The Relationship between the Methylenetetrahydrofolate Reductase Genotypes and the Methylation Status of the CpG Island Loci, LINE-1 and Alu in Prostate Adenocarcinoma

BACKGROUND: Genetic polymorphism of methylenetetrahydrofolate reductase (MTHFR), in association with the influence of MTHFR upon DNA methylation, may cause differences of the methylation profile of cancer. Thus, we investigated the relationship between the methylation status of prostate adenocarcinoma and the genetic polymorphism of MTHFR. METHODS: We examined 179 cases of prostate adenocarcinoma for determining the genotypes of MTHFR 677 and 1298, the methylation status of 16 CpG island loci and the methylation levels of the LINE-1 and Alu repeats with using polymerase chain reaction/restriction fragment length polymorphism, methylation-specific polymerase chain reaction and combined bisulphite restriction analysis, respectively. RESULTS: There was a higher proportion of the CT genotype of MTHFR 677 in the prostate adenocarcinoma than that in the normal control. The TT genotype of MTHFR 677 showed the highest frequency of methylation in six out of nine major CpG island loci, and these were which were frequently hypermethylated in prostate adenocarcinoma. The CT type showed the lowest methylation levels of LINE-1 and Alu among the MTHFR 677 genotypes. Interestingly, the CC type of MTHFR 1298 demonstrated favorable prognostic factors. CONCLUSIONS: Our study is the first to examine the methylation profile of prostate adenocarcinoma according to the MTHFR genotypes. The differences of the cancer risk, the genomic hypomethylation and the prognosis between the MTHFR genotypes in prostate adenocarcinoma should be further explored.

The Prognostic Significance of Neuroendocrine Differentiation for Treating Prostatic Carcinoma in 699 Cases of Radical Prostatectomy

BACKGROUND: Neuroendocrine differentiation of prostatic carcinoma is known to be associated with a poor prognosis, tumor progression and androgen-independency, and there is currently no successful therapy for this type of tumor. The purpose of this study is to evaluate the prognostic implications of neuroendocrine differentiation in prostatic carcinoma in Korean men. METHODS: Six hundreds and ninety nine consecutive cases of radical prostatectomy specimens were systematically processed for topographic mapping. Neuroendocrine differentiation was detected by immunohistochemistry by using antibody to chromogranin. We analyzed the relationship between neuroendocrine differentiation and the clinicopathological prognostic factors, as well as biochemical failure. The neuroendocrine differentiation was evaluated according to the presence of chromogranin-positive cells, the pattern of neuroendocrine cells and the number of neuroendocrine cells, respectively. RESULTS: Neuroendocrine differentiation was detected in 150 out of 699 cases (21.5%). The presence of neuroendocrine differentiation as well as the pattern of neuroendocrine cells was correlated with biochemical failure and the other clinicopathological prognostic factors such as the Gleason score, the pathologic stage, the tumor volume, angiolymphatic invasion, perineural invasion, and the Ki-67 proliferative index (p<0.05). CONCLUSIONS: We suggest that neuroendocrine differentiation of prostatic carcinoma is a prognostic factor even in radical prostatectomy specimens for localized prostate cancer. Evaluation of the presence of neuroendocrine differentiation as well as the pattern of neuroendocrine cells is recommended in radical prostatectomy specimens.

Methylation Profiles of CpG Island Loci in Major Types of Human Cancers

Several reports have described aberrant methylation in various types of human cancers. However, the interpretation of methylation frequency in various human cancers has some limitations because of the different materials and methods used for methylation analysis. To gain an insight into the role of DNA hypermethylation in human cancers and allow direct comparison of tissue specific methylation, we generated methylation profiles in 328 human cancers, including 24 breast, 48 colon, 61 stomach, 48 liver, 37 larynx, 24 lung, 40 prostate, and 46 uterine cervical cancer samples by analyzing CpG island hypermethylation of 13 genes using methylation-specific PCR. The mean numbers of methylated genes were 6.5, 4.4, 3.6, 3.4, 3.1, 3.1, 3.1, and 2.1 in gastric, liver, prostate, larynx, colon, lung, uterine cervix, and in breast cancer samples, respectively. The number of genes that were methylated at a frequency of more than 40% in each tumor type ranged from nine (stomach) to one (breast). Generally genes frequently methylated in a specific cancer type differed from those methylated in other cancer types. The findings indicate that aberrant CpG island hypermethylation is a frequent finding in human cancers of various tissue types, and each tissue type has its own distinct methylation pattern.

Acinar Cell Cystadenoma of the Pancreas: Report of a Case with Metaplastic Ossification

Acinar cell cystadenoma (ACA) is a very rare cystic lesion of the pancreas. The lining epithelium of ACA is morphologically identical to acinar cells of the pancreas. It is uncertain whether ACA is a benign neoplasm or cystic transformation of acinar glands but it is worthy to consider ACA in the differential diagnosis of other cystic neoplasms of the pancreas. We report here a 25-year old-woman who was operated on for a cystic mass of the pancreas. Grossly, a multilocular cystic mass containing clear serous fluid was observed. There was no communication between the cysts and the pancreatic ducts. Microscopically, cysts of various size were lined by columnar, cuboidal or flattened epithelial cells with a few foci of pseudostratification. The cells had granular apical cytoplasm and basally located nuclei with minimal atypia, the same as normal acinar cells. Metaplastic ossification was noted in the stroma. Immunohistochemically, the lining epithelium was positive for cytokeratin 7, antitrypsin and antichymotrypsin.