Genotypic and phenotypic variability of 22q11.2 microduplications: An institutional experience

Duplications in the 22q11.2 region can cause 22q11.2 duplication syndrome and encompass a variety of phenotypes including developmental delays, facial abnormalities, cardiovascular defects, central nervous system delays, and other congenital abnormalities. However, the contribution of these contiguous duplicated regions to the clinical phenotypes has not been fully elucidated. In this study, we identified nine patients carrying different 22q11.2 microduplications detected by chromosomal microarray. Of these patients, seven pediatric patients presented with various clinical features including two neonate cases died shortly after birth, and two healthy adults. We examined region specific genotype–phenotype associations and found unpredictability associated with 22q11.2 duplications in these nine patients.     

The value of fine-needle aspiration biopsy in the cytodiagnosis of salivary gland lesions

Fine-needle aspiration cytology (FNAC) was performed on 195 cases of salivary gland lesions. The smears were technically adequate in 178 cases. Tissue examination was available for subsequent histocytologic correlation in 57 cases. The cytodiagnosis included inflammatory lesions (59) and benign (68) and malignant (51) tumors (total, 119). The accuracy of cytodiagnosis was 87.7% with a sensitivity of 80.9% and a specificity of 94.3%. Exact histologic typing was possible in 61.9% of the malignant tumors. Mucoepidermoid tumors and cellular-atypical pleomorphic adenoma posed difficulties in cytodiagnosis.     

The diagnostic usefulness of tumour markers CEA and CA-125 in pleural effusion

Pleural effusion is a common diagnostic problem. The analysis of serum and pleural fluid for tumour markers is widely used as a diagnostic aid in clinical practice. The aim of the present study was to determine the usefulness of simultaneous quantification of carcinoembryonic antigen (CEA) and carbohydrate antigen (CA-125) in distinction of malignant from benign effusion. Data from a total of 78 patients including 53 patients with benign and 25 patients with malignant effusion was evaluated. The cut-off values for differentiating benign from malignant effusions were determined using results obtained from patients with known benign effusions (mean + 2 SD, 95% confidence interval). The cut-off for CEA and CA-125 were 5.1 ng/ml and 1707 IU/ml respectively. CEA assay in pleural fluid had an acceptable sensitivity and good specificity of 64% and 98% respectively. CA-125 had a sensitivity of 36% and specificity of 94%. The combination of the two tumour markers gave a sensitivity of 72% and specificity of 92.4%. We suggest a good clinical strategy may be to begin with CEA measurement (assay specificity 98%); if CEA is below the cut-off value (negative), CA-125 could then be measured to improve the sensitivity of detection of malignant effusions. However, measurement of these tumour markers is not cost effective from the point of view that it does not give information on the type of malignancy present. The latter has to be determined either by histological or cytological study.     

Cytokeratin 5/6 in normal human breast: lack of evidence for a stem cell phenotype

In recent studies, B?cker and colleagues described a population of cells in paraffin wax sections of normal human breast that express cytokeratins (CK) 5/6 without expression of CK8/18 or smooth muscle actin (SMA). They proposed that these represent stem cells that give rise to differentiated luminal and myoepithelial cells. The data have been used to generate a model for breast cancer progression and classification with associated implications for management of pre-invasive disease. In this study, the expression of CK5/6, CK8/18, and SMA was investigated using multiple immunofluorescence on matched pairs of paraffin wax-embedded and frozen breast specimens. The staining patterns reported previously in antigen-retrieved paraffin wax-embedded sections were confirmed but no CK5/6-only cells were found in frozen sections of normal breast. There were cells with low levels of CK8/18 expression in frozen sections that may correspond to the CK8/18 'negative' cells seen in paraffin wax sections. This study brings into question the previously described profile of breast 'stem cells' based on CK5/6 staining and hence the breast cancer progression model and classification based on this phenotype.     

Acidic ATP activates lymphocyte outwardly rectifying chloride channels via a novel pathway

Using whole-cell patch-clamp techniques we found that ATP activated an outwardly rectifying current in Daudi human B lymphoma cells under acidic conditions. The substitution of Cl^– for gluconate^– shifted the reversal potential, while Cl^– channel blockers, 4,4-diisothiocyanostibene-2,2-disulfonic acid (DIDS) and 9-anthracene carboxylic acid (9-AC), blocked the current, indicating that ATP induces this current by activating the outwardly rectifying chloride channel (ORCC). The effect of ATP on ORCC was mimicked by ADP, but not by other P2 receptor agonists such as ATPS (a poorly hydrolyzable analog of ATP), 2,3-O-benzoyl-4-benzoyl-ATP (BzATP), and UTP. The ATP-induced ORCC current was completely blocked by 100 M suramin (a P2 receptor antagonist), and was partially blocked by 100 M pyridoxal-phosphate-6-azophenyl-2,4-disulfonic acid tetrasodium (PPADS), which is another P2 receptor antagonist. Neither inactivation of G proteins nor elimination of extracellular Ca²⁺ affected the ATP-induced current, indicating that G protein-coupled P2Y receptors and Ca²⁺-permeable P2X receptors are not involved. Based on the pharmacological profile and the fact that acidic conditions are required for ATP to activate the ORCC, we suggest that acidic ATP activates the lymphocyte ORCC via a novel pathway, which is not associated with any previously described purinergic receptors.     

Cytology of mucinous carcinoma of breast: a report of 28 cases with histological correlation

Pure mucinous carcinoma (MC) of the breast is a relatively uncommon variant of breast carcinoma with distinctive histological and cytological features. In this study we have analysed fine needle aspiration (FNA) cytological material from 28 cases of MC of breast and correlated the cytomorphological features with histopathology. The 28 patients consisted of 27 females and one male patient. 14 patients were Chinese, 10 were Indian and four were Malay. Their ages ranged from 38 to 90 with a mean at 52 years. The left breast was involved in 17 and the right in 11 cases. The duration of the lump varied from two weeks to 10 years. The cytological picture was characterized by abundant extracellular mucin giving a "sea of mucin" or "whirlpools of mucin" effect, in which were seen floating clusters of tumour cells with relatively bland cytological features. Myxo-vascular fragments were seen in 12 cases. Dissociated tumour cells showed a plasmacytoid appearance with eccentric nuclei. In four cases, the mucin was scanty in amount and the cellularity was high while in two cases, the cellularity was very low. Psammoma bodies were seen in cytological smears in one case. Histological study of excision or mastectomy specimens confirmed all 28 cases to be pure MC. Knowledge of the distinctive cytomorphological appearance of MC would enable correct identification of these lesions as malignant and prompt treatment that could further enhance the survival of these prognostically good breast cancers.     

Total hemolytic complement (CH50) and its fractions (C3 and C4) in the sera of patients with carcinoma of the oral cavity,uterine cervix,and breast

The total hemolytic complement activity of CH50 and its fractions C3 and C4 was determined in the sera of 196 patients with carcinoma of the oral cavity, 172 patients with carcinoma of the uterine cervix, and 166 patients with breast cancer. The values were compared with those of 18 patients with mammary dysplasia, 32 patients with mild to moderate dysplasia of the cervix, and 100 healthy, normal age- and sex-matched controls. No alterations in CH50, C3, and C4 were observed in the sera of patients with benign lesions, whereas a significant rise in the three factors was observed in all the cancer patients studied. The complement activity increased significantly with the progression of the disease up to stage III and remained persistently elevated thereafter. Patients who had a clinical cure had normal levels of CH50, C3, and C4, whereas the values remained elevated in patients who were still undergoing treatment for residual lesions.