Methylation Status of CpG Island of p16 in Benign, Atypical and Malignant Meningiomas

OBJECTIVE: Hypermethylation of p16, a tumor suppressor gene, has been frequently detected in a variety of cancer cells and is known to represent the level of p16 transcription. In human meningiomas, genetic alterations of p16 have shown to be infrequent. The purpose of this study is to investigate the role of p16 associated with the progression of meningiomas. METHODS: Sixty-eight meningiomas(randomly sampled 29 benign, 16 atypical and 23 malignant formalin-fixed, paraffin-embedded tissues) were analyzed. We examined the molecular mechanism of inactivation of p16 in these benign, atypical and malignant meningiomas by detecting the methylation status of p16 using methylation-specific polymerase chain reaction. RESULTS: One out of 29(3.4%) revealed hypermethylation of p16 in benign meningiomas. Atypical and malignant meningiomas showed hypermethylation of p16 in 2 out of 16 cases(12.5%) and in 5 out of 23 cases(21.7%), respectively. Immunohistochemical analysis of methylation-positive tumors demonstrated that tumor cells had reduced immunoreactivity compared to normal lymphocytes. CONCLUSIONS: Our results suggest that inactivation of p16 gene plays a role in the pathogenesis of meningioma and hypermethylation is one of the processes for gene inactivation.

Papillary Immature Metaplasia of the Uterine Cervix: a Report of 5 Cases with an Emphasis on the Differential Diagnosis from Reactive Squamous Metaplasia, High-Grade Squamous Intraepithelial Lesion and Papillary Squamous Cell Carcinoma

Papillary immature metaplasia (PIM) is a distinctive exophytic lesion of the uterine cervix and shares some histologic and cytologic features with ordinary squamous metaplasia (SM), atypical immature squamous metaplasia (AIM), high-grade squamous intraepithelial neoplasia (HSIL) and papillary squamous cell carcinoma (PSC). PIM has been suggested to be a subset of condyloma associated with low-risk type human papilloma virus (HPV), however, the etiologic role of HPV and biologic behavior of the disease are still elusive. We compared the clinical and histopathological findings, immunohistochemical expression of Ki-67 and p53 protein, and HPV typing of 5 cases of PIM with SM (n=9), HSIL (n=6), and PSC (n=4) to know the helpful features for the differential diagnosis. Histologically, all 5 cases showed a papillary proliferation of immature metaplastic cells involving the proximal transformation zone and endocervix. On HPV typing by polymerase chain reaction-restriction fragment length polymorphism, 2 out of 5 PIM were confirmed to have HPV 6 or HPV 11, while 2 out of 4 PSC were proved having HPV 31 and HPV 16 each. Ki-67 labeling index and mitotic index of PIM were significantly lower than those of HSIL or PSC. There were no significant differences of Ki-67 labeling index and mitotic index between PIM and SM. The expression of p53 varied among the groups and thus it was not helpful for the differential diagnosis.

Effects of Increased Lymphocytes and B Cell Clonality of Marrow Aspirates on Marrow Involvement and Prognosis in Children with Neuroblastoma / 대한혈액학회지

BACKGROUND: The lymphocytes including morphologically immature lymphoid cells are frequently increased in the marrow aspirates of children with neuroblastoma. We studied about the clonality of these lymphoid cells and its effects on the marrow involvement and prognosis of disease. METHODS: We evaluated 30 marrow aspirates of 23 children with neuroblastoma from 1990 to 1998. We tested the immunoglobulin heavy chain gene rearrangement PCR for B cell clonality and T cell receptor gamma gene rearrangement PCR for T cell clonality with bone marrow specimens. RESULTS: Younger children showed negative bone marrow involvement more than older children. In this group, the proportions of immature lymphoid cells and total lymphocytes were higher (3.4+/-3.2% vs. 0.8+/-1.9%, 31.3+/-17.0% vs. 14.7+/-12.0%). Immunoglobulin heavy chain gene rearrangements were present in 19/30 (64%) specimens and more frequently observed in negative marrow involvement cases. Seven cases with the proportions of total lymphocytes more than 30% showed significantly high long-term survival probability (P=0.05). Ten cases with B cell monoclonality showed the tendency of high long-term survival probability (P=0.13). CONCLUSION: The increase of lymphocytes including morphologically immature lymphoid cells in the marrow aspirates of children with neuroblastoma were frequently observed in the children without marrow involvement of malignancy and closely related to B cell clonality. The increase of total lymphocytes and related B cell monoclonality may be one of possible explanations of goodprognosis of children with neuroblastoma.