DNA Methylation of the ABO Promoter Underlies Loss of ABO Allelic Expression in a Significant Proportion of Leukemic Patients

Background: Loss of A, B and H antigens from the red blood cells of patients with myeloid malignancies is a frequent occurrence. Previously, we have reported alterations in ABH antigens on the red blood cells of 55% of patients with myeloid malignancies. Methodology/Principal Findings: To determine the underlying molecular mechanisms of this loss, we assessed ABO allelic expression in 21 patients with ABH antigen loss previously identified by flow cytometric analysis as well as an additional 7 patients detected with ABH antigen changes by serology. When assessing ABO mRNA allelic expression, 6/12 (50%) patients with ABH antigen loss detected by flow cytometry and 5/7 (71%) of the patients with ABH antigen loss detected by serology had a corresponding ABO mRNA allelic loss of expression. We examined the ABO locus for copy number and DNA methylation alterations in 21 patients, 11 with loss of expression of one or both ABO alleles, and 10 patients with no detectable allelic loss of ABO mRNA expression. No loss of heterozygosity (LOH) at the ABO locus was observed in these patients. However in 8/11 (73%) patients with loss of ABO allelic expression, the ABO promoter was methylated compared with 2/10 (20%) of patients with no ABO allelic expression loss (P = 0.03). Conclusions/Significance: We have found that loss of ABH antigens in patients with hematological malignancies is associated with a corresponding loss of ABO allelic expression in a significant proportion of patients. Loss of ABO allelic expression was strongly associated with DNA methylation of the ABO promoter.Tina Bianco-Miotto, Damian J. Hussey, Tanya K. Day, Denise S. O'Keefe and Alexander Dobrovi

Recent advances in immunohistochemistry in the diagnosis of ovarian neoplasms

This leader reviews recent advances in immunohistochemistry that are useful in the diagnosis of ovarian neoplasms. These include the value of different anticytokeratin antibodies in the distinction between a primary ovarian adenocarcinoma and a metastatic adenocarcinoma, especially of colorectal origin. These antibodies have also helped to clarify the origin of the peritoneal disease in most cases of pseudomyxoma peritonei. The value of antibodies against so called tumour specific antigens, such as CA125 and HAM56, in determining the ovarian origin of an adenocarcinoma is also reviewed. In recent years, several studies have investigated the value of a variety of monoclonal antibodies in the diagnosis of ovarian sex cord stromal tumours and in the distinction between these neoplasms and their histological mimics. These antibodies include those directed against inhibin, CD99, Mullerian inhibiting substance, relaxin like factor, melan A, and calretinin. Of these, anti-α inhibin appears to be of most diagnostic value. It is stressed that these antibodies should always be used as part of a larger panel and not in isolation.J Clin Pathol(J Clin Pathol 2000;53:327–334) Key Words: ovarian neoplasms • diagnosis • immunohistochemistr