Genetic imbalances detected by multiplex ligation-dependent probe amplification in a cohort of patients with oral squamous cell carcinoma—the first step towards clinical personalized medicine

Oral tumors are a growing health problem worldwide; thus, it is mandatory to establish genetic markers in order to improve diagnosis and early detection of tumors, control relapses and, ultimately, delineate individualized therapies. This study was the first to evaluate and discuss the clinical applicability of a multiplex ligation-dependent probe amplification (MLPA) probe panel directed to head and neck cancer. Thirty primary oral squamous cell tumors were analyzed using the P428 MLPA probe panel. We detected genetic imbalances in 26 patients and observed a consistent pattern of distribution of genetic alterations in terms of losses and gains for some chromosomes, particularly for chromosomes 3, 8, and 11. Regarding the latter, some specific genes were highlighted due to frequent losses of genetic material—RARB, FHIT, CSMD1, GATA4, and MTUS1—and others due to gains—MCCC1, MYC, WISP1, PTK2, CCND1, FGF4, FADD, and CTTN. We also verified that the gains of MYC and WISP1 genes seem to suggest higher propensity of tumors localized in the floor of the mouth. This study proved the value of this MLPA probe panel for a first-tier analysis of oral tumors. The probemix was developed to include target regions that have been already shown to be of diagnostic/prognostic relevance for oral tumors. Furthermore, this study emphasized several of those specific genetic targets, suggesting its importance to oral tumor development, to predict patients’ outcomes, and also to guide the development of novel molecular therapies.     

Immunohistochemical assessment of CD1a‐positive Langerhans cells and their relationship with E‐cadherin in minor salivary gland tumors

J Oral Pathol Med (2012) 41 : 47–53 Objective: The aim of this study was to investigate the presence of CD1a‐positive Langerhans cells and their relationship with E‐cadherin in minor salivary gland tumors. Methods: Twenty‐seven minor salivary gland tumors were investigated using immunohistochemistry for CD1a and E‐cadherin. Results: A significant difference regarding the mean density of CD1a‐positive Langerhans cells was observed between pleomorphic adenomas and malignant tumors studied (P = 0.001). No CD1a‐positive cells were detected in most cases (n = 5) of cystic adenoid carcinomas. CD1a‐positive cells were detected in one mucoepidermoid carcinoma case, and six low‐grade polymorphous adenocarcinomas cases. Comparison of the mean density of CD1a‐positive cells between the three malignant tumors showed no significant difference (P = 0.127). No significant difference was observed in the presence of E‐cadherin between tumors (P = 0.73), but it was detected in 24 cases. Conclusions: The lack of CD1a‐positive in malignant salivary gland tumors facilitates the neoplastic development and suggests that these cells might be useful as auxiliary diagnostic and prognostic tool in minor salivary gland tumors. Furthermore, it is suggested that E‐cadherin mediates cell adhesion in these tumors although we did not demonstrate significance.     

Inclusion of supine period in short-duration pH monitoring is essential in diagnosis of gastroesophageal reflux disease

Prolonged esophageal pH monitoring is the most accurate method for detecting abnormal gastroesophageal reflux (GER) in patients with gastroesophageal reflux disease (GERD). However, some investigators have found that short-duration postprandial pH monitoring in the upright position is also useful, while others have failed to find such results. Therefore, we have compared a 6-hr period of pH monitoring (3-hr postprandial period after daytime meal and 3-hr supine period) with a total 24-hr period in detecting abnormal gastroesophageal reflux. Sixty-five patients (44 men, mean age 41.3 years) with GERD and 16 healthy volunteers (11 men, mean age 34.3 years) underwent 24-hr pH monitoring according to a standard protocol. Various reflux parameters during 24-hr pH monitoring were compared with reflux parameters during the 6-hr period. Abnormal GER was detected in 56 patients presenting with typical symptoms of GERD (sensitivity 86.2%). These patients could be further divided into upright (N=18), supine (N=15), and combined (N=23) refluxers, depending on the posture in which abnormal reflux occurred. Esophageal pH monitoring during the 3-hr postprandial upright period showed abnormal reflux in only 35 patients (sensitivity 53.8%;P<0.00005, compared with the 24-hr pH monitoring period). Abnormal GER was identified in 13 of 18 upright, 19 of 23 combined, and only one of 15 supine refluxers, as well as in two of nine patients with normal 24-hr pH-metry. However, inclusion of the 3-hr supine monitoring period in the 3-hr postprandial upright period improved detection of abnormal GER to 78.5% (51 patients;P=NS compared with 24-hr pH monitoring period). This was related mainly to improved detection of abnormal GER in supine refluxers (11 of 15; 73.3%). Esophageal acid exposure time correlated significantly with severity of esophagitis only during the total and supine periods of both the 24- and 6-hr periods and not during the upright period. Esophageal acid clearance correlated significantly with increasing grades of esophagitis for the supine and total periods only. We conclude that 3-hr postprandial pH monitoring, as has been conventionally practiced, is not appropriate in the detection of abnormal GER; inclusion of a supine period in the short-duration pH monitoring schedule increases the detection of pathological reflux. We therefore recommend that a supine period should be included in short-duration pH monitoring schedules. We also found that supine reflux was the most important factor in the development of esophagitis.     

Two cases of Kallmann syndrome associated with empty sella

Kallmann syndrome (KS) is a developmental disease characterized by the association of isolated hypogonadotropic hypogonadism and anosmia/hyposmia. We report an unusual presentation of two females with KS and empty sella. These females, aged at 20 and 29-year-old, presented primary amenorrhea with prepubertal estradiol and low gonadotropin levels. No other significant clinical signs were observed. Empty sella was observed on MRI in both cases. Sequencing of FGFR1 gene, recently implicated in autosomal form of KS, was performed and one splicing mutation (IVS14 + 1G > A) was identified in one patient.     

Sleep disordered breathing – a new component of syndrome x?

Sleep disordered breathing (SDB) is a complication of obesity estimated to occur in about 4–6% of overweight individuals. These respiratory disturbances during sleep incorporate a number of conditions including snoring, upper airway resistance syndrome and obstructive sleep apnoea syndrome (OSAS). It is thought that as well as having deleterious effects on sleep quality these conditions may also promote cardiovascular and hormonal changes leading to an elevated blood pressure and an increased incidence of cardiovascular morbidity. Evidence reviewed here points to an alteration in sympathovagal balance, baroreceptor sensitivity, insulin resistance and leptin, growth hormone and lipid levels. Whether these changes are a consequence of the associated obesity or the SDB itself remains to be proven.     

Role of bacterial toxins,bile acids,and free fatty acids in colonic water malabsorption in tropical sprue

Colonic perfusion studies in 10 southern Indian patients with tropical sprue and nine matched healthy adults revealed a defect of water and sodium absorption from the colon in sprue. Heat-labile and heat-stable enterotoxin production was not detected in coliforms cultured from the feces of any of the 19 subjects. The 24-hr fecal bile acid output was increased in patients with sprue, but fecal aqueous bile acid concentrations remained within normal limits, and these did not correlate with defects in colonic water and sodium absorption. Fecal free fatty acid excretion was markedly increased in sprue. There was a negative correlation between fecal excretion of unsaturated free fatty acids and colonic water and sodium absorption.