyngeal and laryngeal. High risk (HR) HPV persistent infection in head and neck squamous cell carcinomas (HNSCC) is a significant event, but its influence regarding the prognosis and survival in these patients remains under consideration. Our aim was to analyze a series of oropharyngeal (OP) SCCs at the HPV DNA level, correlating them to the survival status of the corresponding patients. METHODS: Using HPV DNA polymerase chain reaction (PCR) microarray technology, 28 formalin-fixed, paraffinembedded primary OPSCCs were cored and analyzed. RESULTS: Positive DNA amplicons for HPV infection were detected in 3 SCC cases (sub types: HPV 31/35/70). Interestingly, HPV persistent infection was associated with larger tumors (p=0.029) which also affected survival status (p=0.007) in the corresponding patients. Overall survival was also significantly dependent on the stage of the malignancies (p=0.022). Furthermore, tumor size was significantly and negatively correlated with age (p=0.015), meaning that younger patients will probably develop larger tumors. CONCLUSIONS: HPV-depended OPSCCs - although not so common as the laryngeal ones, but still not so rare in the rural population in Greece - are characterized by a combination of specific features. Our results showed that survival was adversely effected by the stage of the disease and tumor size and indirectly by the presence of HPV - especially in young adults - while the combined surgery/radiotherapy/ chemotherapy therapy seems to prolong survival. Additionally, HPV co-existence seems to be associated with larger tumors and poor survival.

Deregulation of PTEN Expression in Laryngeal Squamous Cell Carcinoma Based on Tissue Microarray Digital Analysis.

BACKGROUND/AIM: Phosphatase and tensin homolog (PTEN) (gene locus: 10q23.3) -a tumor suppressor gene- is deleted, mutated or epigenetically hyper-methylated in a variety of malignancies. PTEN acts as a negative regulator in PI3K/AKT/mTOR signaling transduction pathway. Our aim was to investigate PTEN protein expression patterns in laryngeal squamous cell carcinomas (LSCC). MATERIALS AND METHODS: Using tissue microarray technology, fifty (n=50) primary LSCCs were cored and re-embedded into one recipient block. Immunohistochemistry and digital image analysis were implemented for evaluating protein expression levels. RESULTS: Abnormal protein expression (low to negative staining intensity values) was observed in 28/50 (56%) tissue cores. Overall PTEN expression was associated with the anatomical region of the malignancies (p=0.039), whereas a borderline correlation with the differentiation grade was also assessed (p=0.05). CONCLUSION: Aberrant expression of PTEN tumor-suppressor gene in LSCCs seems to affect their biological behavior. Well-differentiated tumors express moderate to high protein levels, an evidence of normal gene function, whereas loss of its expression correlates with a progressive tumor dedifferentiation. Additionally, loss of its expression is detected more frequently in specific anatomical regions of the larynx (glottis, predominantly, and partially supraglottis).

mTOR deregulation in oral cavity squamous cell carcinoma.

Signal transduction pathways consist of a variety of inter- and intra-cellular molecules. They act as supporting mechanisms for cell survival and homeostasis. Among them, the phosphatidylinositol 3-kinase (PI3K)/tumor suppressor phosphatase and tensin homologue deleted on chromosome ten (PTEN)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) pathway plays a crucial role in regulating normal cell growth based on growth factor receptors (GFRs) interaction, including epidermal GFR (type II-HER2) and insulin GFR (IGF). mTOR protein acts as a serine-threonine kinase that belongs to the PI3K-related kinase family. It mediates protein and lipid synthesis, mitochondrial metabolism, biogenesis, proliferation and also negatively regulates autophagy. Two distinct multiprotein complexes have been mainly identified and cloned: mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2). mTOR is deregulated predominantly due to mutations, deletions, loss of heterozygosity (LOH) or abnormal phosphorylation of the upstream molecules inside the current pathway. Pure mTOR mutations are very rare. Development of specific inhibitors at the basis of targeted therapeutic strategies such as rapamycin (rapalogs) is an evolution in handling patients with mTOR abnormal overactivity. In the current special article we explored the role of the gene deregulation leading to abnormal protein expression in oral cavity squamous cell carcinoma (SCC).

Topoisomerase I deregulation in laryngeal squamous cell carcinomas based on tissue microarray analysis.

