Cytokeratin 7/20 and MUC1, 2, 5AC, and 6 expression patterns in Barrett's esophagus and intestinal metaplasia of the stomach: intestinal metaplasia of the cardia is related to Barrett's esophagus.

Intestinal metaplasia (IM) in endoscopic biopsies obtained from close to the gastroesophageal junction may represent IM of the cardia (CIM) or Barrett's esophagus (BE), which have different malignant potentials despite similar morphology. This study compared cytokeratin (CK) 7/20 and mucin (MUC1, 2, 5AC, and 6) immunopatterns in biopsies from BE (n = 41), CIM (n = 35), and antral gastric IM (AIM, n = 37) to evaluate their roles as diagnostic aids. CK7 and CK20 expression was described as absent, patchy (superficial and deep), continuous superficial only, continuous deep only, and diffuse. Eleven different combinations of CK7/20 expression were seen. Since CK20 staining was positive in all cases, four main patterns were defined on the basis of the observed CK7 staining as 1, absent; 2, patchy (superficial and/or deep); 3, diffuse; and 4, continuous superficial only. Overall CK7 positivity (regardless of pattern) was higher in BE and CIM than in AIM. CK patterns 3 and 4 were also higher in BE and CIM than in AIM. For either pattern 3 or 4, the positive and negative predictive values for BE versus AIM were 95% and 67%, respectively. MUC1 was rarely expressed in BE and CIM compared with AIM, whereas the opposite was noted for MUC5AC expression. MUC2 and MUC6 expression was similar in all locations. In conclusion, diffuse or continuous superficial CK7 staining is highly characteristic of BE and CIM and contrasts with AIM. It is, however, not very sensitive. CK20 profiles have no added value. Mucin expression also differs between BE and CIM versus AIM, but the specificity of any pattern is insufficient for distinction in individual cases. Importantly, CK and MUC expression patterns in BE and CIM are virtually indistinguishable, limiting their use in this differential and raising the question of whether they are biologically related.     

Leiomyosarcoma and malignant fibrous histiocytoma share similar allelic imbalance pattern at 9p

Formalin-fixed, paraffin-embedded tissue from 45 soft tissue sarcomas was analysed for allelic imbalance/loss of heterozygosity (AI/LOH) of chromosome 9. The specimens consisted of 17 cases of soft tissue leiomyosarcoma (LMS), 4 cases of cutaneous LMS, 22 cases of conventional malignant fibrous histiocytoma (MFH) and 2 cases of angiomatoid fibrous histiocytoma. All cases were categorised morphologically and immunohistochemically. DNA was microdissected from normal and neoplastic tissues. AI/LOH was performed using six microsatellite markers on the 9p region. The frequency of allelic imbalance at different loci on chromosome 9p was analysed in LMS and MFH and then compared with values previously examined in synovial sarcoma and malignant peripheral nerve sheath tumour. Although AI/LOH and microsatellite instability (MSI) were more frequent in MFH, LMS and MFH groups showed similar patterns of allelic imbalance at the 9p region. Alterations of chromosome 9p have been reported in many cell lines and tumours including LMS and MFH. 9p21 region encodes p16^INK4A and p15^INK4B. Allelic imbalance observed at 9p 21 in this study suggests that alterations of the negative cell cycle regulators may be an important step in the pathogenesis of MFH and LMS. However, the most frequent allelic imbalance was observed at 9p24 at D9S230. Alterations of this locus were very rare in synovial sarcoma and malignant peripheral nerve sheath tumours and were absent in cutaneous LMS and angiomatoid fibrous histiocytoma. This locus may point to the existence of a genetically altered tumour suppressor gene involved in the pathogenesis of LMS and MFH. Our results support the hypothesis that MFHs may represent a morphological pathway in tumour progression of LMSs.     

Paternal age and birth defects: how strong is the association?

BACKGROUND: Although the association between maternal age and the risks of birth defects has been well studied, the evidence from population data linking paternal age with birth defects was limited and inconsistent. METHODS: We conducted a population-based retrospective cohort study of 5,213,248 subjects from the 1999-2000 birth registration data of the USA. Multiple logistic regressions were used to estimate the independent effect of paternal age on all birth defects and 21 specific defects groups after adjusting for potential confounding of maternal age, race, education, marital status, parity, prenatal care initiation, maternal smoking and alcohol drinking during pregnancy. RESULTS: A total of 77,514 (1.5%) birth defects were recorded in the study cohort. The adjusted odds ratios were 1.04 (1.01, 1.06), 1.08 (1.04, 1.12), 1.08 (1.02, 1.14) and 1.15 (1.06, 1.24), respectively, for infants born to fathers 30-35, 40-44, 45-49 and over 50 years (test for trend, P = 0.0155), when compared with those infants born to fathers aged 25-29 for any birth defect. Advanced paternal age was associated with increased risks of heart defects, tracheo-oesophageal fistulaoesophageal atresia, other musculoskeletal/integumental anomalies, Down's syndrome and other chromosomal anomalies. Fathers under 25 years of age were also at increased risks of spina bifida/meningocele, microcephalus, omphalocele/gastroschisis and other musculoskeletal/integumental anomalies. CONCLUSIONS: Infants born to older fathers have a slightly increased risk of birth defects. Young paternal age is also associated with slightly increased risk of several selected birth defects in their offspring. However, given the weak association, paternal age appears to play a small role in the aetiology of birth defects.