Methylation of an intronic region regulates miR-199a in testicular tumor malignancy.

In the testicular cancer cell line, NT2, we previously demonstrated that differentially methylated regions were located in introns or intergenic regions, and postulated these might regulate non-coding RNAs. Three microRNAs and three small nucleolar RNAs were differentially methylated; one, miR-199a, was associated with the progression and prognosis of gastric and ovarian cancers. In this report we document, by epigenomic profiling of testicular tissue, that miR-199a is transcribed as antisense of dynamin 3 (chromosome 1q24.3), and hypermethylation of this region is correlated with miR-199a-5p/3p repression and tumor malignancy. Re-expression of miR-199a in testicular cancer cells led to suppression of cell growth, cancer migration, invasion and metastasis. The miR-199a-5p, one of two mature miRNA species derived from miR-199a, is associated with tumor malignancy. We further identified the embryonal carcinoma antigen podocalyxin-like protein 1 (PODXL), an anti-adhesive protein expressed in aggressive tumors, as a target of miR-199a-5p. We demonstrated PODXL is overexpressed in malignant testicular tumor, and cellular depletion of PODXL resulted in suppression of cancer invasion. The inverse relationship between PODXL and miR-199a-5p expression suggests PODXL is a downstream effector mediating the action of miR199a-5p. This report identifies DNA methylation, miR-199a dysregulation and PODXL as critical factors in tumor malignancy.

Calcification in breast lesions: pathologists' perspective.

Evaluation of calcification in breast lesions is a major assessment criterion for breast mammography. The morphology and distribution of the calcification are related to the histology of the lesions. Radiologically, calcifications can be divided into: benign; intermediate concern; and higher probability of malignancy according to the morphology. Different pathological entities may give rise to different calcifications. Fibrocystic changes may give rise to milk of calcium or teacup type calcification, or small calcifications occurring in a cluster. Fibroadenoma may be associated with large popcorn like calcifications, and sclerosing adenosis may have fine, punctate or granular calcifications. Fat necrosis may give rise to egg shell calcification. Precursor malignant lesions give rise to benign to indeterminate type calcifications, and may occasionally be associated with malignant type calcifications. For malignant lesions, ductal carcinoma in situ and invasive duct carcinoma may be associated with large irregular, rod or V shaped, pleomorphic or branching type calcifications that follow the distribution of the duct. Furthermore, analysis of the characteristics of the calcifications may help to predict the tumour size and grade, and presence of invasion.

Computer-assisted detection as a second reader in symptomatic Asian women with palpable breast cancer.

PURPOSE: To determine the potential role of a computer-assisted detection (CAD) algorithm as a second reader for experienced and inexperienced radiologists in mammography reading in Asian women. MATERIAL AND METHODS: Two-view mammograms performed in 124 consecutive patients who presented with palpable breast cancer masses were retrospectively evaluated by two experienced breast radiologists (7 and 10 years' experience). The original reports of the session radiologists with variable experience of reading mammograms (2 to more than 10 years) were also evaluated. The number of suspicious masses and microcalcification clusters detected in each patient by both groups of radiologists were recorded. The radiologists then re-evaluated the films with the CAD system as a second reader. Any improvement in the detectability of breast pathology by either the experienced radiologists and/or by the session radiologists was then assessed. A total of 127 breasts had biopsy-proven carcinoma; 74 breasts had mastectomy performed. All the imaging results were correlated with tru-cut biopsy or mastectomy histology. RESULTS: With CAD-aided interpretation, there were altogether 95 visible masses and 77 suspicious microcalcification clusters in 109 mammographically detectable cancers correlated with histology results. There was a 7.4% (7/95) and 10.4% (8/77) increase in the number of masses and microcalcification clusters detected, respectively, by the experienced radiologists after application of CAD, whereas the increase was 13.7% (13/95) and 27.3% (21/77) for detection of masses and microcalcifications by the session radiologists, respectively. In 9 patients, a secondary focus detected by CAD was confirmed by histology. Three patients had contralateral breast tumors, 1 had a satellite invasive tumor while 5 had ductal carcinoma in situ on the same breast. Based on the biopsies and 74 mastectomies, the true-positive and false-positive detection rate of CAD was 92.6% and 31.8% for detection of carcinomas. The true-positive and false-positive detection rates were 100% and 58.8% for microcalcification clusters. CONCLUSION: The current generation CAD algorithm helped to improve the detection rate of carcinomas, calcifications and multifocality in Asian breasts.