PURPOSE: Topoisomerases (types: I/IIa-b/IIIa-b) represent a super-family of nucleic enzymes involved in the DNA replication, transcription, recombination, and also chromosome topological formation. Topoisomerase's I (Topo I- gene location: 20q12) aberrant expression is a frequent genetic event in a variety of solid malignancies. Topo I inhibition promotes cell death due to DNA damage and for this reason it is a target for specific targeted chemotherapy (camptothecin, topotecan, irinotecan). Our aim was to investigate the role of abnormal Topo I protein expression in laryngeal squamous cell carcinomas (LSCC) in which there are very limited data regarding the influence of the marker. METHODS: Using tissue microarray (TMA) technology, 50 formalin-fixed, paraffin-embedded primary laryngeal SCCs were cored and re-pembedded into one recipient block. Immunohistochemistry was performed using anti- Topo I antibody. Digital image analysis was also implemented for evaluating objectively the protein expression levels on the corresponding stained nuclei. RESULTS: Topo I protein overexpression (moderate to high staining intensity values) was observed in 32/50 (64%) tissue cores, whereas low expression rates were detected in 18/50 (36%) cases. Topo I overall expression was strongly associated with the differentiation grade of the examined tumors (p=0.021). No other statistical correlations were identified. CONCLUSIONS: Topo I overexpression is observed in a significant subset of LSCCs affecting the level of differentiation in them. Additional molecular studies focused on the mechanism of Topo I gene/protein deregulation (i.e. amplification, abnormal epigenetic promoter methylation, mRNA aberrant expression) are necessary discriminating the eligible patients for applying specific chemotherapeutic strategies based on anti-Topo I agents.

Horner's Syndrome Incidental to Medullary Thyroid Carcinoma Excision: Case Report and Brief Literature Review.

Horner's syndrome is characterized by a combination of ipsilateral miosis, blepharoptosis, enophthalmos, facial anhidrosis, and iris heterochromia in existence of congenital lesions. The syndrome results from a disruption of the ipsilateral sympathetic innervation of the eye and ocular adnexa at different levels. Though rare, thyroid and neck surgery could be considered as possible causes of this clinical entity. We present a case of Horner's syndrome in a patient after total thyroidectomy and neck dissection for medullary thyroid cancer with neck nodal disease and attempt a brief review of the relevant literature.

Chronic rhinocerebral mucormycosis: a rare case report and review of the literature.

Rhinocerebral mucormycosis is an invasive infection caused by filamentous fungi of the Mucoraceae family. The rhinocerebral form of the disease represents the most common form and has two distinct clinical entities. The common presentation consists of a rapidly progressive infection with high mortality rate, while the other presentation is that of a chronic infection with lower mortality. In the present paper we report a rare case of chronic rhinocerebral mucormycosis. An 85-year-old male with a 6-month history of purulent and odorous nasal discharge, and sporadic episodes of epistaxis and anosmia, presented to the outpatient department of our clinic. Initial cultures were positive only for Pseudomonas aeruginosa. The patient was unresponsive to ciprofloxacin treatment, developing necrotic areas of the nasal septum suspicious for rhinocerebral mucormycosis. Admission to the ENT clinic followed, with histopathologic evaluation of the vomer bone confirming the diagnosis. The patient was treated with amphotericin B and was discharged 3 weeks later on oral posaconazole therapy. Chronic rhinocerebral mucormycosis may present with atypical symptoms or coinfection with another agent. A high degree of clinical suspicion is required for correct diagnosis and prompt initiation of appropriate treatment.

MMP-2 expression in 102 patients with glottic laryngeal cancer.

In order to evaluate the potential of matrix metalloproteinase 2 (MMP-2) as a prognostic factor for glottic laryngeal cancer. One hundred and two surgical specimens from patients with glottic laryngeal cancer who underwent laryngectomy for their disease in the University Hospital of Patras, Greece from 1998 to 2005 were reviewed retrospectively regarding MMP-2 expression via immunohistochemistry. Immunostaining was performed using a streptavidin-biotin peroxidase complex technique (LSAB). Results revealed that 54 of 102 patients (52.9%) had positive cytoplasmic staining for MMP-2. Kaplan-Meier analysis demonstrated statistically significant difference (p = 0.037) for the 5-year overall survival rate between the groups with positive and negative MMP-2 expression, and marginal statistical significance for the disease free survival rate (p = 0.048). The capsule rupture of metastatic lymph nodes and MMP-2 expression in primary tumor site also seems to be related (p = 0.047). Statistical significance could not be established between MMP-2 expression and the clinicopathological features of the disease (T stage, N stage, clinical stage, differentiation). In conclusion, MMP-2 expression was related with worse overall and disease-free survival and could be considered as a potential marker of poor prognosis.

Pharyngocutaneous fistula complicating laryngectomy: can metronidazole help?

AIM: To evaluate the use of metronidazole as a prophylactic agent against pharyngocutaneous fistula (PCF) formation. PATIENTS AND METHODS: Seventy patients who underwent total laryngectomy between 2000 and 2008 in our department were divided into two groups. The first group (M+ group) was placed on a 10-day metronidazole regimen (2 days prior to surgery and 7 days following). The second group (M- group) received only regular preoperative chemoprophylaxis. RESULTS: In total, 17 (24.3%) incidents of PCF were reported, 3 of which were in the M+ group, with the remainder in the M- group. A statistically significant reduction in the PCF rate was noted in favor of metronidazole in the overall population (p = 0.005), as well as in the patient group that had received radiotherapy prior to surgery (p = 0.03). CONCLUSION: Metronidazole administered for a total of 10 days pre- and postoperatively seems to lower the incidence rate of PCF formation.

Laryngeal cancer and passive smoking: the neglected factor?

In the present paper we investigate the relationship of environmental tobacco smoke (ETS) exposure to laryngeal cancer. 209 patients who were diagnosed with laryngeal cancer from 2000 to 2009 at the University Hospital of Patras, Western Greece, were reviewed with regard to patient age, disease stage at presentation, tumor differentiation, tobacco product use, alcohol consumption, occupation, and ETS exposure in the working environment. Pearson Chi-square method was used to determine the effect of ETS exposure on cancer stage, TNM classification and tumor differentiation in the dichotomized population (exposed vs. not exposed) and in groups of low, medium and high ETS exposure. ETS exposure in the working environment was found to significantly affect overall disease stage and T stage (p < 0.01) both in the dichotomic analysis and the group analysis. Minor significance was also noted for N stage (p = 0.047) in the exposure group analysis. Our data suggest that occupational ETS exposure presents a contributing risk factor for laryngeal cancer that requires further research to determine its significance.

Survival after laryngectomy: a review of 133 patients with laryngeal carcinoma.

Survival trends in survival for laryngeal cancer in Europe are varied. Five-year survival varied around 60-64% but numbers below 50% have been commonly reported. The aim of this study was to assess the factors influencing survival in patients with laryngeal cancer in our region. A total of 128 male and 5 female patients with larynx cancer (91 glottic and 42 supraglottic) were treated at Patras University Hospital between March 1992 and August 2004. Except 3, all were smokers and 56 (41%) heavy alcohol users. Postsurgical staging showed that most had been classified at stages III (38%) and IV (49%). By histology, 31 tumors were classified as poorly differentiated, 78 as moderately differentiated and 23 as well differentiated. All patients underwent laryngectomy with extension of the procedure where appropriate. Also, a total of 45 patients received adjuvant therapy (either chemotherapy or radiotherapy). Farmers, construction workers, professional drivers and mechanics and coffee shop and bar employees account for more than 70% of patients. Results showed that 64 (48.1%) patients died during the follow-up, 58 (43.6%) of them died from cause related to their disease. With a median follow-up of 25 months, the 5-year disease-free survival (DFS) was 53% and the 5-year overall survival (OS) was 45%. Significant prognostic factors for OS included patient age, advanced staging, heavy alcohol use and poor tumor differentiation while for DFS affected mainly by poor tumor differentiation. We conclude that the disease stage at presentation, tumor grade and alcohol consumption prove to be important predictors for the OS as well as the DFS in our series.

Tuberculosis of the parotid gland.

Tuberculosis (Tbc) presented as an isolated parotid mass is rare. Preoperative diagnosis is difficult and the symptomatology is nonspecific. In the majority of the cases an initial diagnosis of a parotid tumor, often a pleomorphic adenoma, is made. We present a 35-year old woman with a six months duration right parotid lump. The mass was firm and nontender without ipsilateral cervical lymphadenopathy, suggesting a parotid neoplasm. The computerized tomography scan showed an intraparotideal tumor resembling a pleomorphic adenoma and thus the patient underwent to a superficial parotidectomy. Fine needle aspiration biopsy was performed but it was not diagnostic. Histological examination revealed an intraparotideal lymph node with changes of granulomatous lymphadenopathy type, like those demonstrated in the tuberculosis and sarcoidosis. Ziehl-Nielsen staining was negative, while the tuberculin skin test (PPD, 5 IU) was positive. The patient's treatment regimen consisted of a 2-month initial phase of isoniazid, rifampin, pyrazinamide and ethambutol followed by a 7 month continuation phase of isoniazid and rifampin. Postoperatively, there was only a mild paresis of the facial nerve resolved a week after. Parotid Tbc is very rare but should be considered as a differential diagnosis of parotid lumps. Fine needle aspiration biopsy (FNAB) is of outmost importance for diagnosis, since the treatment of this entity is primarily conservative. However, surgery could be both therapeutic and diagnostic, especially when other diagnostic examinations fail.